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Chemistry of Carbohydrates

Introduction

  • The most abundant heteropolysaccharides in the body.
  • Highly negatively charged molecules,with extended conformation that imparts high viscosity to the solution.
  • GAGs are located primarily on the surface of cells or in the extracellular matrix (ECM).
  • Along with the high viscosity of GAGs comes low compressibility, which makes these molecules ideal for a lubricating fluid in the joints.
  • Their rigidity provides structural integrity to cells and provides passageways between cells, allowing for cell migration.

GAGs of physiological significance

The specific GAGs of physiological significance are:

  • Hyaluronic acid,
  • Dermatan sulfate
  • Chondroitin sulfate
  • Heparin
  • Heparan sulfate, and
  • Keratan sulfate.

Chemistry

  • These molecules are long unbranched polysaccharides containing a repeating disaccharide unit. [acidic sugar-amino sugar]n
  • Although each of these GAGs has a predominant disaccharide component, heterogeneity does exist in the sugars present in the make-up of any given class of GAG.

Nature of amino sugars (figure-1)

The disaccharide units contain either of two modified amino sugars,

  • N-acetyl galactosamine (GalNAc) or
  • N-acetylglucosamine (GlcNAc),

Amino sugars

Figure-1- Amino sugars- β-D Glucosamine and β-D Galactosamine

The amino sugar may also be sulfated on carbon 4 or 6 or on non acetylated nitrogen.

Nature of acid sugar

Uronic acid represents acid sugar in the form of:

  • Glucuronate or
  • Iduronate

The acidic sugars contain carboxyl groups that are negatively charged at physiological pH, (figure-2) and together with the sulfate groups, give glycosaminoglycans their strongly negative nature.

Acid sugars

Figure-2- The acid sugars present in Glycosaminoglycans are D- Glucuronate and L- Iduronate.

Structure- function relationship

Because of their large number of negative charges, these heteropolysaccharides chains tend to be extended in solution. They repel each other and are surrounded by a shell of water molecules. When brought together they “slip” past each other. This produces the slippery consistency of mucous secretions and synovial fluid. When a solution of GAG is compressed, the water is squeezed out and GAGs are forced to occupy a smaller volume. When the compression is released the GAGs get back to their original, hydrated volume because of the repulsion of the negative charges. This property contributes to resilience of synovial fluid and vitreous humor of eye.

THE SPECIFIC GAGs OF PHYSIOLOGICAL SIGNIFICANCE ARE:

1) Hyaluronic acid – The repeating disaccharide unit is:

Glucuronic acid and N Acetylglucosamine (figure-3)

(D-Glucuronate + GlcNAc) n

Hyaluronic acid

Figure-3- structure of Hyaluronic acid

Occurrence:  Hyaluronic acid is found in –

  • Synovial fluid,
  • ECM of loose connective tissue, umbilical cord and vitreous humor of the eye.

Function

  • It serves as a lubricant and shock absorber.
  • It is the only GAG that is not limited to animal tissue but is also found in bacteria.
  • Hyaluronic acid is unique among the GAGs because it does not contain any sulfate and is not found covalently attached to proteins.
  • It forms non-covalently linked complexes with Proteoglycans in the ECM.
  • Hyaluronic acid polymers are very large (100 – 10,000 k Da) and can displace a large volume of water.

2) Dermatan sulfate- The repeating disaccharide unit is L-Iduronic acid and N-Acetyl Galactosamine with variable amount of Glucuronic acids (figure-4).

(L-Iduronate + GalNAc sulfate) n

 Dermatan sulfate

Figure-4- structure of Dermatan Sulfate

Occurrence:  It is found in skin, blood vessels and heart valves

3) Chondroitin sulfate- The repeating disaccharide unit is Glucuronic acid and N-Acetyl galactosamine with sulfate on either C-4 or C-6. Based on presence of sulfate group, it may be labeled as Chondroitin-4-Sulfate or Chondroitin-6-Sulfate (figure-5).

(D-Glucuronate + GalNAc sulfate) n

Chondroitin sulfate

Figure-5-Structure of Chondroitin Sulfate

Occurrence:  It is found in cartilages, tendons, ligaments, heart valves and aorta.

Function

It is the most abundant GAG. In cartilages it binds collagen and holds fibers in a tight, strong network.

4) Heparin sulfate – The repeating disaccharide unit is:

L-Iduronic acid and D- Glucosamine with variable amounts of Glucuronic acid. Most glucosamine residues are bound in Sulfamide linkages (figure-6). Sulfate is also found on C-3 or C-6 of Glucosamine and C-2 of uronic acid (An average of 2.5 Sulfate per disaccharide unit)

(D-Glucuronate sulfate +N-Sulfo-D-glucosamine) n

Heparin sulfate

Figure-6- structure of Heparin Sulfate

Occurrence: Heparin is a component of intracellular granules of mast cells lining the arteries of the lungs, liver and skin (contrary to other GAGs that are extra cellular compounds, it is intracellular).

Function– It serves as an anticoagulant.

5) Heparan sulfate: Heparans have less sulfate groups than heparins. The repeating disaccharide unit is same as Heparin. Some Glucosamines are acetylated

Occurrence- It is an extracellular GAG found in basement membrane and as a ubiquitous component of cell surfaces

6) Keratan sulfate –The repeating disaccharide unit is galactose and N-Acetyl glucosamine (No uronic acid). The sulfate content is variable and may be present on C-6 of either sugar (figure-7).

(Gal + GlcNAc sulfate) n

Keratan sulfate

Figure-7- Structure of Keratan sulfate

Occurrence:  cornea, bone, cartilage; Keratan sulfates are often aggregated with Chondroitin sulfates.

Proteoglycans (mucoproteins) 

Proteoglycans are formed of glycosaminoglycans (GAGs) covalently attached to the core proteins. They are found in all connective tissues, extracellular matrix (ECM) and on the surfaces of many cell types. Proteoglycans are remarkable for their diversity (different cores, different numbers of GAGs with various lengths and compositions).

Structure of Proteoglycans

All of the GAGs, except Hyaluronic acid are found covalently attached to protein forming proteoglycan monomers.

Structure of Proteoglycan monomer

A Proteoglycan monomer found in cartilage consists of a core protein to which the linear GAG chains are covalently linked. These chains which each may be composed of more than 100 monosaccharides extend out from the core protein and remain separated from each other because of charge repulsion. The resulting structure resembles a ‘Bottle brush’ (figure-8). In cartilage proteoglycans, the species of glycosaminoglycans include Chondroitin sulfate and Keratan sulfate.

 

Proteoglycan polymer

Figure-8- structure of Proteoglycan monomer (Bottle Brush)

 Linkage between the carbohydrate chain and the protein

The linkage of GAGs such as (heparan sulfates and Chondroitin sulfates) to the protein core involves a specific trisaccharide linker (Galactose-galactose-Xylose). The protein cores of Proteoglycans are rich in Serine and Threonine residues which allow multiple GAG attachments.

An O-Glycosidic bond is formed between the Xylose and the hydroxyl group of Serine. Some forms of Keratan sulfates are linked to the protein core through an N-asparaginyl bond (N-Glycosidic linkage)

Proteoglycan Aggregates- The proteoglycan monomers associate with a molecule of Hyaluronic acid to form Proteoglycan aggregates (figure-9). The association is not covalent, but occurs primarily through ionic interactions between the core protein and Hyaluronic acid. The association is stabilized by additional small proteins called Link proteins.

Proteoglycan aggregate

Figure-9- structure of proteoglycan aggregate

Functions of Proteoglycans

They perform numerous vital functions within the body.

GAG dependent functions can be divided into two classes: the biophysical and the biochemical.

1) The biophysical functions depend on the unique properties of GAGs: the ability to fill the space, bind and organize water molecules and repel negatively charged molecules. Because of high viscosity and low compressibility they are ideal for a lubricating fluid in the joints. On the other hand their rigidity provides structural integrity to the cells and allows the cell migration due to providing the passageways between cells.

2) The other, more biochemical functions of GAGs are mediated by specific binding of GAGs to other macromolecules, mostly proteins. Proteoglycans participate in cell and tissue development and physiology.

3) Heparin acts as an anticoagulant and is used in the clinical practice.

 

 

 

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A 7-month-old baby girl, the second child born to unrelated parents was brought to Pediatrics outdoor department. History revealed that she did not respond well to breast-feeding and was changed entirely to a formula based on cow’s milk at 4 weeks. Between 7 and 12 weeks of age, she was admitted to the hospital twice with a history of screaming after feeding, but was discharged after observation without a specific diagnosis. Elimination of cow’s milk from her diet did not relieve her symptoms; her mother reported that the screaming bouts were worse after the child drank juice and that she frequently had gas and a distended abdomen. The child was diagnosed having ‘Hereditary fructose intolerance’. The mother of the child was instructed to eliminate fructose containing foods from the child’s diet and was strictly instructed to feed milk without table sugar. The table sugar (sucrose), a disaccharide, contains glucose and fructose linked as:

A. O-α-D-glucopyranosyl-(1->6)-α -D- fructofuranoside

B. O-β-D-glucopyranosyl-(1->6)-α -D- fructofuranoside

C. O-α-D-glucopyranosyl-(1->2)-β -D-fructofuranoside

D. O-α-D-glucopyranosyl-(1->2)-α -D-fructofuranoside

E. None of the above.

The correct answer is C- O-α D-glucopyranosyl-(1->2)-β -D-fructofuranoside. The onset of symptoms after ingestion of juice (fructose or fructose containing diet) is a sign of hereditary fructose Intolerance’.

Hereditary fructose intolerance is caused by deficiency of Aldolase B, the enzyme required for the metabolism of fructose. These patients are healthy and asymptomatic until fructose or sucrose (table sugar) is ingested (usually from fruit, sweetened cereal, or sucrose-containing formula). Elimination of dietary fructose is both a compulsory and therapeutic step.

In patients who are ill, elimination may also serve as a diagnostic test because all symptoms should completely resolve. With this treatment, as the patient matures, symptoms become milder, even after fructose ingestion, and the long-term prognosis is good.

Table sugar (sucrose) is a source of fructose and in Sucrose, the anomeric carbon atoms of a glucose unit and a fructose unit are joined; the configuration of this glycosidic linkage is α-for glucose and β-for fructose (figure).

 

Structure of sucrose

Figure- Structure of sucrose

Sucrose can be cleaved into its component monosaccharides by the enzyme sucrase.

An overview of properties of sucrose

  • Sucrose has no free reactive group because the anomeric carbons of both monosaccharides units are involved in the glycosidic bond. Therefore, sucrose neither shows reducing nor mutarotation characters.
  • Sucrose is called invert sugar because the optical activity of sucrose (dextrorotatory) is inverted after hydrolysis (by an acid or an enzyme (invertase or sucrase) into an equimolar mixture of its two components glucose (+52.5) and fructose (-92.5) and the optical activity of the mixture becomes levorotatory.  

 

 

 

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Glycogen, Starch and Inulin are storage polysaccharides.

1) Glycogen 

  • Glycogen is a readily mobilized storage form of glucose.
  • It is a very large, branched polymer of glucose residues (Figure-1) that can be broken down to yield glucose molecules when energy is needed.
  • Most of the glucose residues in glycogen are linked by α-1,4-glycosidic bonds.
  • Branches at about every eighth to tenth residue are created by α-1,6-glycosidic bonds.
  • It is the storage polysaccharide in animals and is sometimes called, ‘Animal starch’, but it is more branched than amylopectin present in starch.

Glycogen structure

Figure- 1- The structure of glycogen, the branch point is created by α-1,6-glycosidic linkage 

  • It is hydrolyzed by both α and β-amylases and by glycogen phosphorylase. The complete hydrolysis yields glucose.
  • Glycogen on reaction with iodine gives a reddish-brown color.
  • Glycogen is stored in muscle and liver. The concentration of glycogen is higher in the liver than in muscle (10%versus 2% by weight), but more glycogen is stored in skeletal muscle overall because of its much greater mass.
  • Glycogen is present in the cytosol in the form of granules ranging in diameter from 10 to 40 nm.
  • In the liver, glycogen synthesis and degradation are regulated to maintain blood-glucose levels as required to meet the needs of the organism as a whole. In contrast, in muscle,these processes are regulated to meet the energy needs of the muscle itself.

Glycogen is not as reduced as fatty acids are and consequently not as energy rich, but still animals store energy as glycogen?

All excess fuel is not converted to fatty acids. Glycogen is an important fuel reserve for several reasons:

  • The controlled breakdown of glycogen and release of glucose increase the amount of glucose that is available between meals. Hence, glycogen serves as a buffer to maintain blood-glucose levels.
  • Glycogen’s role in maintaining blood glucose levels is especially important because glucose is virtually the only fuel used by the brain, except during prolonged starvation.
  • Moreover, the glucose from glycogen is readily mobilized and is therefore a good source of energy for sudden,strenuous activity. Unlike fatty acids, the released glucose can provide energy in the absence of oxygen and can thus supply energy for anaerobic activity.

2) Starch

  •  It is a polymer of glucose, found in roots, rhizomes, seeds, stems, tubers and corms of plants, as microscopic granules having characteristic shapes and sizes.
  • Most animals,including humans, depend on these plant starches for nourishment.
  • The intact granules are insoluble in cold water, but grinding or swelling them in warm water causes them to burst. The released starch consists of two fractions.
  • About 20% is a water-soluble material called Amylose.
  • The majority of the starch is a much higher molecular weight substance, consisting of nearly a million glucose units, and called amylopectin.

(a) Amylose

  • It is a linear polymer of α-D-glucose, linked together by α 1→4 glycosidic linkages.
  • It is soluble in water,reacts with iodine to give a blue color and
  • The molecular weight of Amylose ranges between 50, 000 – 200, 000.

