Main Menu


Chemistry of Proteins

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

The general structure of chromatin has been found to be remarkably similar in the cells of all eukaryotes. The most abundant proteins associated with eukaryotic DNA (somewhat more than half its mass) are histones, a family of basic proteins rich in the positively charged amino acids that interact with the negatively charged phosphate groups in DNA.

Which of the following amino acids acts as a component of histones and a precursor for Nitric oxide (NO)?

A. Arginine

B. Histidine

C. Lysine

D. Asparagine

E. Leucine

The correct answer is- A- Arginine.

Histones are nucleoproteins, rich in basic amino acids such as Arginine and Lysine. The net positive charge (due to basic amino acids), helps in binding of histones to negatively charged groups of DNA. Histones help in DNA packaging. The nucleosomes, the first level of DNA organization, are composed of DNA wound around a collection of histone molecules. Nucleosomes contain four types of histones: H2A, H2B, H3, and H4. H1 histones are the ones least tightly bound to chromatin (figure-1)

Role of histones

Figure-1- Role of histones in nucleosome formation

Arginine, a semi essential amino acid, is also a precursor for Nitric oxide that acts as a vasodilator and a smooth muscle relaxant. Nitric oxide is synthesized by nitric oxide synthase (NOS). The reaction catalyzed can be expressed as follows (figure-2)

Synthesis of Nitric oxide

Figure-2-Synthesis of nitric oxide, the reaction is catalyzed by Nitric oxide

As regards other options

B. Histidine- Histidine carries a net positive charge at physiological pH but it is not a predominant component of histones or a precursor for Nitric oxide.

C. Lysine- Lysine is a predominant component of histones, but it is not a precursor for nitric oxide.

D. Asparagine is an amide group containing amino acid; it is neither a component of histones nor a precursor for nitric oxide.

E. Leucine is also not a suitable option due to similar reasons.


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Q.1- The alpha helix rises per turn a distance of –

a) 0.54 nm                                                                          

b) 1.5 nm

c) 3 nm                                                                

d) 1.83 nm                          

Q.2- An antibiotic peptide out of the following-

a) Bleomycin                                                                     

b) Penicillin

c) Microcystine                                                                

d) Creatine                        

Q.3- Which protein out of the given has a length: width ratio >10?

a) Hemoglobin                                                                 

b) Myoglobin

c) Fibrinogen                                                                     

d) Albumin                         

Q.4- Which of the following amino acids is abundantly found in collagen?

a) Glycine                                                           

b) Serine

c) Alanine                                                                           

d) Tryptophan                  

Q.5- Choose the incorrect statement about peptide bond out of the following?

a) Partial double bond character                              

b) Stable

c) Trans in configuration                                               

d) Charged and polar     

Q.6- Which out of the following is a confirmatory test for Tryptophan?

a) Sakaguchi test                                                             

b) Ninhydrin test

c) Hopkin Cole test                                                         

d) Millon’s test                 

Q.7- Pulses contain incomplete protein since they lack-

a) Lysine                                                                             

b) Tryptophan

c) Phenyl alanine                                                             

d) Methionine                  

Q.8- All of the following are interactions that stabilize the tertiary structure of a protein except-

a) Vander Waal’s                                                             

b) Hydrogen

c) Peptide                                                                          

d) Ionic                                

Q.9- Which out of the following is NOT a non standard amino acid?

a) Hydroxy Proline                                                          

b) Beta Alanine

c) Ornithine                                                                       

d) Arginine         

Q.10- Choose the right set of amino acids in the structure of Glutathione-

a) Glutamine- Glycine-Cysteine

b) Cysteine-Glycine- Glutamic Acid

c) Glutamic acid- Glycine- Cysteine

d) Glutamic acid- Cysteine- Glycine                                                                         

Q.11- Which out of the following is not a conjugated protein?

a) Albumin                                                                         

b) Low density lipoprotein

c) Glycoprotein                                                                

d) Visual purple                               

Q.12- Which out of the following features is not observed at isoelectric pH of a protein?

a) Maximum solubility                                                  

b) Minimum Electrophoretic migration

c) Maximum precipitation                                           

d) Maximum Viscosity  

Q.13- Which out of the following is a set of hydrophobic amino acids?

