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.
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 antibiotics. Phloridzin 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.
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
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.