Structure of Amylose

 Figure-2- Structure of Amylose

(b) Amylopectin 

  • It is a highly branched polymer,insoluble in water, reacts with iodine to give a reddish violet color.
  • The molecular weight ranges between 70, 000 – 1 000, 000.
  • Branches are composed of 25-30 glucose units linked by α 1→4 glycosidic linkage in the chain and by α 1→6 glycosidic linkage at the branch point.

 Amylopectin

Figure-3 – Structure of Amylopectin

Hydrolysis: Hydrolysis of starch with hot dilute acids or by enzymes gives dextrins of varying complexities, maltose and finally D-glucose

3) Inulin

  • Inulin is a polysaccharide of fructose (and hence a fructosan) found in tubers and roots of dahlias, artichokes, and dandelions.
  • It is readily soluble in water and is not hydrolysed by intestinal enzymes.
  • It has a lower molecular weight than starch and colors yellow with iodine.
  • It is used to determine the glomerular filtration rate, Inulin is of particular use as it is not secreted or reabsorbed in any appreciable amount at the nephron allowing GFR to be calculated, rather than total renal filtration. However, due to clinical limitations, Inulin is rarely used for this purpose and creatinine values are the standard for determining an approximate GFR.

 

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Representation of ring structure of monosaccharides

The ring structures of monosaccharides can be represented as follows :

1) Fischer projection

The acyclic structure of a sugar is commonly shown by using a Fischer projection. A Fischer projection is sometimes used to illustrate the cyclic hemiacetal form of a sugar. The presence of an aldehyde group and the hydroxyl groups in an aldose make it possible for these compounds to undergo intramolecular reactions to form cyclic hemiacetal. These cyclic hemiacetals, are often more stable than is the open-chain form of the sugar. The ketoses (keto group containing sugars) form hemiketal rings

 Hemiacetal

Figure-1- In Fischer projection, α anomer has the orientation of OH towards the right side, whereas, in beta anomer, it is towards the left side.

2) Haworth projection

Rules for drawing Haworth projections

Either a six or 5-membered ring is drawn including oxygen as one atom.
Most aldohexoses are six-membered resembling Pyran- an organic compound having a 6 membered ring (Figure-2).
Aldotetroses, aldopentoses, ketohexoses are 5-membered resembling Furan- A five membered organic compound (Figure-2)

 Furan and Pyran

Figure-2- Structure of Furan and Pyran.

Numbering the rings

The numbering is done clockwise starting next to the oxygen (Figure-3)

 Numbering the rings

Figure-3- Numbering the rings

Pyranose and Furanose forms of Glucose (Figure-4)

 Pyranose and furanose forms

Figure-4- Glucopyranose and Glucofuranose forms

In Haworth configuration all groups to the right of carbon backbone in Fischer projection are oriented down (down -right) while all groups to the left of carbon backbone are oriented up, except those around C5,the reverse orientation occurs (Figure-5).

 Alpha and beta anomers (Figure-5)

 Anomers

Figure-5- When drawn in the Haworth projection, the α configuration places the hydroxyl downward, while the β is the reverse.

Mutarotation

Carbohydrates can change spontaneously between α and β configurations through intermediate open chain formation, this leads to a process known as Mutarotation. There is gradual change in optical rotation of the solution. The initial optical rotation is changed to a constant optical rotation characteristic of that sugar.

This can be explained in reference to two experiments

1) When D Glucose is crystallized at room temperature and a fresh solution is prepared, its specific rotation of polarized light is +112ο, but after 12-18 hours it changes to +52.5 ο

2) If the initial crystallization takes place at 98 ο and then solubilized, the specific rotation is found to be +19 ο, which also changes to +52.5 ο within a few hours.

This change in rotation with time is called Mutarotation.

Explanation

At room temperature the alpha form predominates and the specific rotation is+112ο, there is transient ring opening and change in configuration. In the second condition when the crystallization takes place at 98 ο, the Beta form predominates and the specific rotation is+19 ο. Both undergo Mutarotation and at equilibrium one-third molecules are α type and two third are β variety to get the specific rotation of+52.5 ο (Figure-6) . 

 Mutarotation

 Figure-6- Mutarotation of Glucose

 The constant specific rotation is due to the resultant net optical activity of both alpha and beta anomers.

 

 

 

 

 

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Isomerism in monosaccharides

The monosaccharides having asymmetric carbon atoms exhibit isomerism.

Asymmetric carbon atom- It is the carbon atom that is attached to four different groups (Figure-1)

 asymmetric carbon

Figure-1- An asymmetric carbon atom with 4 different attachments

All monosaccharides except- Dihydroxy acetone, have asymmetric carbon atoms (Figure-2)

 Glyceraldehyde and DHA

Figure-2- Glyceraldehyde has an asymmetric carbon atom whereas dihydroxyacetone lacks, thus it does not have isomers.

Based on the presence of asymmetric carbon atoms the following types of isomerism of monosaccharides are observed in the human system-

1) D and L isomerism- The orientation of the —H and —OH groups around the carbon atom adjacent to the terminal primary alcohol carbon (carbon 5 in glucose) determines whether the sugar belongs to the D or L series. When the —OH group on this carbon is on the right (as seen in figure-3), the sugar is the D isomer; when it is on the left, it is the L isomer (figure-3)

 D-L-glucose

Figure-3- D and L isomers of Glucose

Glyceraldehyde has a single asymmetric carbon and, thus, there are two stereoisomers of this sugar.

D-Glyceraldehyde and L-glyceraldehyde . The D and L isomers of monosaccharides are called enantiomers, as they are mirror images of each other (Figure-4)

 D and L isomers of glyceraldehyde

Figure-4- D and L Isomers of Glyceraldehyde

Biological significance

  • Most of the monosaccharides occurring in mammals are D sugars, and the enzymes responsible for their metabolism are specific for this configuration.
  • D-Ribose, the carbohydrate component of RNA, is a five-carbon aldose.
  • D-Glucose, D-mannose, and D -galactose are abundant six-carbon aldoses.
  • Some sugars naturally occur in the L form e.g. L-Arabinose and L-Fucose are found in glycoproteins.

2) Optical Isomerism- The presence of asymmetric carbon atoms also confers optical activity on the compound. When a beam of plane-polarized light is passed through a solution of an optical isomer, it rotates either to the right, dextrorotatory (+), or to the left, levorotatory (–). The direction of rotation of polarized light is independent of the stereochemistry of the sugar, so it may be designated D (–), D (+), L (–), or L (+) – figure-5

For example, the naturally occurring form of fructose is the D (–) isomer. In solution, glucose is dextrorotatory, and glucose solutions are sometimes known as dextrose.

Measurement of optical activity in chiral or asymmetric molecules using plane polarized light is called Polarimetry. The measurement of optical activity is done by an instrument called Polarimeter.

 Optical activity

Figure-5- Rotation of polarized light by an optically active solution

3) Epimers

The compounds with the same molecular formula, but differing in spatial configuration of the attached groups around a single carbon atomonly are called epimers. 

In hexoses, isomers differing as a result of variations in configuration of the —OH and —H on carbon atoms 2, 3, and 4 are known as epimers. Biologically, the most important epimers of glucose are mannose and galactose, formed by epimerization at carbons 2(figure-6) and 4(figure-7), respectively.  

 C2 epimers

Figure-6- Glucose and Mannose are C2 epimers.

 C4 epimers

Figure-7- Glucose and galactose are C4 epimers

Mannose and Galactose are not epimers of each other as they differ in configuration around 2 carbon atoms (figure-8).

 C2 and C4 epimers

Figure-8- Relationship of glucose, galactose and mannose

 4) Aldose-ketose isomerism

Compounds with the same molecular formula but differing in nature of functional group (aldehyde or keto) are aldose ketose isomers.

 Examples- Fructose and Glucose are aldose ketose isomers.

Aldose keotse isomers

Figure-9- Aldose ketose isomers (D-Glucose and D-Fructose)

Fructose has the same molecular formula as glucose but it differs in its structural formula, since there is a potential keto group in position 2, the anomeric carbon of fructose (Figure-9), whereas there is a potential aldehyde group in position 1, the anomeric carbon of glucose.

Glyceraldehyde and Dihydroxyacetone, Ribose and Ribulose are other examples of aldose -ketose isomers.

5) Anomers

In biological system the monosaccharides tend to exist in a ring form. The ring structure of an aldose is a hemiacetal, since it is formed by combination of an aldehyde (C1) and an alcohol group (Mostly C5). Similarly, the ring structure of a ketose is a hemiketal.  The ring can open and reclose allowing the rotation to occur around the carbon bearing the reactive carbonyl group yielding two possible configurations- α and β of the hemiacetal and hemiketal. The carbon about which this rotation occurs is called Anomeric carbon and the two stereoisomers are called Anomers. In alpha anomer the orientation of the OH group is towards the right side whereas in the beta anomer, it is towards the left side. (Figure-10).

 

 alpha and beta anomers

Figure-10- Alpha and beta anomers of glucose

When drawn in the Haworth projection, the α configuration places the hydroxyl downward. While the β is the reverse (figure-11).

 Haworth projections

Figure-11- Alpha and beta anomers of glucose drawn in Haworth projection

 

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 General Introduction

  • Carbohydrates are the most abundant compounds found in nature (cellulose: 100 billion tons annually)
  • They make up most of the organic matter on earth because of their extensive roles in all forms of life.
  • One of the four major classes of biomolecules along with proteins, nucleic acids and lipids.
  • The term carbohydrate is derived from the French  term : hydrate de carbone, they are hydrates of carbon
  • Compounds composed of C, H, and O
  • Empirical formula (CH2O)n , for example when n = 5 then C5H10O5
  • Not all carbohydrates have this empirical formula: e.g. sugar derivatives deoxysugars, amino sugars etc., do not follow this rule.

General characteristics

  • They have  large number of hydroxyl groups (poly hydroxy)- Figure-1-a
  • In addition they may contain-an aldehyde group (polyhydroxy aldehydes) or a keto group (polyhydroxy ketones)- Figure-1-b
  • Their derivatives may also contain nitrogen, phosphorus or sulfur- Figure-1-c

 Polyhydroxy compounds

Figure-1-a)  Carbohydrates are derivatives of polyhydroxy aldehyde or ketone compounds

Aldehyde

b)  Aldehyde derivative  

Keto group

c) Ketone derivative

Functions of Carbohydrates

1) Sources of energy, especially for brain and red blood cells.

2) Intermediates in the biosynthesis of other basic biomolecules (lipids and proteins)

3) Associated with other entities such as glycosides, vitamins and antibiotics

4) Ribose and deoxyribose sugars form part of the structural framework of RNA and DNA.

4) Form structural tissues in plants and in microorganisms

5) Carbohydrates are linked to many proteins and lipids, where they play key roles in mediating interactions among cells and interactions between cells and other elements in the cellular environment.

Classification of carbohydrates

1) Monosaccharides (monoses or glycoses)
Trioses, Tetroses, Pentoses, Hexoses

2) Oligosaccharides
Di, tri, tetra, penta, up to 9 or 10
Most important are the disaccharides

3) Polysaccharides or glycans
a) Homo polysaccharides
b) Heteropolysaccharides

Monosaccharides

  • Also known as simple sugars
  • Cannot be hydrolyzed further
  • Classified  either by the number of carbon atoms or by the nature of functional group-aldoses or ketoses
  • Most  of the carbohydrates (99%) are straight chain compounds
  • D-glyceraldehyde is the simplest of the aldoses (aldotriose), all other sugars have the ending -ose (glucose, galactose, ribose, lactose, etc.)
  • Keto group containing monosaccharides have the ending-ulose (Xylulose, ribulose, erythrulose), except dihydroxyacetone

MONOSACCHARIDES – Classification

1-According to number of carbons they contain in their backbone structures-
 It is a variable prefix followed by the suffix (-ose)

  • Trioses=3 Carbon,
  • Tetroses=4C,
  • Pentoses=5C,
  • Hexoses=6C,
  • Heptoses=7C

 2- According to nature of reactive group – depending on the presence of Aldehyde or keto group.Aldose sugars e.g. glyceraldehyde (figure-2-a)

  • Aldose sugars e.g. glyceraldehyde (figure-2-a)
  • A ketose sugars e.g. dihydroxyacetone (figure-2-b)

 Glyceraldehyde

Figure-2)-a) Glyceraldehyde-  An Aldotriose                          

Dihydroxy acetone

b) Dihydroxy acetone- A ketotriose

 Details of classification

Number of carbon atoms Aldose Ketose
3 (Trioses) Glyceraldehyde Dihydroxyacetone
4(Tetroses) Erythrose Erythrulose
5 (Pentoses) Ribose, Arabinose, Xylose Ribulose, Xylulose
6 (Hexoses) Glucose, Galactose, Mannose Fructose
7(Heptoses) Sedoheptulose

 Biological significance of monosaccharides

  • Monosaccharides are important fuel molecules as well as building blocks of nucleic acids.
  • Trioses- Glyceraldehyde and dihydroxyacetone, in their phosphorylated forms are intermediates of glycolysis.
  • Tetroses are intermediates of HMP (Hexose mono phosphate) pathway, which is an intermediate pathway of glucose utilization
  • Pentoses form the structural components of glycoproteins, nucleotides and nucleic acids. They also serve as intermediates in the HMP pathway.
  • Hexoses
    • Glucose is an important fuel molecule, preferred source of energy for the brain cells and the only source of energy for the red blood cells and the cells lacking mitochondria.
    • Fructose- component of table sugar(Sucrose), honey and source of energy for the spermatozoa
    • Galactose- An important component of milk sugar (Lactose)
    • Mannose- An important component of glycoproteins.
    • Heptoses- Sedoheptulose is an important intermediate of HMP pathway
    • Nonoses- Sialic acid is an important component of glycolipids.
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Q.1- Which of the following is not a disaccharide?