a) Aspartic acid- Valine- Isoleucine

b) Arginine- Lysine- Methionine

c) Hydroxy proline- Histidine- Glutamine

d) Valine- Methionine- Isoleucine                                                           

Q.14- Choose the incorrect statement out of the following-

a) Only L amino acids are found in the biological system

b) Glycine is optical inactive

c) Tyrosine is a modified amino acid

d) Seleno cysteine is 21 st amino acid                                                                     

Q.15- Which out of the following amino acids is a precursor of niacin (Vitamin)?

a) Tyrosine                                                                         

b) Threonine

c) Tryptophan                                                                   

d) Phenyl alanine             

Q.16- Which of the following peptides is cyclic in nature?

a) Glutathione

b) Gramicidin-S

c) Met encephalin

d) Leuencephalin                                                                                                            

Q.17- Which out of the following amino acids is a precursor of a mediator of allergies and inflammation?

a) Histidine

b) Tyrosine

c) Phenyl Alanine

d) Tryptophan                                                                                                                  

Q.18-The most potent vasoconstrictor peptide out of the following is-

a) Vasopressin                                                                 

b) Angiotensin II

c) Bradykinin                                                                     

d) Angiotensinogen                                                                                                       

Q.19- Which of the following amino acids is detected by Sakaguchi test?

a) Tyrosine                                                                         

b) Tryptophan

c) Alpha amino acids                                                      

d) Arginine                                                                                                                         

Q.20- Which out of the following protein does not possess a quaternary structure?

a) Myoglobin                                                                    

b) Lactate dehydrogenase

c) Immunoglobulin M                                                    

d) Creatine Phospho Kinase


Key to Answers

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

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

OI is predominantly characterized by a generalized decrease in bone mass (osteopenia) and by brittle bones.The disorder is frequently associated with blue sclerae,dental abnormalities (dentinogenesis imperfecta),progressive hearing loss, and a positive family history.

Biochemical defect

Osteogenesis imperfecta (OI) is caused by mutations in the genes that code for type I procollagen (ie, COL1A1 and COL1A2).


The most common classification for OI was developed by Sillence. The following  types of Osteogenesis imperfecta have been reported:

  • Type I – Mild forms
  • Type II – Extremely severe
  • Type III – Severe
  • Type IV – Undefined

A few patients with many of the symptoms of OI were recently found not to have mutations in the genes for type I collagen. These patients have a characteristic lamellar patterning of bone, and distinctive clinical and radiological findings. They have been assigned the classifications of types V, VI, and VII OI.

  • Type V- Moderate to Severe
  • Type VI- Moderate to severe
  • Type VII- Moderate

Type V and VI differ in terms of inheritance.

The classification OI is not always prognostic because of variations in the clinical course. Some patients appear normal at birth and become progressively worse; others have multiple fractures in infancy and childhood, improve after puberty, and fracture more frequently later in life. Women are particularly prone to fracture during pregnancy and after menopause. A few women from families with mild variants of OI do not develop fractures until after menopause, and their disease may be difficult to distinguish from postmenopausal osteoporosis.


  • Autosomal dominant for Type I,III,IV and V
  • Autosomal recessive for Type VII, rarely AR for type II and III
  • Sporadic for type II
  • Inheritance of Type VI is unknown


Type I OI has a frequency of about 1 in 30,000. Type II OI has a reported incidence at birth of about 1 in 60,000, but the combined incidence of the three severe forms that are recognizable at birth (types II, III, and IV) may be much higher. Only a few patients with types V, VI, and VII have been reported.


Type I collagen fibers are found in the bones, organ capsules, fascia, cornea, sclera, tendons, meninges, and dermis. Type I collagen, which constitutes approximately 30% of the human body by weight, is the defective protein in Osteogenesis imperfecta. Qualitative defects (eg, an abnormal collagen I molecule) and quantitative defects (eg, decreased production of normal collagen I molecules) are described.

Clinical features

i) Skeletal effects

  • In type I OI, the fragility of bones may be severe enough to limit physical activity or be so mild that individuals are unaware of any disability. Radiographs of the skull in patients with mild disease may show a mottled appearance because of small islands of irregular ossification.
  •  In type II OI, bones and other connective tissues are so fragile that massive injuries can occur in utero or during delivery. Ossification of many bones is frequently incomplete. Continuously beaded or broken ribs (figure-1) and crumpled or bent long bones (accordina femora) may be present (figure-2). The long bones may be either thick or thin.