a) Hyaluronic acid                                            

b) Maltose

c) Lactose                                           

d) Sucrose                                                          

Q.2- What is the molecular formula of Glucose?

a) CH3OH                                            

b) C12H22O11

c) C6H1206                                                            

d)  C6H12O5                                           

Q.3-Sucrose is composed of which two sugars?

a) Glucose and Glucose                                

b) Glucose and Fructose

c) Glucose and Galactose                            

d) Fructose and Galactose                            

Q.4- In which of the following forms Glucose is stored in plants?

a) Starch                                             

b) Dextrins

c) Glycogen                                        

d) Cellulose                                         

Q.5-Which out of the following is a Carbohydrate with no nutritional value?

a) Glycogen                                       

b) Starch

c) Dextrin                                                           

d) Cellulose                                                         

Q.6- Choose a sugar out of the following that is non reactive to Seliwanoff reagent?

a) Sucrose                                          

b) Fructose

c) Inulin                                                                               

d) Ribose                                                              

Q.7- Choose a keto triose-

a) Glyceraldehyde                                          

b) Dihydroxyacetone

c) Erythrose                                                       

d) Arabinose                                                       

Q.8- A pentose sugar present in the heart muscle is-

a) Xylose                                            

b) Xylulose

c) Lyxose                                           

d) Aldose                                               

Q.9- d -Glucose and l- Glucose are-

a)Stereo isomers                                         

b)Anomers

c) Keto- Aldose Isomers                               

d) Optical isomers                                             

Q.10- All the following tests are positive for Lactose except-

a) Benedict                                                        

b) Barfoed

c) Molisch                                                           

d) Osazone                                          

Q.11- Glucose can have — isomers due to the presence of 4 asymmetric carbon atoms-

a) 4                                                                          

b) 2

c) 12                                                 

d) 16                                                       

Q.12- Fructose and Ribulose are-

a) Epimers                                                          

b) Anomers

c) Ketoses                                           

d) Ketose- Aldose isomers                             

Q.13- The compounds having same structural formula but differing in configuration around one carbon atom are called-

a) Optical isomers                                           

b) Anomers

c) Stereo isomers                                            

d) Epimers                                           

Q.14- What does the following equation represent?

α-D Glucose +112ο→+52.5 ο →  +19 ο β- D glucose

a) Stereoisomerism                                       

b) Optical isomerism

c) Mutarotation                                               

d) Epimerization                                                

Q.15- The carbohydrate of honey is

a) Fucose                                            

b) Maltose

c) Lactose                                             

d) Fructose                                                          

Q.16- Mannonic acid is a-

a) Sugar acid                                                      

b) Deoxy sugar     

c) Amino sugar                                                 

d) Sugar alcohol                                                 

Q.17- Which of the following is not a monosaccharide with 5 carbon atoms?

a) Arabinose                                                     

b) Trehalose

c) Xylulose                                                         

d) Ribulose                                          

Q.18- Which of the following gives a brown color on reaction with iodine?

a) Starch                                            

b) Glycogen

c) Dextrin                                          

d) Cellulose                                         

Q.19-Invert sugar is-

a) Starch                                            

b) Fructose

c) Glucose                                          

d) Hydrolytic product of Sucrose              

Q.20- Which out of the following is a structural homopolysaccharide?

a) Hyaluronic acid                                              

b) Chitin

c) Inulin                                                 

d) Starch                               

 

Key to Answers

1) -a,  2)-c, 3)-b, 4)-a, 5) -d, 6)- d, 7)- b, 8)-c, 9)-d, 10)- b,11) -d, 12)-c, 13)-d, 14)- c,15)-d, 16)-a,17)-b, 18)- b, 19)- d, 20)- b.

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Q.1- Which of the following is a non reducing disaccharide?

a) Galactose                                                                      

b) Maltose

c) Trehalose                                                                      

d) Sucrose                                             

Q.2- Which of the following is a true statement about glucose?

a) It cannot be utilized by red blood cells

b) It has 4 asymmetric carbon atoms

c) It is stored as starch in animals

d) It is oxidized to form glycerol                                                                                                

Q.3-Sucrose is composed of which of the following two sugars?

a) Glucose and Glucose                                                

b) Glucose and Fructose

c) Glucose and Galactose                                            

d) Fructose and Galactose            

Q.4- Which of the following is not a homopolysaccharide?

a) Starch                                                             

b) Heparin

c) Glycogen                                                       

d) Cellulose                     

Q.5-Which out of the following is a fructosan?

a) Glycogen                                                                       

b) Agar

c) Inulin                                                               

d) Cellulose                                         

 Q.6- Choose a sugar abundantly present in honey-

a) Maltose                                                          

b) Fructose

c) Ribulose                                                         

d) Lactose                                          

Q.7- Choose an Aldo pentose-

a) Glyceraldehyde                                                          

b) Dihydroxyacetone

c) Erythrose                                                                       

d) Arabinose                                     

Q.8- Which of the following is a keto tetrose?

a) Xylose                                                             

b) Erythrulose

c) Fructose                                                                         

d) Sedoheptulose                            

Q.9- α –D-Glucose and β-D- Glucose are-

a) Stereo isomers                                                            

b) Anomers

c) Keto- Aldose Isomers                                               

d) Optical isomers                             

Q.10- All tests are positive for Lactose except-

a) Benedict                                                                        

b) Barfoed

c) Molisch                                                                           

d) Osazone                                          

Q.11- Which out of the following is a carbohydrate with 6 carbon atoms and a keto group as the functional group?

a) Glyceraldehyde                                                          

b) Dihydroxy acetone

c) Fructose                                                                         

d) Galactose                      

Q.12- Mucic acid and Gluconic acids are

a) Glycosides                                                                     

b) Sugar acids

c) Amino sugar acids                                                      

 d) Sugar alcohols                            

Q.13- Sorbitol and Mannitol are-

a) Optical isomers                                                           

b) Anomers

c) Stereo isomers                                                            

d) Epimers                                           

Q.14- Which of the following tests is not based on the reaction of carbohydrates with strong acids?

a)Molisch                                                                           

b) Benedict’s

c) Bial’s                                                                                 

d) Seliwanoff’s                 

Q.15- Which out of the following does not form osazone crystals?

a)Galactose                                                                       

b) Maltose

c) Lactose                                                                           

d) Sucrose                           

Q.16- N- Acetyl Neuraminic acid is a-

a) Sugar acid                                                                      

b) Amino sugar acid

c) Amino sugar                                                                 

d) Sugar alcohol                                 

Q.17- Which of the following gives a negative reaction with Barfoed’s test

a) Glucose                                                                          

b) Maltose

c) Erythrose                                                                       

d) Fructose                                        

Q.18- A polysaccharide formed by β1→4 Glycosidic linkages between glucose residues is

a) Inulin                                                                                               

b) Amylose

c) Agar                                                                                  

d) Cellulose                                          

Q.19- Which of the following sugars is laevorotatory predominantly?

a) Starch                                                             

b) Fructose

c) Sucrose                                                                          

d) Glucose                                                                                                                                                                         

Q.20- Which of the following Mucopolysaccharides is non sulfated and most abundant in tissues?

 a) Hyaluronic acid                                                           

b) Keratan sulphate

c) Heparin                                                          

d) Dermatan sulphate   

 Key to answers

1)-c, 2)-b, 3)-b, 4)-b, 5)- c, 6)-b, 7)-d, 8)-b, 9)-b, 10)-b, 11)-c,12)-b, 13)-d, 14)-b, 15)-d, 16)-b, 17)-b, 18)-d,19)b, 20)-a .      

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Dietary fiber is indigestible part of plant foods that makes stool soft and thus enables smooth bowel movements, prevents constipation, hemorrhoids and diverticulosis. 

It consists of all of the components of the cell walls of plants that are not broken down by the body’s digestive enzymes.

Dietary Fiber and Total Fiber

“Dietary fiber” as noted on the “Nutrition Facts Label” of commercial foods, is fiber originally present in the food. “Total fiber” consists of dietary fiber and added fiber – substances that are adding to original food to increase their fiber content or to change their physical properties. Pectin, for example, is added to jam to give it a gel form.

Dietary fiber can be grouped into two main categories, those that are soluble and those that are insoluble in water.

Soluble Fiber

Soluble fiber (viscous fiber) partly dissolves in water and forms gel with it. Foods rich in soluble fiber include beans and other legumes (peas, soy, and lentils), oats, barley, citrus fruits (oranges, grapefruit), psyllium husk and flax seedSubstances found in soluble fiber are gum, pectin, some hemicelluloses, mucilage and storage polysaccharides (starch and glycogen).

Beneficial Effects of Soluble Fiber

  • Soluble fiber may prevent both diarrhea and constipation. It absorbs water from the gut and thus makes stool soft, but not bulky.
  • Soluble fiber may help in weight loss. It slows down the speed of the passage of food through the gut thus giving a feeling of fullness.
  • Soluble fiber may help to prevent and treat diabetes type 2. It slows down absorption of glucose from the intestine into the blood thus preventing high spikes of glucose in the blood after a meal.
  • Soluble fiber may lower total and LDL cholesterol and thus helps to prevent ischemic heart disease and stroke. It binds bile acids in the bowel and removes them from the body and thus reduces their absorption into the blood. Lost bile acids are replaced by synthesis from blood cholesterol. This is one theory about how soluble fiber lowers blood cholesterol levels.
  • Soluble fiber may prevent bile salt diarrhea after a gallbladder removal.   

Unwanted Effects of Soluble Fiber

Soluble fiber, if ingested in excess may cause:

  • Abdominal bloating and flatulence
  • Dehydration, if ingested without water
  • Pectin may reduce absorption of cholesterol-lowering drugs, like Lovastatin

Soluble Fiber Supplements

Examples of soluble fiber supplements:

  • Metamucil (psyllium – isphagula)
  • Citrucel (methylcellulose)
  • Benefiber (wheat dextrin)
  • FiberChoise (Inulin)
  • Pectin

The soluble fibers such as pectin and true plant gums are mucilaginous and are digestible.

Pectins are predominantly polygalacturonic acids with varying amounts of other hexose or pentose residues.

True plant gums are complex poly saccharides composed of primarily arabinose, fucose, galactose, mannose, rhamnose, and xylose. The gums are soluble in water and are digestible by the enzymes in the intestinal tract. Both pectins and gums are mucilaginous; they absorb water to form viscous gels in the stomach that decrease the rate of gastric emptying. The mucilaginous nature of the soluble fibers, pectins, and gums tends to decrease the rate at which carbohydrates are digested and absorbed, thus decreasing both the rise in blood glucose levels and the ensuing increase in insulin concentration.

Insoluble Fiber

Insoluble fiber can not be dissolved in water. Foods rich in insoluble fiber include whole wheat and other whole grains and most dark green leafy vegetables, like cabbage and cauliflower. Substances found in insoluble fiber include cellulose, hemicellulose and lignin.

Beneficial Effects of Insoluble Fiber

  • Insoluble fiber may help to prevent constipation, hemorrhoids and diverticulosis. It binds water and thus makes stool soft and bulky; it also speeds up the passage of food through the intestine.

Unwanted Effects of Insoluble Fiber

  • Ingesting foods with insoluble fiber containing sulphur (garlic, onions) may result in excessive gas.
  • Insoluble fiber eaten on an empty stomach may aggravate symptoms of irritable bowel syndrome.
  • Insoluble fiber ingested without water may result in severe constipation or even intestinal obstruction.
  • Certain types of insoluble fiber may trigger diarrhea in sensitive people.
  • Excessive ingestion of supplements containing insoluble fiber, especially in small children, may reduce absorption of calcium, magnesium, iron, copper and zinc.

1) Cellulose is a major structural component of plant cell walls. Cellulose is a long, linear polymer of glucose (β-D-glucopyranose) units that are joined by β(1→4) glycosidic bonds . Cellulose molecules have an extended, rigid structure that is stabilized by interchain hydrogen bonds.

Starch, the plant storage polysaccharide, which is also a polymer of glucose, differs in its structure in that the glucose monomer units are joined by α(1→4) glycosidic bonds .Starch is composed of two types of polymers, amylose, which has a nonbranched helical structure, and amylopectin, which is branched with α(1→6) glycosidic bonds joining the branches to the main polymer chain. Although starch is easily digested by salivary and pancreatic amylase and the disaccharidases present on the brush border of intestinal mucosal cells, cellulose cannot be hydrolyzed. The β(1→4) glycosidic bonds of the cellulose chain cannot be cleaved by the amylases present in the digestive tract.

 

 Figure -1- Showing the molecular structure of cellulose, indicating the repeating disaccharide unit, cellobiose.

 

 

Figure- 2-The molecular structure of starch, indicating the repeating disaccharide unit, maltose, as well as the α-1,6-glycosidic bond present in the branch points of amylopectin.

2) Hemicelluloses are also polysaccharides that are structural components of plant cell walls. However, unlike what their name implies, they are unrelated to cellulose. They are polymers that are made up of a variety of sugar monomers that include glucose, galactose, mannose, arabinose, and xylose, as well as acidic forms of these monosaccharides. Xylose is the monosaccharide that is most abundant. Hemicelluloses have a random, amorphous structure that is suitable for their location in the plant cell wall matrix. Depending on their molecular structure, hemicelluloses are partially digestible.

 3) Lignins are formed by the irreversible dehydration of sugars that result in aromatic structures. The remaining alcohol or phenol OH groups can react with each other and with aldehyde and ketone groups to form polymers. These polymers cannot be broken down by the digestive enzymes and, like cellulose and the indigestible portion of hemicelluloses, form the stool bulk.

 

Figure-3-  A lignin molecule in an early stage of condensation. The aromatic rings are a result of irreversible dehydration of sugar residues.

Although cellulose and hemicellulose are insoluble, they absorb water to swell and increase the stool bulk. This results in larger, softer stools. It has been shown that diets plentiful in insoluble fiber also increase the transit time of food in the digestive tract and decrease intracolonic pressure. Lignins, in addition to increasing stool bulk, also bind organic molecules such as cholesterol and many potential carcinogens. 

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Lyxose

Lyxose is a constituent of lyxoflavin isolated from human heart muscle. It is a monosaccharide containing 5 carbon atoms. D- Lyxose is present in nucleic acids of yeast, human heart muscle and Kanamycin antibiotic.

 Epimers

The compounds with the same molecular formula but differing in configuration around one carbon atom are called Epimers. Epimeric carbon is the asymmetric carbon atom other than carbon of aldehyde or Ketone group e.g . carbon number 2, 3 and 4 of glucose .

Isomers differing as a result of variations in configuration of the —OH and —H on carbon atoms 2, 3, and 4 of glucose are referred as epimers of Glucose. Biologically, the most important epimers of glucose are mannose and galactose, formed by epimerization at carbons 2 and 4, respectively.  Mannose and Galactose are not epimers of each other as they differ in configuration around 2 carbon atoms.

Figure-1 showing epimers of glucose

Similarly D- Xylulose is the C-3 epimer of D-Ribulose

Blood Group Antigens

The antigens which determine blood types belong to glycoproteins and glycolipids.  There are three types of blood-group antigens: O, A, and B. They differ only slightly in the composition of carbohydrates.

L –Fucose is a methyl pentose and is an important component of blood group antigens. (See figure).

L-Fucose is rare L sugar found of the oligosaccharide chains of N- and O-linked glycoproteins. Glycoproteins (also known as mucoproteins) are proteins containing branched or unbranched oligosaccharide chains; they occur in cell membranes and many other situations.

Figure- 2-showing Blood-group antigens.  

All humans contain enzymes which catalyze the synthesis of the O antigen.  Humans with A-type blood also contain an additional enzyme (called A-type enzyme here) which adds N-Acetyl galactosamine to the O antigen.  Humans with B-type blood contain another enzyme (called B-type enzyme here) which adds Galactose to the O antigen.  Humans with AB-type blood contain both A-type and B-type enzymes while humans with O-type blood lack both types of enzymes. N-Acetyl glucosamine and N-Acetyl galactosamine are acetylated amino sugars.

Trehalose

Trehalose is a non reducing sugar. Sugars containing free aldehyde or ketone group can reduce other reagents e.g. . They can reduce cupric ions of Fehling and Benedict’s reagents into cuprous ions :

Cupric ( blue ) + sugar ________> Cuprous ( red ) + oxidized sugar

These tests are one of the earliest tests to detect the presence of reducing sugar in urine.

Trehalose is a disaccharide containing two glucose residues linked together by alpha1-1 glycosidic linkage. Since both the functional groups are involved in the linkage and there is no free functional aldehyde or ketone group to carry out reduction, thus Trehalose is a non reducing sugar. On the same ground Sucrose is a non reducing sugar. Sucrose has no free reactive group because the anomeric carbons of both monosaccharides units are involved in the glycosidic bond. So, sucrose neither shows reducing nor mutarotation characters.

Figure- 3-showing structure of Trehalose- 2 glucose residues linked together by Alpha 1-1 glycosidic linkage

Tests to differentiate Glucose, Fructose and Mannose

Glucose and Fructose both give –

 1) Positive Molisch Test- since both are carbohydrates. Molisch test is a general test for all types of carbohydrates.(See the details below)

 2) Positive Benedict’s test, since both are reducing sugars.

 3) Osazone formation- Both sugars give similar shaped crystals. This test is used for the identification of sugars. It involves the reaction of monosaccharide with phenyl hydrazine, a crystalline compound. All reducing sugars form osazones with excess of phenyl hydrazine when kept at boiling temperature. Each sugar has a characteristic crystal form of osazones.  The reaction involved can be represented as follows-

Figure-4- Reaction showing formation of osazones

Three molecules of phenyl hydrazine are required, the reaction takes place at first two carbon atoms. The upper equation shows the general form of the osazone reaction, which affects an alpha-carbon oxidation with formation of a bis-phenylhydrazone, known as an osazone.

D-fructose and D-mannose give the same osazone as D-glucose. The difference in these sugars present on the first and second carbon atoms are masked when osazone crystals are formed. Hence these three sugars form similar needle-shaped crystals arranged like sheaves of corn or a broom.  It is seldom used for identification these days . HPLC or mass spectrometry is used for the identification of sugars present in the biological fluids.           

                                                

 Figure-5- showing formation of osazone crystals,

Figure-6- Needle shaped crystals of Glucose, Mannose and Fructose.

4) Seliwanoff test- Monosaccharides are normally stable to dilute acids, but are dehydrated by strong acids.

          D-ribose (Pentoses)when heated with concentrated HCl yields furfural (cyclic anhydride)

          D-glucose(Hexoses) under the same conditions yields 5-hydroxymethyl furfural

Practical Applications– The furfural derivatives can condense with phenolic compounds to give colored products. This forms the basis for Molisch test. This test is a sensitive test but it is nonspecifically given by all carbohydrates. Alpha nephthol is used in this test. A purple colored ring develops if carbohydrate is present.

Similar to this Seliwanoff Test is undertaken with Resorcinol, a cherry red color is produced if fructose is present. Sucrose also gives same reaction with Seliwanoff reagent.

The other tests are Anthrone test and Bial’s test etc.

Adenosine and Adenosine Mono Phosphate

The compound that consists of ribose linked by an N-glycosidic bond to N-9 of adenine is- Adenosine

Adenosine is a nucleoside. Nucleosides are derivatives of purines and pyrimidines that have a sugar linked to a ring nitrogen of a heterocycle called heterocyclic “base by N-Glycosidic linkage.

Adenosine contains

a)    Base –Adenine and

b)    sugar- Ribose, a pentose sugar.

Base and sugar are linked together by N- glycosidic linkage.

Figure- 7-Showing the structure of Adenosine

Mononucleotides are nucleosides with a phosphoryl group esterified to a hydroxyl group of the sugar. Additional phosphoryl groups linked by acid anhydride bonds to the phosphoryl group of a mononucleotide form nucleoside diphosphates and triphosphates

Figure-8- Showing the structure of Adenosine Mono Phosphate

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Q.1- Choose the odd one out

Heparin, Heparan, Dermatan, Dextran                                

(Dextran)

Q.2- Choose the odd one out

Starch, Glycogen, Chitin, Inulin                                         

(Chitin)

Q.3- Which out of the following dextrins does not give color with iodine

Achrodextrins, Erythrodextrins, Amylodextrins                            

(Achrodextrins)

Q.4- Name a non sulfated Heteropolysaccharide                

(Hyaluronic acid)

Q.5- Which heteropolysaccharide is used as an anticoagulant       

(Heparin)

Q.6- Which sugar acid is used for the detoxification of the foreign compounds?

(Glucuronic acid)

Q.7- Which monosaccharide is used as the preferred source of energy for the brain cells?

  (Glucose)

Q.8-Which monosaccharide is used as a source of energy for the spermatozoa?

(Fructose)

Q.9- Which disaccharide is an intermediate in the hydrolysis of starch?

(Maltose)

Q.10- Which monosaccharide is optically inactive?             

(Dihydroxy acetone)

 Q.11- What is odd out of the following four

Glucose, Galactose, Mannose and Fructose                        

(Fructose)

Q.12- Choose the ketopentose-

Ribose, Xylose, Xylulose and Arabinose                              

(Xylulose)

Q.13- Name a six membered sugar alcohol              

(Sorbitol, Mannitol or Galacitol)

Q.14- Name a sugar acid                                        

(Gluconic acid)

Q.15- Name an amino sugar acid                             

(Neuraminic acid)

Q.16- Name an intracellular polysaccharide              

(Heparin)

Q.17- D and L isomers differ from each other by orientation around which C atom?

(Penultimate carbon, farthest from the most oxidized C atom)

Q.18- Alpha and Beta anomers differ in orientation around 5 th carbon atom in a hexose- True or false ?                                                                 

(False)

Q.19- Malt sugar is———————— ?                      

(Maltose)

Q.20-Out of Lactase and Cellulase which enzyme is absent in human beings?

(Cellulase)

Q.21- Mucic acid is produced from—- ?                   

(Galactose)

Q.22- Give an example of Glycosylamine                           

(Ribosylamine)

Q.23- Name a sugar alcohol with five carbon atoms           

(Ribitol)

Q.24- Powder-puff shaped crystals are formed by——        

(Lactose)

Q.25- Name two non reducing sugars                               

(Sucrose and Trehalose)

Q.26- Which test is used to differentiate between aldohexose and ketohexose?                                                                              (Seliwanoff test)

Q.27- Benedict’s test is more sensitive than Fehling test. True or false?

 (True)

Q.28- Glycogen is stored mainly in muscles. True or false?   

(False)

Q.29- Name a cardiac Glycoside                              

(Digitalis)

Q.30- What is milk sugar ?                                               

(Lactose)

Q.31- Name the product of reaction of a strong acid on a pentose

(Furfural)

Q.32- What are enediols?                    

(Double bonded carbon atoms each having OH group attached)

Q.33- Name a 7 Carbon atoms containing ketose sugar     

(Sedoheptulose)

Q.34- Name the alcohol produced from the reduction of Glyceraldehyde.

(Glycerol)

Q.35- How many isomers of Glucose are found in the biological system?

(32, including anomers)

Q.36- Glucuronic acid produced from the reduction or oxidation of Glucose?

 (Oxidation)

Q.37- Dextrin or Dextran, which out of the two is used as plasma expander?

(Dextran)

Q.38- Which one is a branched polymer out of the two-

Amylose or Amylopectin?                                        

(Amylopectin)

Q.39- Reddish brown color with iodine is given by which carbohydrate?

  (Glycogen)

Q.40- Which sugar is called as Invert sugar?             

(Sucrose)

Q.41- Agar is a homo or hetero polysaccharide?                 

(Homopoysaccharide)

Q.42- Keratan or Heparan Sulfate which out of the two does not contain a sugar acid ?

(Keratan sulfate)

Q.43- Name an epimer of Sorbitol                                     

(Mannitol)

Q.44- Name an epimer of Glucuronic acid                         

(Iduronic acid)

Q.45- How are galactose and fructose related to each other?

(Isomers)

Q.46- What is Aglycon?             

(Non carbohydrate component in a glycoside)

Q.47- Maltose is composed of what kind of monosaccharides?

(Glucose – glucose)

Q.48- Name a pentose sugar present abundantly in heart muscle           

(Lyxose)

Q.49- Name a deoxy sugar                                               

(Deoxy ribose)

Q.50- Name the polysaccharide present in the exoskeleton of insects

(Chitin)

Q.51- What type of linkage is present between Galactose and Glucose in Lactose?

β (1→4) glycosidic linkage

Q.52- The compounds having same structural formula but differing in configuration around one carbon atom are called-                                  

(Epimers)

Q.53- What type of linkages are present in Glycogen?

(α(1→4) in the chain and α(1→6) at the branch point

Q.54- Name a fructosan                                         

(Inulin)

Q.55- Name a Galactosan                                       

(Agar)

Q.56- Name the test for detection of carbohydrates in a solution

(Molisch test)

Q.57- When a hexose is made to react with a strong acid, what is the product called?

  (Hydroxy methyl furfural)

Q.58- How are Mannose and Glucose related to each other?

(C-2 epimers)

Q.59- When both aldehyde and primary alcoholic groups are oxidized in mannose, what is the product called?                                       (Mannaric acid)                

Q.60- Dulcitol is produced from the reduction of which sugar?

 (Galactose)

Q.61- Name two amino sugars                               

(Glucosamine and Galactosamine)

Q.62- Out of Mucic acid and Muramic acid which one is an amino sugar acid?

(Muramic acid)

Q.63- Name a sugar ester                             

(Glucose 6 phosphate)

Q- 64- Which out of the following will give Bial’s test positive

Glucose, Fructose, ribose                              

(Ribose)

Q.65- All except one will exhibit mutarotation?

Sucrose, Maltose, Glucose, Galactose            

(Sucrose)

Q.66- Out of Pyranose and Furanose ring which one is commonly formed by Fructose ?

 (Furanose)

Q.67- Which out of the two has more carbohydrate content?

Proteoglycan or Glycoproteins                       

(Proteoglycan)

Q.68- Name the storage polysaccharides                 

(Glycogen, Starch, Inulin etc )

Q.69- Cornea is rich in which type of mucopolysaccharides?

(Keratan sulfate)

Q.70 -Name C-4 epimers                              

(Glucose and Galactose)

Q.71- Name a keto triose                             

(Dihydroxy acetone)

Q.72- Name the alcohol produced from the reduction of Fructose

(Sorbitol and Mannitol)

Q. 73- Glucose is the only source of energy for what kind of cells?

 ( Red blood cells and the cells which lack mitochondria )

Q.74- How is Aldonic acid produced from a monosaccharide        

(By the oxidation of aldehyde group of an aldose sugar)

Q.75- What type of linkages are present between glucose residues in Cellulose?