 Beaded ribs in OI

Figure-1- Beaded ribs in OI

 Bowing of long bones in OI

Figure-2- Bent long bones in OI

  • In types III and IV, multiple fractures from minor physical stress can produce severe deformities.The appearance of “popcorn-like” deposits of mineral in x-rays of the ends of long bones is an ominous sign.

In all forms of OI, bone mineral density is decreased. Surprisingly, fractures appear to heal normally.

ii) Ocular Features

The sclerae can be normal, slightly bluish, or bright blue (figure-3). The color is probably caused by a thinness of the collagen layers of the sclerae that allows the choroid layers to be seen. Blue sclerae, however, are an inherited trait in some families who do not have increased bone fragility. Blue sclera is not found in type IV, V, VI and VII.

 Blue sclera in OI

Figure-3- Blue sclera in OI

iii) Dentinogenesis

The teeth may be normal, moderately discolored, or grossly abnormal. The enamel generally appears normal, but the teeth may have a characteristic amber, yellowish brown, or translucent bluish gray color because of improper deposition or deficiency of dentin (figure-4).The deciduous teeth are usually smaller than normal, whereas permanent teeth are frequently bell-shaped and restricted at the base. In some patients, the teeth readily fracture and need to be extracted. The defect in dentin is directly attributable to the fact that normal dentin is rich in type I collagen.

 Dental defects in OI

Figure-4- Dental defects in OI

IV) Hearing Loss

Hearing loss usually begins during the second decade of life and occurs in more than 50% of individuals over age 30. The middle ear usually exhibits maldevelopment, deficient ossification, persistence of cartilage in areas that are normally ossified, and abnormal calcium deposits.

V) Other Features

Changes in other connective tissues can include thin skin that scars extensively, joint laxity with permanent dislocations and, occasionally, cardiovascular manifestations such as aortic regurgitation, mitral incompetence, and fragility of large blood vessels. For unknown reasons, some patients develop a hyper metabolic state with elevated serum thyroxin levels, hyperthermia, and excessive sweating .


  • OI is usually diagnosed on the basis of clinical criteria.
  • The presence of fractures together with blue sclerae, dentinogenesis imperfecta, or family history of the disease is usually sufficient to make the diagnosis.
  •  Other causes of pathologic fractures must be excluded, including battered child syndrome, nutritional deficiencies, malignancies, and other inherited disorders such as hypophosphatasia.
  • The absence of superficial bruises can be helpful in distinguishing OI from battered child syndrome.
  • X-rays usually reveal a decrease in bone density that can be verified by photon or x-ray absorptiometry.
  •  Bone microscopy can be helpful in the diagnosis.
  • A molecular defect in type I procollagen can be demonstrated in over two-thirds of patients by incubating skin fibroblasts with radioactive amino acids and then analyzing the proα chains by polyacrylamide gel electrophoresis.
  • After a mutation in a type I procollagen gene is identified, a simple PCR test can be used to screen family members at risk or for prenatal diagnosis.


  • Those with mild disorder may need little treatment when fractures decrease after puberty,
  • Women require special attention during pregnancy and after menopause, when fractures again increase.
  • More severely affected children require a comprehensive program of physical therapy, surgical management of fractures and skeletal deformities, and vocational education
  • Moderately to severely affected patients should be evaluated periodically to anticipate possible neurologic problems.
  • Counseling and emotional support are important for patients and their parents.
Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Collagen degradation though a complex process, caries an equal importance in collagen metabolism.

In normal healthy tissues where the collagen is fully hydroxylated and in a triple helical structure, the molecule is resistant to attack by most proteases. Under these normal healthy conditions, only specialized enzymes called collagenases can attack the collagen molecule.


The group of collagenases belong to a family of enzymes called matrix metalloproteinases or MMPs.

Many cells in our body can synthesize and release collagenase including fibroblasts, macrophages, neutrophils, osteoclasts, and tumor cells. One of the reasons that some cancer cells can be so invasive is because they release potent collagenases that can break down the collagen around them.They can also break down the basement membranes of blood vessels and spread throughout the body. In chronic pressure ulcers, there is a massive invasion of neutrophils, and they release a very potent collagenase called MMP-8 that is responsible for connective tissue breakdown.

Physiological turn over

During growth and development, the collagen fibrils in all tissues undergo repeated synthesis, degradation, and resynthesis. In adults, collagen fibers in most tissues undergo very little metabolic turnover. One exception is bone where collagen fibrils are degraded and resynthesized as part of lifelong remodeling.