(Beta 1, 4 Glycosidic linkages)

Q.76- Out of all the biologically important mucopolysaccharides which one is the most negatively charged?                                             (Heparin)

Q.77- Which monosaccharide is present as a structural component of RNA?

 (Ribose)

Q.78- What is dextrose?                               

(D- Glucose)

Q.79- What is table sugar?                                      

(Sucrose)

Q.80- What is animal starch?                         

( Glycogen )

Q.81- What is Muta rotation ?

Carbohydrates can change spontaneously between alpha and  beta configurations through intermediate open chain formation, this leads to a process known as Mutarotation.

Q.82- Which hexose is an important component of glycoproteins?

(Mannose)

Q.83- When equal amount of dextrorotatory and levorotatory isomers are present in a mixture, the mixture is said to be —— ?                           

(Racemic )

Q.84- Glucose when treated with bromine water produces —— ?

(Gluconic acid)

Q.85- Name a glycoside which is an inhibitor of Sodium Potassium ATPase pump.

(Oubain)

Q.86- What is the storage form of glucose in plants?

(Starch)

Q.87 – Name an amino sugar acid which is present in gangliosides.

(NANA- N -acetyl Neuraminic acid)

Q.88- Deoxy ribose is synthesized from ribose by removal of oxygen around which carbon atom?                                                                      

( C-2)

Q.89- The carbohydrate of blood group substance is —– ?

(Fucose)

Q.90- Which of the following is not a polymer of Glucose?

Cellulose, Inulin. Glycogen, Dextrins                        

(Inulin)

Q.91- Which of following is an anomeric pair?

a) D-glucose and L-glucose         b) α-D-glucose and β-D-glucose            

(α-D-glucose and β-D-glucose)

Q.92- Choose the odd one out-

Muramic acid, Mucic acid. Mannaric acid, Mannonic acid     

(Muramic acid)

Q.93- The cyclical structure of Glucose is represented by-

Glucopyranose, Glucofuranose or Glucoside                      

(Glucopyranose)

Q.94- What kind of monosaccharides will be produced by lactose hydrolysis?

 (Glucose and Galactose)

Q.95- Name a keto hexose                                                         

(Fructose)

Q.96- What is an asymmetric carbon atom?

(A carbon atom with all the four different attachments is called as an asymmetric carbon atom)

Q.97- How many isomers of glyceraldehyde are possible?

 (D and L)

Q.98- How are Ribose and Ribulose related to each other?

 (Aldose, ketose isomers)

Q.99- What is the repeating disaccharide unit in Hyaluronic acid?

(D-glucuronate + GlcNAc) n

Q.100- Name an Aldotetrose which is an intermediate of HMP pathway?

 (Erythrose-4 P )

 

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Case Details

A 54 –year- old woman who was bed bound in a nursing home began to develop swelling of her left leg. She was evaluated with venous Doppler ultrasound and was found to have a deep vein thrombosis. She was immediately started on heparin to prevent the clot from further enlarging.

What is the chemical nature of Heparin?

How will it help in preventing the clot formation?

Case discussion

Heparin

Heparin also called α Heparin, is a highly sulfated GAG(Glycosaminoglycans). It is an anticoagulant widely used in clinical practice. It is present in liver, lungs, spleen and monocytes. Commercial preparations are from animal lung tissues. It contains repeating units of sulfated Glucosamine and either of the two uronic acids-D-Glucuronic acid and L-Iduronic acid. In fully formed Heparin molecules 90% or more of uronic acid residues are L-Iduronic acid. It is strongly acidic due to sulphuric acid groups and readily forms salts.

Clinical role of Heparin

In vitro Heparin is used as an anticoagulant while taking blood samples, 2 mg/10 ml of blood is used. It is considered the most satisfactory anti coagulant as it does not produce a change in red cell volume or interfere with subsequent determinations.

In vivo Heparin is used in suspected thromboembolic conditions to prevent intravascular coagulation. Heparin is used for anticoagulation for the following conditions:

  • Acute coronary syndrome,
  • Atrial fibrillation
  • Deep-vein thrombosis and pulmonary embolism.
  • Cardiopulmonary bypass for heart surgery.

Mechanism of action

Role of heparin as an anti-coagulant

It produces its major anticoagulant effect by inactivating thrombin and activated factor X (factor Xa) through an antithrombin (AT) dependent mechanism. Heparin binds to AT through a high-affinity pentasaccharide. (See figure-1)

 

Figure-1-showing the binding of heparin to antithrombin. To potentiate thrombin inhibition, heparin must simultaneously bind to antithrombin and thrombin.

 

Binding of Heparin to lysine residues in antithrombin produces conformational changes which promote the binding of the latter to serine protease “thrombin” which is inhibited, thus fibrinogen is not converted to fibrin and the coagulation is inhibited.(See figure -2)

Figure-2-showing the mechanism of action of Heparin. Heparin has a multitude of effects on the clotting cascade; however, the primary sites of action are the inhibition of factor II, also called thrombin, and factor X.
Role of Heparin as a coenzyme

Heparin acts in the body to potentiate the activity of the enzyme “Lipoprotein lipase”. Heparin binds specifically to the enzyme present in capillary walls causing its release in to the circulation. Hence it is also called “releasing factor”.

Administration of Heparin

Heparin is given parenterally, as it is degraded when taken by mouth. It can be injected intravenously or subcutaneously. Intramuscular injections are avoided because of the potential for forming hematomas.

Because of its short biologic half-life of approximately one hour, heparin must be given frequently or as a continuous infusion. However, the use of low-molecular-weight heparin (LMWH) has allowed once-daily dosing, thus not requiring a continuous infusion of the drug. If long-term anticoagulation is required, heparin is often used only to commence anticoagulation therapy until the oral anticoagulant Warfarin takes effect.

Adverse effects

The most common side effect is bleeding .The risk of bleeding increases with higher dosage.

A serious side-effect of heparin is heparin-induced thrombocytopenia (HIT). HIT is caused by an immunological reaction that makes platelets a target of immunological response, resulting in the degradation of platelets. This is what causes thrombocytopenia. This condition is usually reversed on discontinuation, and can generally be avoided with the use of synthetic heparins. There is also a benign form of thrombocytopenia associated with early heparin use, which resolves without stopping heparin.

There are two nonhemorrhagic side-effects of heparin treatment. The first is elevation of serum Aminotransferases levels, which has been reported in as many as 80% of patients receiving heparin. This abnormality is not associated with liver dysfunction, and it disappears after the drug is discontinued. The other complication is hyperkalemia, which occurs in 5 to10% of patients receiving heparin, and is the result of heparin-induced aldosterone suppression. The hyperkalemia can appear within a few days after the onset of heparin therapy.

Osteoporosis  – has also been reported with long-term Heparin therapy, since Heparin causes bone loss both by decreasing bone formation and by enhancing bone resorption.

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Q.1- What are storage polysaccharides? Give a brief description of each of them.

Answer- Glycogen, starch and Inulin are storage polysaccharides.

1) Glycogen- Glycogen is a readily mobilized storage form of glucose. It is a very large, branched polymer of glucose residues (Figure-1) that can be broken down to yield glucose molecules when energy is needed. Most of the glucose residues in glycogen are linked by α-1,4-glycosidic bonds. Branches at about every tenth residue are created by α-1,6-glycosidic bonds. It is the storage polysaccharide in animals and is sometimes called animal starch, but it is more branched than amylopectin present in starch.

Figure- 1-showing the structure of glycogen, Note the α-1,6-glycosidic linkage at the branch point

It is hydrolyzed by both α and β-amylases and by glycogen phosphorylase. The complete hydrolysis yields glucose. Glycogen on reaction with iodine gives a reddish brown color.

Glycogen is stored in muscle and liver. The concentration of glycogen is higher in the liver than in muscle (10%versus 2% by weight), but more glycogen is stored in skeletal muscle overall because of its much greater mass. Glycogen is present in the cytosol in the form of granules ranging in diameter from 10 to 40 nm. In the liver, glycogen synthesis and degradation are regulated to maintain blood-glucose levels as required to meet the needs of the organism as a whole. In contrast, in muscle,these processes are regulated to meet the energy needs of the muscle itself.

Glycogen is not as reduced as fatty acids are and consequently not as energy rich. But still animals store energy as glycogen? All excess fuel is not converted to fatty acids. Glycogen is an important fuel reserve for several reasons.

The controlled breakdown of glycogen and release of glucose increase the amount of glucose that is available between meals. Hence, glycogen serves as a buffer to maintain blood-glucose levels. Glycogen’s role in maintaining blood glucose levels is especially important because glucose is virtually the only fuel used by the brain, except during prolonged starvation. Moreover, the glucose from glycogenis readily mobilized and is therefore a good source of energy for sudden,strenuous activity. Unlike fatty acids, the released glucose can provide energy in the absence of oxygen and can thus supply energy for anaerobic activity.

2) Starch- It is a polymer of glucose, found in roots, rhizomes, seeds, stems, tubers and corms of plants, as microscopic granules having characteristic shapes and sizes. Most animals,including humans, depend on these plant starches for nourishment. The intact granules are insoluble in cold water, but grinding or swelling them in warm water causes them to burst. The released starch consists of two fractions.

About 20% is a water soluble material called Amylose. The majority of the starch is a much higher molecular weight substance, consisting of nearly a million glucose units, and called amylopectin.

(a) Amylose is a linear polymer of α-D-glucose, linked together by α 1→4 glycosidic linkages. It is soluble in water, reacts with iodine to give a blue color and the molecularweight of Amylose ranges between 50, 000 – 200, 000.

 (b) Amylopectin is a highly branched polymer,insoluble in water, reacts with iodine to give a reddish violet color. The molecular weight ranges between 70, 000 – 1 000, 000. Branches are composed of 25-30 glucose units linked by α 1→4 glycosidic linkage in the chain and by α 1→6 glycosidic linkage at the branch point.

Figure-2 Showing the structure of Amylopectin

Hydrolysis: Hydrolysis of starch with hot dilute acids or by enzymes gives dextrins of varying complexities, maltose and finally D-glucose

3) Inulin- Inulin is a polysaccharide of fructose (and hence a fructosan) found in tubers and roots of dahlias,artichokes,

and dandelions. It is readily soluble in water and is not hydrolysed by intestinal enzymes. It has a lower molecular weight than starch and colors yellow with iodine.

It is used to determine the glomerular filtration rate, Inulin is of particular use as it is not secreted or reabsorbed in any appreciable amount at the nephron allowing GFR to be calculated, rather than total renal filtration. However, due to clinical limitations, Inulin is rarely used for this purpose and creatinine values are the standard for determining an approximate GFR.

 

Q.2- What are structural polysaccharides? Give a brief account of each of them.

Answer- Cellulose and chitin are structural polysaccharides.

1) Cellulose-Cellulose is the chief constituent of plant cell walls. It is the most abundant of all carbohydrates .It is insoluble in water, gives no colour with iodine and consists of β -D-glucopyranose units linked byβ 1 →4 bonds to form long, straight chains strengthened by cross-linking hydrogen bonds. Mammals lack an enzyme that hydrolyzes the β 1→ 4 bonds, and so cannot digest cellulose. It is an important source of “bulk” in the diet, and the major component of dietary fibre. Microorganisms in the gut of ruminants and other herbivores can hydrolyze the linkage and ferment the products to short-chain fatty acids as a major energy source. There is some bacterial metabolism of cellulose in the human colon.

Figure-3- showing the structure of cellulose 

 

Figure-4- Showing the intrachain and interchain hydrogen bonding in cellulose molecule

Cellulose yields Glucose upon complete hydrolysis. Partial hydrolysis yields cellobiose.

Products obtained from Cellulose-

•         Microcrystalline cellulose : used as binder-disintegrant in tablets

•         Methylcellulose:suspending agent and bulk laxative

•         Oxidized cellulose:hemostat

•         Sodiumcarboxymethyl cellulose: laxative

•         Cellulose acetate:rayon; photographic film; plastics

•         Cellulose acetatephthalate: enteric coating

•         Nitrocellulose:explosives; collodion (pyroxylin)

2) Chitin is a structural polysaccharide in the exoskeleton of crustaceans and insects, and also in mushrooms. It consists of N-acetyl-D-Glucosamine units joined by β 1→ 4 glycosidic bonds. Chitin is the second most abundant carbohydrate polymer and is used commercially incoatings (extends the shelf life of fruits and meats).

 

Figure-5- showing the structureof chitin

Q.3 – What is the difference between dextrins and dextrans?

Answer-

Dextrins- are

•produced along with maltose andglucose by the partial hydrolysis of starch

•dextrins are often referred to aseither Amylo dextrins, erythrodextrins or achrodextrins

•used as mucilages (glues)

•also used in infant formulas(prevent the curdling of milk in baby’s stomach)

Dextrans- are

•products of the reaction of glucose and the enzyme Transglucosidase from Leuconostoc mesenteroides

•contains α (1,4), α (1,6) and α (1,3) linkages

•MW: 40,000; 70,000; 75,000

•used as plasma expanders(treatment of shock)

•also used as molecular sieves to separate proteins and other large molecules (gel filtration chromatography)

•Components of dental plaques.

 

Q.4- What are Glycosaminoglycans? Discuss the structure and functions of various Glycosaminoglycans.

Answer- The most abundant heteropolysaccharides in the body are the glycosaminoglycans (GAGs). GAGs arehighly negatively charged molecules, with extended conformation that imparts high viscosity to the solution. GAGs are located primarily on the surface ofcells or in the extracellular matrix (ECM). Along with the high viscosity ofGAGs comes low compressibility, which makes these molecules ideal for a lubricating fluid in the joints. At the same time, their rigidity provides structural integrity to cells and provides passageways between cells, allowing for cell migration.