Increased collagen degradation occurs with advancing age and also in sun exposed areas. Loss of elasticity and strength results in sagging skin and wrinkles. However, collagen maintains its structural integrity for longer if it is protected from environmental threats like UV exposure.

Variations in collagen turn over

A) The rate of collagen degradation increases under some circumstances

I)  In starvation, a large fraction of the collagen in skin and other connective tissues is degraded, thus providing amino acids for gluconeogenesis .

2)  Large losses of collagen also occur in most connective tissues during immobilization or prolonged periods of low-gravitational stress.

3) In rheumatoid arthritis, a rapid degradation of collagen occurs in the articular cartilage.

4) In cancer and chronic nonhealing ulcers, the extent of collagen degradation can be quite extensive

B) Deceased collagen synthesis

Glucocorticoids decrease the collagen content of most connective tissues, including bone, by decreasing the rate of collagen synthesis. Decreases in collagen weaken tissues.

C) Excess collagen deposition

In many pathologic states, however, collagen is deposited in excess.

1) Post inflammation- With injury to tissue, inflammation is usually followed by increased deposition of collagen fibrils in the form of fibrotic tissue and scars.

2) Post repair- The deposition of collagen fibrils during the repair process is largely irreversible and is a major feature of the pathological changes in hepatic cirrhosis, pulmonary fibrosis, atherosclerosis, and nephrosclerosis.

Disorders associated with collagen synthesis

A number of genetic diseases result from abnormalities in the synthesis of collagen. Some diseases are due to mutations in collagen genes or in genes encoding some of the enzymes involved in these posttranslational modifications (Table).

Table – Diseases caused by mutations in collagen genes or by deficiencies in the activities of enzymes involved in the posttranslational  modification of collagen

Gene or Enzyme Disease
COL1A1, COL1A2 Osteogenesis imperfecta, type 1
Ehlers-Danlos syndrome type VII autosomal dominant
COL2A1 Severe chondrodysplasias
COL3A1 Ehlers-Danlos syndrome type IV
COL4A3–COL4A6 Alport syndrome
COL7A1 Epidermolysis bullosa, dystrophic
COL10A1 Schmid metaphysial chondrodysplasia
Lysyl hydroxylase Ehlers-Danlos syndrome type VI
Procollagen N-proteinase Ehlers-Danlos syndrome type VII autosomal recessive
Lysyl hydroxylase(Secondary to deficiency of copper) Menke’s disease

Further details in the next post…. 

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

A 2-year- old child has been brought to the pediatrician because of suspected child abuse. Physical examination reveals blue sclerae, diminished hearing in both ears and radiographs of the child’s extremities show recent and healing long bone fractures. The child is diagnosed with ‘Osteogenesis imperfecta’. This disorder is a defect in the synthesis of which of the following proteins ?

a) Elastin

b) Hemoglobin

c) Collagen

d) Spectrin

e) β Myosin heavy chain

Case discussion

The right answer is – c) Collagen.

Osteogenesis imperfecta (OI) is predominantly characterized by a generalized decrease in bone mass (osteopenia) and by brittle bones. The disorder is frequently associated with blue sclerae, dental abnormalities (dentinogenesis imperfecta), progressive hearing loss, and a positive family history.

Biochemical defect

The disorder is caused by mutations in the genes that code  for type I procollagen (ie, COL1A1 and COL1A2).

General discussion of collagen


Collagen is the most abundant protein of the human body accounting to around  25-30% of the total protein content. It is the major component of most connective tissues. It is also the main fibrous component of skin, bone, tendon, cartilage, and teeth. Collagen is a Greek word which means “Glue”, it is so named since it holds the cells together in the tissues.

Types of collagen

Twenty-eight different collagens made up of over 30 distinct polypeptide chains (each encoded by a separate gene) have been identified in human tissues. Many are minor constituents that probably have highly specialized functions. They may play important roles in determining the physical properties of specific tissues.

 In addition, a number of proteins (eg, the C1q component of the complement system, pulmonary surfactant proteins SP-A and SP-D) that are not classified as collagens have collagen-like domains in their structures; these proteins are sometimes referred to as “noncollagen collagens.”

The major types are as follows-

1) Type I collagen is found throughout the body except in cartilaginous tissues. It is found in skin, tendon, vascular, ligature, organs and is the main component of bone. It is also synthesized in response to injury and in the fibrous nodules in fibrous diseases. Over 90% of the collagen in the body is type I.It is synthesized from the genes COL1A1, COL1A2. The mutations of these genes are responsible for ‘Osteogenesis Imperfecta“.

2) Type II collagen is the main component of cartilage. It is also found in developing cornea and vitreous humor. These are formed from two or more collagens or co-polymers rather than a single type of collagen.It is synthesized from the genes COL2A1.

3) Type III collagen is found in the extensible connective tissues such as skin, lung, and the vascular system such as walls of arteries and other hollow organs and usually occurs in the same fibril with type I collagen. The gene responsible for this is COL3A1.

4) Type IV collagen forms the bases of cell basement membrane. The genes  for this type are COL4A1–COL4A6

5) Type V collagen  is a minor components of tissue and occurs as fibrils with type I and type II collagen respectively. Type V forms cell surfaces, hair and placenta. It is synthesized from  COL5A1–COL5A3.

6) Type VI Collagen is present in most connective tissues and is derived from the genes COL6A1–COL6A3.

Structure of collagen

All collagen types have a triple helical structure. In some collagens, the entire molecule is triple helical, whereas in others the triple helix may involve only a fraction of the structure.

Mature collagen type I, containing approximately 1000 amino acids, belongs to the former type; in it, each polypeptide subunit or alpha chain is twisted into a left-handed helix of three residues per turn. Three of these alpha chains are then wound into a right-handed superhelix, forming a rod-like molecule 1.4 nm in diameter and about 300 nm long (Figure-1).

 triple helical structure of collagen

Figure-1- Each individual polypeptide chain is twisted into a left-handed helix of three residues (Gly-X-Y) per turn, and all of these chains are then wound into a right-handed superhelix.

Amino acid composition of collagen

A striking characteristic of collagen is the occurrence of glycine residues at every third position of the triple helical portion of the alpha chain. This is necessary because glycine is the only amino acid small enough to be accommodated in the limited space available down the central core of the triple helix. This repeating structure, represented as (Gly-X-Y)n, is an absolute requirement for the formation of the triple helix. While X and Y can be any other amino acids, about 100 of the X positions are proline and about 100 of the Y positions are hydroxy proline. Proline and hydroxy proline confer rigidity on the collagen molecule.

Hydroxylation of Proline and Lysine

Hydroxy proline is formed by the posttranslational hydroxylation of peptide-bound proline residues catalyzed by the enzyme prolyl hydroxylase, whose cofactors are ascorbic acid (vitamin C) and α-ketoglutarate. Vitamin C deficiency causes impaired hydroxylation , and defective collagen synthesis and hence is responsible for the disease scurvy. The hydroxylation is site specific, hence proline is hydroxylated to 4-hydroxy proline or 3-hydroxy proline depending upon its location relative to glycine.

Lysines in the Y position may also be posttranslationally modified to hydroxylysine through the action of lysyl hydroxylase, an enzyme with similar cofactors. Lysine is hydroxylated at position -5. The hydroxylated amino acids are of special functional significance.

Glycosylation of amino acyl residues in collagen

Some of these hydroxylysines may be further modified by the addition of galactose or galactosyl-glucose through an O-glycosidic linkage, a glycosylation site that is unique to collagen. The galactose and glucose residues are added sequentially by galactosyl and glucosyl transferases. The extent of glycosylation is different in different tissues (Figure-2).

 glycosylation of collagen

Figure-2- Glycosylation of lysine residue in collagen.

 Synthesis of collagen- To be continued in next post


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

A 2-year- old child has been brought to the pediatrician because of suspected child abuse. Physical examination reveals blue sclerae, diminished hearing in both ears and radiographs of the child’s extremities show recent and healing long bone fractures. The child is diagnosed with ‘Osteogenesis imperfecta’. This disorder is a defect in the synthesis of which of the following proteins ?

a) Elastin

b) Hemoglobin

c) Collagen

d) Spectrin

e) β Myosin heavy chain


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

A 56-year-old man with long-standing poorly controlled diabetes mellitus visits his primary care physician for a follow-up after recent hospitalization. The patient experienced an episode of acute renal failure while in the hospital and his creatinine level rose to 4 mg/dl. Creatinine, a marker of renal function is produced from which of the following precursors?