The specific GAGs of physiological significance are hyaluronic acid, dermatan sulfate, Chondroitinsulfate, heparin, heparan sulfate, and keratan sulfate. These molecules are long unbranched polysaccharides containing a repeating disaccharide unit. [acidic sugar-amino sugar]n

Although each of these GAGs has a predominant disaccharide component, heterogeneity does exist in the sugarspresent in the make-up of any given class of GAG. The disaccharide units contain either of two modified sugars, N-acetyl galactosamine (GalNAc) orN-acetylglucosamine (GlcNAc), as amino sugars and uronic acid such as glucuronate or Iduronate as acidic sugars.

The amino sugar may also be sulfated on carbon 4 or 6 or on non acetylated nitrogen. The acidic sugarscontain carboxyl groups that are negatively charged at physiological pH, and together with the sulfate groups, give glycosaminoglycans their strongly negative nature.

Because of their large number of negative charges,these heteropolysaccharide chains tend to be extended in solution. They repel each other and are surrounded by a shell of water molecules. When brought together they “slip” past each other. This produces the slippery consistency of mucous secretions and synovial fluid. When a solution of GAG is compressed, the water is squeezed out and GAGs are forced to occupy a smaller volume. When the compression is released the GAGs  get back to their original, hydrated volume because of the repulsion of the negative charges. This property contributes to resilience of synovial fluid and vitreous humor of eye.

THE SPECIFIC GAGs OF PHYSIOLOGICAL SIGNIFICANCE ARE:

1) Hyaluronic acid – The repeating disaccharide unit is N-Acetylglucosamineand Glucuronic acid.

(D-glucuronate + GlcNAc) n

Figure-6-showing the structure of Hyaluronic acid

Occurrence:  Hyaluronic acid is found in synovial fluid, ECM of loose connective tissue, umbilical cord and vitreous humor of the eye. It serves as a lubricant and shock absorber. It is the only GAG that is not limited to animal tissue but is also found in bacteria.

Hyaluronic acid is unique among the GAGs because it does not contain any sulfate and is not found covalently attached to proteins. It forms non-covalently linked complexes with Proteoglycans in the ECM.

Hyaluronic acid polymers are very large (100 – 10,000 kDa) and can displace alarge volume of water.

2) Dermatan sulfate- The repeating disaccharide unit is N-Acetyl Galactosamineand L-Iduronic acid, with variable amount of Glucuronic acids.

(L-Iduronate + GalNAc sulfate) n

 Figure-7-showing the structure of Dermatan Sulfate

Occurrence:  It is found in skin, blood vessels and heart valves

3) Chondroitin sulfate- The repeating disaccharide unit is N-Acetyl galactosamine with sulfate on eitherC-4 or C-6 and Glucuronic acid. Based on presence of sulfate group, it may belabeled as Chondroitin-4-Sulfate or Chondroitin-6-Sulfate.

(D-glucuronate + GalNAc sulfate)n

 

Figure-8-showing the structure of Chondroitin Sulfate

Occurrence:  It is found in cartilages,tendons, ligaments, heart valves and aorta.

It is the most abundant GAG. In cartilages they bind collagen and hold fibers in a tight, strong network.

4) Heparin sulfate – The repeating disaccharide unitis

D- Glucosamine and L-Iduronic acid with variable amounts of Glucuronic acid. Most glucosamine residues are bound in Sulfamide linkages. Sulfate is also found on C-3 or C-6of Glucosamine and C-2 of uronic acid (An average of 2.5 Sulfate per disaccharide unit)

(D-glucuronate sulfate +N-sulfo-D-glucosamine) n

 

Figure-9-Showing the structure of Heparin Sulfate

Occurrence: Heparin is a component of intracellular granules of mast cells lining the arteries of the lungs, liver and skin (Contrary to other GAGs that are extra cellular compounds, it is intracellular). It servesas an anticoagulant.

5) Heparan sulfate: Heparans haveless sulfate groups than heparins. The repeating disaccharide unit is same as Heparin. Some glucosamines are acetylated

Occurrence-  It is an extracellular GAG found in basement membrane and as a ubiquitous component of cell surfaces

6) Keratan sulfate –The repeating disaccharide unitis N-Acetyl glucosamine and galactose (No uronic acid). The sulfate content isvariable and may be present on C-6 of either sugar.

(Gal + GlcNAc sulfate) n

Most heterogeneous GAGs because they contain additional monosaccharides such as L-Fucose, N-Acetyl Neuraminic acid and Mannose.

 Figure-10- showing the structure of Keratan sulfate

Occurrence:  cornea,bone, cartilage;

Keratan sulfates are often aggregated with Chondroitin sulfates.

Proteoglycans (mucoproteins) are formed of glycosaminoglycans (GAGs) covalently attached to the core proteins. They are found in all connective tissues, extracellular matrix (ECM) and on the surfaces of many cell types. Proteoglycans are remarkable for their diversity (different cores, different numbers of GAGs with various lengths and compositions).

Structure of Proteoglycans

All of the GAGs, except Hyaluronic acid are found covalently attached to protein forming proteoglycan monomers.

Structure of Proteoglycan monomer

A Proteoglycan monomer foundin cartilage consists of a core protein to which the linear GAG chains are covalently linked. These chains  which each may be composed of more than 100 monosaccharides, extend out from the core protein and remain separated from each other because of charge repulsion. The resulting structure resembles a ‘Bottle brush’(see figure). In cartilage proteoglycans,the species of glycosaminoglycans include Chondroitin sulfate and Keratan sulfate.

 

 

Figure- 11-showing the structure of Proteoglycan  monomer(Bottle Brush)

 Linkage between the carbohydrate chain and the protein

The linkage of GAGs such as (heparan sulfates andChondroitin sulfates) to the protein core involves a specific 

trisaccharide linker(Galactose-galactose-Xylose). The protein cores of Proteoglycans are rich in Ser and Threonine residues which allow multiple GAG attachments.

An O-Glycosidic bond is formed between the Xylose andthe hydroxyl group of Serine. Some forms of keratan sulfates are linked to the protein core through an

N-asparaginyl bond (N-Glycosidic linkage )

Proteoglycan Aggregates- The proteoglycan monomers associate with a molecule of Hyaluronic acid to form Proteoglycan aggregates. The association is not covalent, but occurs primarily through ionic interactions between the core protein and Hyaluronic acid. The association is stabilized by additional small proteins called Link proteins.

 

Figure-12- showing the structure of proteoglycan aggregate

Functions of Proteoglycans

They perform numerous vital functions within the body.

GAG dependent functions can be divided into two classes:the biophysical and the biochemical.

1) The biophysical functions depend  on the unique properties of GAGs: the ability to fill the space, bind and organize water molecules and repel negatively charged molecules. Because of high viscosity and low compressibility they are ideal for a lubricating fluid in the joints. On the other hand their rigidity provides structural integrityto the cells and allows the cell migration due to providing the passageways between cells.

2) The other, more biochemical functions of GAGs are mediated by specific binding of GAGs to other macromolecules,mostly proteins. Proteoglycansparticipate in cell and tissue development and physiology.

3) Heparin acts as an anticoagulant and is used in the clinical practice.

Q.5-What do you understand by the term mucopolysaccharidoses? Give a brief accountin a tabular manner.

Answer-Glycosamino glycans are degraded by Lysosomal Hydrolases. A deficiency of one of the Hydrolase results in a mucopolysaccharidoses.These are hereditary disorders in which the Glycosamino glycans accumulate in tissues, causing symptoms such as skeletal and extra cellular matrix deformities, and mental retardation.

Type

Main diseases

Deficient enzyme

Accumulated products

Symptoms

MPS I

Hurler’s syndrome

α-L-Iduronidase Heparan sulfateDermatan sulfate
  • Mental retardation
  • Micrognathia
  • Coarse facies
  • Macroglossia
  • Retinal degeneration
  • Corneal clouding
  • Cardiomyopathy

MPS II

Hunter syndrome

Iduronate sulfatase
  • Heparan sulfate
  • Dermatan sulfate
  • Mental retardation

(similar, but milder, symptoms to Hurler syndrome)

MPS III

Sanfilippo syndrome A

Heparan sulfamidase
  • Heparan sulfate
  • Developmental delay
  • Severe hyperactivity
  • Spasticity
  • Motor dysfunction
  • Death by the second decade

Sanfilippo syndrome B

N-acetylglucosaminidase

Sanfilippo syndrome C

Acetyl-CoA:alpha-glucosaminide acetyltransferase

Sanfilippo syndrome D

N-acetyl glucosamine 6-sulfatase

MPS IV

Morquio syndrome A

Galactose-6-sulfate sulfatase
  • Keratan sulfate
  • Chondroitin 6-sulfate
  • Severe skeletal dysplasia
  • Short stature
  • Motor dysfunction

Morquio syndrome B

Beta-galactosidase
  • Keratan sulfate

MPS VI

Maroteaux-Lamy syndrome

N-acetylgalactosamine-4-sulfatase
  • Dermatan sulfate
  • Severe skeletal dysplasia
  • Short stature
  • Motor dysfunction
  • Kyphosis
  • Heart defects

MPS VII

Sly syndrome

β-glucuronidase
  • Heparan sulfate
  • Dermatan sulfate
  • Chondroitin 4,6-sulfate
  • Hepatomegaly
  • Skeletal dysplasia
  • Short stature
  • Corneal clouding
  • Developmental delay

MPS IX

Natowicz syndrome

Hyaluronidase
  • Hyaluronic acid
  • Nodular soft-tissue masses around joints
  • Episodes of painful swelling of the masses
  • Short-term pain
  • Mild facial changes
  • Short stature
  • Normal joint movement
  • Normal intelligence

Laboratory Investigations

1)   Urine test,which shows the excessive excretion of undegraded mucopolysaccharides, which isspecific for a specific type.

2)   Cetyl Trimethyl ammonium bromide test is undertaken to confirm the presence of gylcosaminoglycans in urine.

3)    Absence of Lysosomal enzyme in cultured fibroblasts.

4)    Culture of cells from amniotic fluid obtained by amniocentesis for enzyme testing (prenatal testing)

5)    X-ray of spine and chest.

Prenatal diagnosis using amniocentesis and chorionic villous sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. Genetic counselling can help parents who have a family history of the Mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders.

Treatment

This disease can be treated by bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) preferably before the age of 18 months. Abnormal physical characteristics, except for those affecting the skeleton and eyes, can be improved, and neurologic degeneration can often be halted. BMT and UCBT are high-risk procedures with high rates of morbidity and mortality. There is no cure for Mucopolysaccharidoses.

Gene therapy is under  trial as a permanent cure. Enzyme replacement therapies are currently in use, they have proven useful in reducing non-neurological symptoms and pain.

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Q.1- Give a brief account of the disaccharides of biological importance.

Answer- The disaccharides are sugars composed of two monosaccharide residues linked by a glycoside bond. The glycosidic bonds are readily hydrolyzed by acids but resist cleavage by alkaline hydrolysis.The glycosidic linkage is formed by loss of one molecule of water as shown in the reaction below

The physiologically important disaccharides are as follows

1) Maltose- It is also called ‘Malt sugar’ and is composed of 2 glucose monomers in an  α-(1,4) glycosidic bond. 

Figure-1- showing the structure of Maltose

It is produced by the partial hydrolysis of starch (either salivary amylase or pancreatic amylase) and is used as a nutrient (malt extract; Hordeum vulgare); as a sweetener and as a fermentative reagent. It is hydrolyzed to glucose by maltase.

Since it has a free active group hence- it is reducing in nature, can exist in α and

βanomeric forms and can exhibit mutarotation. 

2) Lactose- is also called ‘Milk Sugar’ and is composed of galactose joined to glucose by a β-1,4-glycosidic linkage.

Figure-2- showing the structure of Lactose

Lactose is the only carbohydrate of milk (7gm% and 4gm% in human& bovine milk respectively). It is synthesized by mammary glands during lactation and is the best food for infants [Least sweet-laxative-non fermentable). It has a free active group, shows reducing properties and exhibits mutarotation.

Milk contains the α and β-anomers in a 2:3 ratio. β-lactose is sweeter and more soluble than ordinary α – lactose. It is used in infant formulations, medium for penicillin production and as a diluent in pharmaceuticals. Lactose is hydrolyzed to its component monosaccharides by lactase in human beings and by β -galactosidase in bacteria. Lack of lactase (alactasia) leads to lactose intolerance—diarrhea and flatulence; Lactose may be excreted in the urine in pregnancy

 3) Sucrose- Sucrose (common table sugar) is obtained commercially from cane or beet. The anomeric carbon atoms of a glucose unit and a fructose unit are joined in this disaccharide; the configuration of this glycosidic linkage is α-for glucose and β-for fructose. Sucrose can be cleaved into its component monosaccharides by the enzyme sucrase. Sucrase, lactase, and maltase are located on the outer surfaces of epithelial cells lining the small intestine. Rare genetic lack of sucrase leads to sucrose intolerance— diarrhoea and flatulence.

 Figure-3- showing the structure of Sucrose.

 Sucrose has no free reactive group because the anomeric carbons of both monosaccharides units are involved in the glycosidic bond. So, sucrose neither shows reducing nor mutarotation characters. Sucrose is called invert sugar because the optical activity of sucrose ( dextrorotatory) is inverted after hydrolysis [by an acid or an enzyme (invertase or sucrase)] into equimolar mixture of its two components glucose (+52.5) and fructose (-92.5) and the optical activity of the mixture becomes levorotatory.  

 4) Lactulose- is composed of β-galactose and β fructose in a β -(1,4) glycosidic bond. It is a semi-synthetic disaccharide (not naturally occurring) and is not absorbed in the GI tract. It is used either as a laxative or in the management of portal systemic encephalopathyIt is metabolized in distal ileum and colon by bacteria to lactic acid, formic acid and acetic acid. In chronic liver diseases the level of ammonia in the blood is increased, so, the oral Lactulose by microfloral conversion in the colon to organic acid will relieve the high ammonia. On the other hand, the osmotic activity of the disaccharide will cause diarrhea which will remove toxic products.

 5) Isomaltose- is composed of two glucose unite linked by α 1,6 glycosidic linkage. It is produced by enzymatic hydrolysis of starch (at the branch point in Amylopectin).

Figure-4- showing the structure of Isomaltose, 2 glucose units are linked together by α 1,6 glycosidic linkage
Q.2– Enlist the Oligosaccharides of biological importance

 Answer- Oligosaccharides are condensation products of three to ten monosaccharides. Most are not digested by human enzymes. Some of the Oligosaccharides of biological importance are as follows-

Trisaccharide: Raffinose (glucose, galactose and fructose)

Tetrasaccharide: Stachyose (2 galactose, glucose and fructose)

Pentasaccharide: Verbascose (3 galactose, glucose and fructose)

Hexasaccharide: Ajugose (4 galactose, glucose and fructose)

 

Figure-5- showing the structure of Stachyose (2 galactose, glucose and fructose).

Stachyose is a constituent of many plants and is used to prevent constipation. Melezitose- a constituent of honey also contains Glucose, fructose and some volatile oils. Cycloheptamylose- a breakdown product of starch is used in chromatographic procedures

.                        

 

 Figure –6-showing the structure of Cycloheptamylose

Oligosaccharides occur widely as components of antibiotics derived from various sources- e.g.- Bleomycin A(An antitumor agent) and Streptomycin used as broad spectrum Antibiotic are oligosaccharides.

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Q.1- What are sugar alcohols? How are they produced in the body? What is their biological or clinical significance?

 Answer- Sugar alcohols are produced by the reduction of the carbonyl group (Aldehyde/ ketone group) of monosaccharides. The reaction can be represented as follows-

a) Reduction of aldoses takes place at C-1 to form sugar alcohol

Figure-1 -showing the formation of Sugar alcohol from Aldose sugar

b) Reduction of Ketose sugars takes place at C-2 to form Sugar Alcohol

Figure-2 showing the formation of Sugar alcohol from ketose sugar

Details of Reaction-

Under specific conditions of temperature and pressure, sugars can be reduced in the presence of hydrogen. The resultant product is a polyol or sugar alcohol (alditol)

but reduction of ketose sugar produces a new asymmetric carbon atom (See figure ), thus two types of  sugar alcohols can be produced, which are epimer of each other.

Examples

1)   Glucose form Sorbitol (glucitol)

2)   Mannose forms mannitol

3)   Fructose forms a mixture of mannitol and sorbitol

4)   Galactose forms Dulcitol

5)   Glyceraldehyde gives glycerol

6)   Ribose forms Ribitol

Structure and Significance of some Sugar alcohols-

1) Sorbitol- In Diabetes Mellitus excess of Glucose is converted to Sorbitol. The osmotic effect of Sorbitol is responsible for many of the complications of diabetes mellitus e.g. Cataract formation in lens. Clinically sorbitol is dehydrated and nitrated to form Isosorbide mono and dinitrate, both of which are used for the treatment in Angina.

2) Mannitol- Mannitol is also osmotically active and is used as an infusion to lower the intracranial tension by producing forced diuresis.

3) Dulcitol- excess of galactose in galactosemia is converted to Dulcitol. The osmotic effect of Dulcitol is similar to Sorbitol and is responsible for premature cataract formation in affected patients of galactosemia.

4) Xylitol- is produced in Uronic acid pathway of Glucose utilization; it is subsequently oxidized to produce D- Xylulose.

5) Glycerol- is produced from Glyceraldehyde. Glycerol is used for the formation of Triglycerides and phospholipids. Clinically glycerol is nitrated to form Nitroglycerine , that is used for the treatment of angina.

6) Myo- Inositol- It is hexahydroxy alcohol, also considered a vitamin It is present in the plasma membrane and acts as a second messenger for the action of hormones.

7) Ribitol- is used in the formation of vitamin B2- (Riboflavin )

Figure-3- Showing the structures of commonly found sugar alcohols

Q.2- What are Glycosides? Discuss the clinical significance of Glycosides.

Answer- Acetal or ketal derivatives formed when a monosaccharide reacts with an alcohol are called glycosides. They are formed by the reaction of the hydroxyl group of anomeric carbon (hemiacetal or hemiketal)of monosaccharide with hydroxy group of second molecule with the loss of an equivalent of water.

Figure-4-showing the formation of Glycosides

The second molecule may be-

1)   Another sugar (Glycon)-  e.g. formation of disaccharides and polysaccharides.

2)   Non Carbohydrate (Aglycon)- such as Methanol, Glycerol, Sterol or Steroids etc.

In naming of glycosides, the” ose” suffix of the sugar name is replaced by “oside”, and the alcohol group name is placed first. For example, D-glucose reacts with methanol in an acid-catalyzed process: the anomeric carbon atom reacts with the hydroxyl group of methanol to form two products, methyl α -D-glucopyranoside and methyl β -D-glucopyranoside. These two gluco pyranosides differ in the configuration at the anomeric carbon atom. The new bond formed between the anomeric carbon atom of glucose and the hydroxyl oxygen atom of methanol is called a glycosidic bond specifically, an O-glycosidic bond. See figure below.

Figure- 5-Showing Methyl Glucopyranoside

The anomeric carbon atom of a sugar can be linked to the nitrogen atom of an amine to form an N-glycosidic bond. Nucleosides are adducts between sugars such as ribose and amines such as adenine (the linkage between them is N-Glycosidic linkage).

Examples of Glycosides-Glycosides are present in many drugs, spices and in the constituents of animal tissues. Glycosides comprise several important classes of compounds such as hormones, sweeteners, alkaloids, flavonoids, antibiotics, etc. The glycosidic residue can be crucial for their activity or can only improve pharmacokinetic parameters.

1) Cardiac Glycosides

Cardiac glycosides all contain steroids or genin component as aglycone in combination with sugar molecules. These include derivatives of digitalis and strophanthus such as oubain.

 2) Other glycosides such as streptomycin are used as antibioticsPhloridzin is another glycoside which is obtained from the root and bark of apple tree. It blocks the transport of sugar across the mucosal cells of small intestine and also renal tubular epithelium. It displaces Na+ from the binding site of “carrier protein” and prevents the binding of sugar molecule and produces Glycosuria.

 3) Glycosides of vitamins, both hydrophilic and lipophilic often occur in nature. Glycosylated vitamins have an advantage over the respective aglycone in their better solubility in water (especially the lipophilic ones), stability against UV-light, heat and oxidation, reduction of the bitter taste and odor(e.g., thiamine), and resistance to an enzymatic action. Some of the vitamin glyco conjugates have altered or improved Pharmacokinetic properties.

 Q.3- What are Amino Sugars and amino sugar acids? Discuss in brief about their biological importance?

 Answer- Amino groups may be substituted for hydroxyl group of sugars to give rise to amino sugars. Generally, the amino group is added to the second carbon of the hexoses. The most common aminosugars are Glucosamine and Galactosamine.

Figure- 6-Showing amino sugars.The OH group present at the second position is replaced by NH2 group

 The amino group in the sugar maybe further acetylated to produce N-Acetylated sugars such as N-AcetylGlucosamine (GluNac ) and N-Acetyl-Galactosamine(GalNAc), etc. These are important constituents of glycoproteins, mucopolysaccharides and cell membrane antigens. Glucosamine is the chief constituent of cell wall of fungi and a constituent of shells of crustaceae (Crabs, Lobsters etc), where it is found as a polymer of N-Acetyl Glucosamine called Chitin. Hence this amino sugar is also called Chitosamine.

Galactosamine occurs as N-Acetyl Galactosamine in Chondroitin sulphates which are present in cartilages, bones, tendons and heart valves. Hence Galactosamine is also called Chondrosamine.

Certain antibiotics, such as Erythromycin, Carbomycin contain amino sugars.

In some amino sugar the anomeric OH group is replaced by amino group. e.g. Ribosylamine, which is used for the de novo synthesis of Purine nucleotides.

Amino sugar acids are produced by condensation of amino sugar with Pyruvic or lactic acid. E.g.Muramic acid is produced by the condensation of lactic acid with D- Glucosamine. Certain bacterial cell walls contain Muramic acid.

N-Acetyl Neuraminic acid is formed from the condensation of Pyruvic acid with N-Acetyl Mannosamine.(Figure)

 

Figure-7- showing the structure of amino sugar acids

N-Acetyl Neuraminic acid (NANA), also called Sialic acid, is a nine carbon derivative and is an important component of glycoproteins and gangliosides (lipids). Neuraminidase is the enzyme which removes NANA from its binding with other compounds.

Q.4- What are deoxy sugars? How are they produced in the body? What is their biological significance?

Answer- Deoxy Sugars are monosaccharides which lack one or more hydroxyl groups on the molecule. They are formed by the removal of oxygen, generally from OH group present at C-2  or other locations of monosaccharides 

Examples of deoxy Sugars-
1) One quite ubiquitous deoxy sugar is2’-deoxy ribose which is the sugar found in DNA.
2) 6-deoxy-L-mannose (L-rhamnose) is used as a fermentative reagent in bacteriology.
3) L-Fucose (6-deoxy.L-galactose) is a component of glycoproteins and gangliosides of cell membranes.

Figure-8 -showing the structures of commonly found deoxy sugars.

Q.5- What is the effect of strong acids on monosaccharides?

Answer- Monosaccharides are normally stable to dilute acids, but are dehydrated by strong acids.

•  D-ribose (Pentoses) when heated with concentrated HCl yields furfural (cyclic anhydride)

• D-glucose(Hexoses) under the same conditions yields 5-hydroxymethyl furfural

Practical Applications– The furfural derivatives can condense with phenolic compounds to give colored products. This forms the basis for Molisch test. This test is a sensitive test but it is nonspecifically given by all carbohydrates. Alpha nephthol is used in this test. A purple colored ring develops if carbohydrate is present.

Similar to this Seliwanoff Test is undertaken with Resorcinol, a cherry red color is produced if fructose is present.
The other tests are Anthrone test and Bial’s test etc.

Q.6- Enlist the important reactions of monosaccharides.

Or

Describe the chemical properties of the anomeric carbon in monosaccharides.

Answer- The reactions/ properties of monosaccharides are as follows-
All the reactions are taking place at C-1  (CHO) in aldoses and C-2(C=O) in ketoses, that is why these are called functional groups.

Reactions of monosaccharides-

a) Osazone formation

b) Cyanohydrin reaction

c) Reduction

d) Oxidation

e) Action of base

f) Action of acid

g) Glycoside formation

h) Ester formation

a) Osazone formation-This test is used for the identification of sugars. It involves the reaction of monosaccharide with phenyl hydrazine, a crystalline compound. All reducing sugars form osazones with excess of phenyl hydrazine when kept at boiling temperature. Each sugar has a characteristic crystal form of osazones.  The reaction involved can be represented as follows-

Reactions involved in the formation of Osazone crystals

Three molecules of phenyl hydrazine are required, the reaction takes place at first two carbon atoms. The upper equation shows the general form of the osazone reaction, which affects an alpha-carbon oxidation with formation of a bis- phenylhydrazone, known as an osazone.

D-fructose and D-mannose give the same osazone as D-glucose. The difference in these sugars present on the first and second carbon atoms are masked when osazone crystals are formed. Hence these three sugars form similar needle shaped crystals arranged like sheaves of corn or a broom.  It is seldom used for identification these days . HPLC or mass spectrometry is used for the identification of sugars present in the biological fluids.

 

Figure-9-a) showing formation of osazone crystals,     

b) Needle shaped crystals of Glucose, Mannose and Fructose.

b) Cyanohydrin reaction- It involves the reaction of an aldose with HCN. It is used to increase the chain length of monosaccharides. It results in a Cyanohydrin formation   which is then hydrolyzed to an acid and reduced to the aldehyde. It is also known as the Kiliani -Fischer synthesis. It can prepare all monosaccharides from D-glyceraldehyde.

Figure-10- showing the chain lengthening procedure by Kiliani -Fischer synthesis

c) Reduction-Sugar alcohols are produced by the reduction of the carbonyl group (Aldehyde or ketone) of monosaccharides (Check the details in sugar alcohols).

d) Oxidation- Sugar acids are produced by the oxidation of the AldehydeC-1 (Aldonic acid) or terminal hydroxyl group at C-6 of Aldo sugar (Uronic acid) or both C-1 and C-6 (Saccharic acid). Check the details in sugar acids.

e) Action of Base- Sugars are weak acids and can form salts at high pH. A1,2-enediol salt is formed as the result. This allows the interconversion of D-mannose, D-fructose and D-glucose. The reaction is known as the Lobry de Bruyn-Alberta von Eckenstein reaction.  

Enediols obtained by the action of base are quite susceptible to oxidation when heated in the presence of an oxidizing agent. Copper sulfate is frequently used as the oxidizing agent and a red precipitate of Cu2O is obtained. Sugars which give this reaction are known as reducing sugars. Some of the frequently used solutions for detecting the presence of reducing sugars in biological fluids are as follows-
1) Fehling’s solution: KOH or NaOH andCuSO4
2) Benedict’s solution: Na2CO3 and CuSO4
3) Clinitest tablets are used to detect urinary glucose in diabetics.

f) Action of Acids and

g) Glycoside formation- Check the details above.

 h) Ester formation-The –OH groups of monosaccharides can behave as alcohols and react with acids (especially phosphoric acid) to form esters.