a) Glutamine, Aspartic acid and alanine

b) Glutamine, Cysteine and Glycine

c) Serine, Glycine and Methionine

d) Glycine, Arginine and Methionine

e) Glutamic acid, Cysteine and Glycine

Creatinine is an anhydrous product of creatine. Creatine, methyl guanidoacetic acid, is a tripeptide produced from Glycine, Arginine and Methionine in the human body primarily in the kidney and liver. It is transported in the blood for use by muscles. Approximately 95% of the total creatine is located in skeletal muscle. It is also present in liver, testes and brain. It can occur in free form or phosphorylated form. The phosphorylated form is called ‘Creatine-Phosphate’, ‘Phosphocreatine’ or ‘phosphagen’.

Creatine is excreted in the form of Creatinine, which is formed by removal of one molecule of water from creatine.

Creatine————–> Creatinine + H20

The reaction is non enzymatic and irreversible. About 2 % of the total Creatine is converted daily to creatinine so that the amount of creatinine produced is related to the total muscle mass and remains approximately the same in plasma and urine from day to day unless the muscle mass changes. Normal excretion ranges between 1-2 g/day.

Estimation of serum and urinary creatinine is undertaken to assess the renal functions.

The normal serum creatinine ranges as follows-

1) < 12 Years-0.25-0.85 mg/dL

2) Adult male- 0.7-1.5 mg/dL

3) Adult Female- 0.4 -1.2 mg/dL

It is higher in males because of the muscle mass.

General discussion of peptides

Peptides are short polymers of amino acids. Physiologically they perform prominent roles  in the neuroendocrine system as hormones, hormone-releasing factors, neuromodulators, or neurotransmitters. Clinically some of the peptides are used as antibiotics, anticancer drugs and some in toxic dosage promote tumor formation.

Summary of biologically important peptides (Alphabetically)

S. No. Name of Peptide Number of amino acids Physiological/ Clinical Significance
1) Angiotensins

a) Angiotensin I

b) Angiotensin II

c) Angiotensin III





Angiotensins are produced from Angiotensinogen . Renin, an enzyme produced in the juxtaglomerular cells of the renal afferent arteriole acts upon the substrate angiotensinogen to produce the decapeptide angiotensin

I.Angiotensin-converting enzyme, a glycoprotein found in lung, endothelial cells, and plasma, removes two carboxyl terminal amino acids from the decapeptide angiotensin I to form angiotensin II. Angiotensin II is the most potent vasoconstrictor of the body, it  also stimulates release of Aldosterone.Angiotensin II is converted to the heptapeptide angiotensin III, an equally potent stimulator of aldosterone production. In humans, the plasma level of angiotensin II is four times greater than that of angiotensin III, so most effects are exerted by the octapeptide.

2) Aspartame 2 Used as artificial sweetener
3) Bradykinin 9 It is a natural smooth muscle relaxant
4) Bacitracin Cyclic polypeptide Bacitracin is commercially manufactured by growing the bacteria Bacillus subtilis. It is used as a topical antibiotic .
5) β- Corticotropin (ACTH) 39 ACTH stimulates secretion of Glucocorticoid hormone from adrenal cortex cells, especially in the zona fasciculata of the adrenal glands.
6) β- MSH 18 Melanocyte-stimulating hormone (MSH) belongs to a group called the melanocortins. This group includes ACTH, alpha-melanocyte-stimulating hormone (α-MSH), beta-melanocyte-stimulating hormone (β-MSH) and gamma-melanocyte-stimulating hormone (γ-MSH); these peptides are all cleavage products of a large precursor peptide called pro-opiomelanocortin (POMC).They stimulate the production and release of melanin (melanogenesis) by melanocytes in skin and hair.
7) Bleomycin Polypeptide It is produced by the bacterium Streptomyces verticillus. Acts as an anticancer drug used in the treatment of Hodgkin’s lymphoma, testicular tumors and squamous cell carcinoma.
8) Creatine/Creatinine 3 Energy bank, stored as creatine-P in skeletal muscles, a high energy compound.
9) Carnosine 2 It is highly concentrated in muscle and brain tissues. Anserine is methylated Carnosine.
10) Dynorphin 13 Dynorphin , endogenous opioid peptide has been shown to be a modulator of pain response. Also called super opiate since it is highly potent.
11) Endorphins 5-40 Endorphins (“endogenous morphine”) are endogenous opioid peptides that are not considered to be neurotransmitter molecules, but are instead classified as neuromodulatory, that is, they modify the action of neurotransmitters through a number of effects associated with pain or pleasure.The term endorphin consists of two parts: endo- and -orphin; these are short forms of the words endogenous and morphine, intended to mean “a morphine-like substance originating from within the body. They resemble the opiates in their abilities to produce analgesia and mood elevation.
12) Gastrin Gastrin is found primarily in three forms:a) gastrin-34 (“big gastrin”)b) gastrin-17 (“little gastrin”)c) gastrin-14 (“minigastrin”)d) Also, pentagastrin is an artificially synthesized, containing  five amino acids. The presence of gastrin stimulates parietal cells of the stomach to secrete hydrochloric acid (HCl)/gastric acid.
13) Glutathione 3 Glutathione is commonly abbreviated as GSH (because of the sulfhydryl group of its cysteine, which is the business part of the molecule).It participates in the decomposition of potentially toxic hydrogen peroxide in the reaction catalyzed by glutathione peroxidase.It is an important intracellular reductant, helping to maintain essential SH groups of enzymes in their reduced state. Also helps in the transport of certain amino acids across membranes in the kidney.
14) Gramicidin S 10 (Cyclodecapeptide) Gramicidin S is an antibiotic effective against some Gram positive and Gram negative bacteria as well as some fungi.
15) Glucagon 29 (Polypeptide) Regulated blood glucose level by causing glycogenolysis and gluconeogenesis. Also causes lipolysis and reduces protein synthesis.
16) Kallidin 10 Kallidin is a bioactive kinin formed in response to injury from kininogen precursors through the action of kallikreins.Kallidin is a decapeptide that can be converted to bradykinin by the aminopeptidase enzyme. Kallidin is identical to bradykinin with an additional lysine residue added at the N-terminal end.
17) Leuenkephalin 5 Produces opioid effects, such as analgesia and mood elevation.
18) Met enkephalin 5 [Met]enkephalin, sometimes referred to as opioid growth factor (OGF), is a naturally occurring, endogenous opioid peptide that has opioid effects of a relatively short duration. [Met]enkephalin produces its opioid effects, such as analgesia and mood lift through binding to specific receptors.
19) Microcystin Cyclic peptide Hepatotoxic
20) Nodularin 5 Nodularin-R is a potent hepatotoxin and may cause serious damage to the liver.
21) Oxytocin 9 It plays a role in milk ejection from the lactating mammary glands(‘Let down reflex’)  and also promotes  uterine contractions, important for cervical dilatation during the second and third stage of labor.
22) Penicillin 3 Penicillin is a group of antibiotics derived from Penicillium fungi. The term “penicillin” is often used generically to refer to benzylpenicillin (penicillin G), procaine benzylpenicillin (procaine penicillin), benzathine benzylpenicillin (benzathine penicillin), and phenoxymethylpenicillin (penicillin V).
23) Polymyxins These are cyclic, positively charged peptides Polymyxins are antibiotics; they are used in the treatment of Gram-negative bacterial infections. Polymyxin antibiotics are relatively neurotoxic and nephrotoxic and are usually used only as a last resort if modern antibiotics are ineffective or are contraindicated.
24) Secretin 27(Polypeptide) Secretin stimulates the release of watery bicarbonate rich fluid  from pancreatic and bile duct epithelium.
25) Vasopressin 9 Arginine vasopressin (AVP), also known as vasopressin, argipressin or antidiuretic hormone (ADH), is a peptide hormone that controls the reabsorption of water in the tubules of the kidney by affecting  the cellular permeability. It also increases peripheral vascular resistance, which in turn increases arterial blood pressure. It plays a key role in the maintenance of water and electrolyte balance of the body.


Functional classification of biologically important peptides (Easy to remember)

1) Peptide hormones

i) β- Corticotropin (ACTH)

ii) β- MSH

iii) Gastrin

iv) Glucagon

v) Secretin

vi) Oxytocin

vii) Vasopressin

2) Antibiotics

i) Bacitracins

ii) Penicillin

iii) Polymyxins

iv) Gramicidin S

v) Chloramphenicol

3) Anticancer drug


4) Muscle relaxants

i) Kallidin

ii) Bradykinin

5) Vasoconstrictors

i) Angiotensins

a) Angiotensin I

b) Angiotensin II

c) Angiotensin III

ii) Vasopressin

6) Neuromodulators

i) Endorphins

ii) Enkephalin

7) Toxic peptides

i) Microcystin

ii) Nodularin

8) Biological reductant


9) Artificial sweetener


10) Muscle peptides

i) Creatine

ii) Carnosine

iii) Anserine


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Case details

A severe form of obstructive lung disease starting with dyspnea and leading progressively towards emphysema was found in several members of the family. One brother had died earlier of lung disease.