Figure 11- Showing sugar ester

These esters serve as intermediates in several metabolic pathways

 Figure-12- showing the summary of reactions of monosaccharides

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Q.1- Discuss in brief about the isomerism in monosaccharides.

 Answer- The sugar molecules having asymmetric carbon atoms exhibit isomerism.

Asymmetric carbon atom- It is the carbon atom that is attached to four different groups. All monosaccharides except- Dihydroxy acetone, have asymmetric carbon atoms. Based on the presence of asymmetric carbon atoms the following types of isomerism of monosaccharides are observed in the human system-

1) D and L isomerism- The designation of a sugar isomer as the D form or of its mirror image as the L form is determined by its spatial relationship to the parent compound of the carbohydrates, the three-carbon sugar glycerose (glyceraldehyde), and also called reference sugar. The L and D forms of this sugar are shown in Figure-1. The orientation of the —H and —OH groups around the carbon atom adjacent to the terminal primary alcohol carbon (carbon 5 in glucose) determines whether the sugar belongs to the D or L series. When the —OH group on this carbon is on the right (as seen in Figure-1), the sugar is the D isomer; when it is on the left, it is the L isomer.

 Figure-1 showing D and L isomers of Glyceraldehyde

Glyceraldehyde has a single asymmetric carbon and, thus, there are two stereoisomers of this sugar. D-Glyceraldehyde and L-glyceraldehyde are enantiomers, or mirror images of each other. Dihydroxyacetone lacks asymmetric carbon atom thus it has no D and L isomers.

Most of the monosaccharides occurring in mammals are D sugars, and the enzymes responsible for their metabolism are specific for this configuration. Simple monosaccharides with four, five, six, and seven carbon atoms have multiple asymmetric carbons, they exist as diastereoisomers, isomers that are not mirror images of each other. In regard to these monosaccharides, the symbols D and L designate the absolute configuration of the asymmetric carbon farthest from the aldehyde or keto group.

D-Ribose, the carbohydrate component of RNA, is a five-carbon aldose. D-Glucose, D-mannose, and D -galactose are abundant six-carbon aldoses.

Some sugars naturally occur in the L form e.g. L-Arabinose and L-Fucose are found in glycoproteins, while L- Xylulose is produced during the metabolism of Glucose in Uronic acid pathway. It is subsequently converted to its D form.

 2) Optical Isomerism- The presence of asymmetric carbon atoms also confers optical activity on the compound. When a beam of plane-polarized light is passed through a solution of an optical isomer, it rotates either to the right, dextrorotatory (+), or to the left, levorotatory (–). The direction of rotation of polarized light is independent of the stereochemistry of the sugar, so it may be designated D(–), D(+), L(–), or L(+). For example, the naturally occurring form of fructose is the D(–) isomer. In solution, glucose is dextrorotatory, and glucose solutions are sometimes known as dextrose.

Measurement of optical activity in chiral or asymmetric molecules using plane polarized light is called Polarimetry. The measurement of optical activity is done by an instrument called Polarimeter.

 3) Epimers- Isomers differing as a result of variations in configuration of the —OH and —H on carbon atoms 2, 3, and 4 of glucose are known as epimers. Biologically, the most important epimers of glucose are mannose and galactose, formed by epimerization at carbons 2 and 4, respectively.  Mannose and Galactose are not epimers of each other as they differ in configuration around 2 carbon atoms.

D- Xylulose is the C-3 epimer of D-Ribulose. See the figure-2 for the number of possible isomers of aldoses and ketoses.

 4) Pyranose and furanose ring structures: The ring structures of monosaccharides are similar to the ring structures of either pyran (a six-membered ring) or furan (a five-membered ring) . For glucose in solution, more than 99% is in the pyranose form.

 5) Anomers- The ring structure of an aldose is a hemiacetal, since it is formed by combination of an aldehyde and an alcohol group. Similarly, the ring structure of a ketose is a hemiketal.  The ring can open and reclose allowing the rotation to occur around the carbon bearing the reactive carbonyl group yielding two possible configurations- α and β  of the hemiacetal and hemiketal. The carbon about which this rotation occurs is called Anomeric carbon and the two stereoisomers are called Anomers. Crystalline glucose is α-D-glucopyranose. The cyclic structure is retained in solution, but isomerism occurs about position 1, the carbonyl or anomeric carbon atom, to give a mixture of α-D-glucopyranose (38%) and β-D glucopyranose (62%). Less than 0.3% is represented by α and β- anomers of Glucofuranose.

 6) Aldose-ketose isomerism: Fructose has the same molecular formula as glucose but differs in its structural formula, since there is a potential keto group in position 2, the anomeric carbon of fructose (Figures3), whereas there is a potential aldehyde group in position 1, the anomeric carbon of glucose.

 

 

Figure-2- showing the possible isomers of  Aldose D sugars containing 3,4,5 and 6 carbon atoms. Each of them will have the L isomer also. Thus Glucose has 8+8 =16 isomers i.e. 8 D isomers and 8 L isomers. The number of possible isomers of a sugar is derived from the formula 2n , where n represents the number of asymmetric carbon atoms. Taking in to account the α  and β  anomers , there are 32 possible isomers of Glucose.

 

Figure- 3- Showing the possible isomers of ketose sugars (D) with 3, 4 ,5 and 6  carbon atoms. The number of asymmetric carbon atoms are less in ketose sugars, thus there are less isomers as compared to aldose with the same number of carbon atoms. Dihydroxy acetone has no isomer while fructose has 3 asymmetric carbon atoms, so it has in total 8 isomers, 4 D and 4 L isomers, taking in to account the α and β anomers, there are 16 possible isomers of fructose.

 Q.2- What is Mutarotation? Describe in context to Glucose.

 Answer- Carbohydrates can change spontaneously between α and β configurations through intermediate open chain formation, this leads to a process known as Mutarotation. There is gradual change in optical rotation of the solution. This can be explained as follows-

 

 

 Figure-4- Showing mutarotation of Glucose

When D Glucose is crystallized at room temperature and a fresh solution is prepared, its specific rotation of polarized light is +112ο , but after 12-18 hours it changes to +52.5 ο

If the initial crystallization takes place at 98 ο and then solubilized, the specific rotation is found to be +19 ο, which also changes to +52.5 ο within a few hours. This change in rotation with time is called Mutarotation. At room temperature the alpha form predominates and the specific rotation is+112ο, there is transient ring opening and change in configuration. In the second condition when the crystallization takes place at 98 ο , the Beta form predominates and the specific rotation is+19 ο. Both undergo Mutarotation and at equilibrium one third molecules are α type and two third are β variety to get the specific rotation of +52.5 ο.

 

 Figure -5-showing graphical representation of Mutarotation.

 Q.3- What are sugar acids? Give examples of such acids and state their biological importance.

 Answer- Sugar acids are formed by the oxidation of –

1)  Aldehyde group(C1) to form Aldonic acid, or

2)  Primary Alcoholic group (C5) in an aldohexose to form uronic acid or

3)  Both groups to form Saccharic acid.

Details of Reactions- (Figure-6)

1)   Oxidation of Aldehyde group- Under mild conditions, in the presence of Hypobromous acid, the aldehyde group is oxidized to form Aldonic acid. Thus, Glucose is oxidized to Gluconic acid, Mannose to form Mannonic acid and Galactose to form Galactonic acid. Formation of Gluconic acid by the activity of Glucose oxidase is the basis for the Quantitative estimation of urinary and blood Glucose.(See details below )

2)   Oxidation of Primary Alcoholic acid- Under special conditions when the aldehyde group is protected, and the molecule is oxidized at the primary alcoholic group the product is a Uronic acid. Thus Glucose is oxidized to form Glucuronic acid, Galactose to form Galacturonic acid and Mannose is oxidized to Mannuronic acid. Glucuronic acid is used in the body for conjugation reactions to convert the toxic water insoluble compounds in to nontoxic water-soluble form, which can be easily excreted in urine. Glucuronic acid and its epimer Iduronic acid are used for the synthesis of heteropolysaccharides.

3)   Oxidation of both Aldehyde and Primary Alcoholic group-Under strong acidic conditions (Nitric acid and heat)  the first and the last carbons are simultaneously oxidized to form dicarboxylic acids, known as Saccharic acids. Glucose is thus oxidized to form Gluco Saccharic acid, Mannose to Mannaric acid and Galactose to Mucic Acid .The mucic acid forms insoluble crystals and is the basis for a test for identification of Galactose.

 

Figure-6- showing the formation of sugar acids.

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Q.1-Which of the following is a simple sugar or monosaccharide?

a) Galactose

b) Lactose

c) Maltose

d) Sucrose

Q.2- What is the molecular formula for Glucose?

a) CH3OH

b) C6H1206

c) C12H22O11

d) C6H12O5

Q.3- Maltose is composed of which two sugars?

a) Glucose and Glucose

b) Glucose and Galactose

c) Glucose and Fructose

d) Fructose and Galactose

Q.4- In which form is Glucose stored in animals?

a) Starch

b) Glycogen

c) Dextrins

d) Cellulose

Q.5-All are glucosans (polymers of glucose) except-

a) Glycogen

b) Inulin

c) Starch

d) Cellulose

Q.6- Choose the Aldose sugar out of the following-

a) Sucrose

b) Ribulose

c) Fructose

d) Ribose

Q.7- Choose the keto triose-

a) Glyceraldehyde

b) Erythrose

c) Dihydroxyacetone

d) Arabinose

Q.8- A pentose sugar present in the heart muscle is-

a) Xylose

b) Lyxose

c) Xylulose

d) Aldose

Q.9- α-D Glucose and β- D glucose are-

a) Epimers

b) Keto- Aldose Isomers

c) Anomers

d) Optical isomers

Q.10- All tests are negative for sucrose except-

a) Benedict

b) Seliwanoff

c) Barfoed

d) Osazone

Q.11- Glucose can have ————- isomers due to the presence of 4 asymmetric carbon atoms-

a) 4

b) 12

c) 8

d) 16

Q.12- Galactose and Glucose are-

a) Epimers

b) Isomers

c) Anomers

d)Ketose- Aldose isomers

Q.13- The compounds having same structural formula but differing in configuration around one carbon atom are called-

a) Optical isomers

b) Stereo isomers

c) Anomers

d) Epimers

Q.14- What does the following equation represent?   

 α-D Glucose +112ο+52.5ο  +19οβ- D glucose

 a) Stereo isomerism

b) Mutarotation

c) Optical isomerism

d) Epimerization

Q.15- The carbohydrate of blood group substance is-

a) Fucose

b) Xylose

c) Lyxose

d) Fructose

Q.16- Dulcitol is a –

a) Sugar acid

b) Amino sugar

c) Deoxysugars

d) Sugar alcohol

Q.17- Which of the following is a non reducing sugar-

a) Arabinose

b) Erythrose

c) Trehalose

d) Ribulose

Q.18- A Polysaccharide formed by β14 Glycosidic linkages is-

a) Starch

b) Dextrin

c) Glycogen

d) Cellulose

Q.19-Invert sugar is-

a) Starch

b) Glucose

c) Fructose

d) Hydrolytic product of Sucrose

Q.20- The Polysaccharide found in the exoskeleton of insects is-

a) Hyaluronic acid

b) Cellulose

c) Chitin

d) Chondrosamine

Q,21- Which of the following is a polymer of fructose?

a) Inulin

b)Dextrin

c) Cellulose

d) Glycogen

Q.22- A disaccharide produced on hydrolysis of starch is called-

a) Sucrose

b) Lactose

c) Maltose

d) Trehalose

Q.23-The typical cyclical structure of Glucose is α and β D-

a) Glucopyranose

b) Glucoside

c) Glucofuranose

d) Glucosamine

Q.24- Which test can be undertaken to differentiate between Glucose and Fructose?

a) Benedict

b) Molisch

c) Seliwanoff

d) Osazone

Q.25- Which of the following molecules is a carbohydrate?

a) C3 H7O2N

b) C13H26O2

c) C6H12O6

d) C20H40O2

Q.26- Which of the following monosaccharides is not an aldose?

a) Ribose

b) Fructose

c) Glucose

d) Glyceraldehyde

Q.27-Which of following is an anomeric pair?

a) D-glucose and L-glucose

b) α-D-glucose and β-D-glucose

c) D-glucose and D-fructose

d) α-D-glucose and β-L-glucose

Q.28- Which of the following monosaccharides is not a carboxylic acid?

a) Glucuronate

b) Gluconate

c) Glucose

d) Muramic acid

Q.29- From the abbreviated name of the compound Gal (β 1 →4) Glc, we know that:

a) The glucose residue is the β anomer.

b) The galactose residue is at the non reducing end.

c) C-4 of glucose is joined toC-1 of galactose by a glycosidic bond.

d) The compound is in its furanose form

Q.30- The compound that consists of ribose linked by an N-glycosidic bond to N-9 of adenine is:

a) A purine nucleotide.

b) A pyrimidine nucleotide.

c) Adenosine.

d) AMP

Key to answers

1)-a,  2)-b,  3)-a,   4)-b,   5)-b,  6)-d,  7)-c,  8)-b,  9)-c,  10)-b,  11)-d,  12)-a, 13)-d, 14)-b,  15)-a,  

16)-d,   17)-c,    18)-d,   19)-d,   20)-c,   21)-a,    22)-c,   23)-a,   24)-c,   25)-c,   26)-b,  27)-b,   28)-c,   29)-c,   30)-c

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