Blood plasma from his surviving brother and sister showed abnormally low concentration of α1-Antitrypsin (5.5 μm, normal is 20–48 μm), the α1-plasma fraction also moved abnormally on isoelectric focusing gel electrophoresis.

What is the relationship of emphysema with α1-Antitrypsin?

What is the cause of abnormal movement during electrophoresis?

What are the prospects for treatment of this emphysema?

Case discussion

Emphysema is a lung disease characterized by destruction of the alveolar walls. Its causes are complex but airway infection, cigarette smoking, air pollution and familial factors are involved. A deficiency in plasma α1- Antitrypsin leads to the development of emphysema and less frequently hepatic disease.


It was so named because it is a good inhibitor in vitro of pancreatic protease trypsin. It is synthesized primarily in the liver and is secreted in to the blood stream. The inhibitor makes-up most of the proteins in the α1-globulin band following the electrophoresis of plasma.

Pathogenesis of α1-Antitrypsin Deficiency

In healthy individuals, the lungs contain a natural enzyme called neutrophil elastase that, under normal circumstances, helps the lungs by digesting damaged, aging cells and bacteria. This process promotes healing of the lung tissue. Unfortunately this enzyme is nonspecific in nature and eventually attacks the lung tissue instead of helping it heal. That is where alpha antitrypsin (AAT) comes into action, by destroying the enzyme before it can cause actual damage to healthy lung tissue. It promotes the lungs to function normally. When there is not enough AAT, however, the lung tissue will continue to be destroyed, which may lead to the chronic lung disease, emphysema.


The two patients described in this case are male and female, suggesting that the deficiency is inherited as an autosomal trait. The genetics has been studied in large number of patients and family members. Analysis suggests that two independent alleles exist on chromosome 14. The deficiency is inherited as a codominant trait; that is, both alleles contribute to the disease and neither is dominant over the other. The two genes that each person carries for α1-Antitrypsin may be diverse, more than 100 variants are known.

The two common deficiency variants of a1-antitrypsin, S and Z, result from point mutations in the α1- antitrypsin gene and are named on the basis of their slower electrophoretic mobility on isoelectric focusing analysis compared with the normal M allele. S α1-antitrypsin (264Glu→Val) is found in up to 28 percent of Southern Europeans and, although it results in plasma α1-antitrypsin levels that are 60 percent of the M allele, it is not associated with any pulmonary sequelae. This is usually sufficient to protect the lungs from the effects of elastase in people who do not smoke.

The Z variant (342Glu→Lys) results in a more severe deficiency that is characterized, in the homozygote, by plasma α1-antitrypsin less than 15 percent of normal, and patients are likely to develop panacinar emphysema at a young age; 50 percent of these patients will develop liver cirrhosis, because the A1AT is not secreted properly and instead accumulates in the liver.

Clinical Manifestations

The first signs and symptoms of lung disease caused by alpha-1 antitrypsin deficiency usually appear between ages 20 and 50. The earliest symptoms are:

• Shortness of breath following mild activity,

• Reduced ability to exercise, and

• Wheezing.

Other signs and symptoms can include:

• Unintentional weight loss,

• Recurring respiratory infections,

• Fatigue,

• Rapid heartbeat upon standing.

Advanced lung disease leads to emphysema, in which small air sacs in the lungs (alveoli) are damaged.


Figure 1: Hyperinflation due to panacinar emphysema. Posteroanterior chest radiograph shows that the dome of the right hemidiaphragm is below the level of the anterior right 7th rib consistent with increased lung volumes. Also noted is decrease in the peripheral vascular markings. The patient had severe panacinar emphysema due to alpha-1 antitrypsin deficiency.

Characteristic features of emphysema include:

• Difficulty breathing,

• A hacking cough, and

• A barrel-shaped chest.

Smoking or exposure to tobacco smoke accelerates the appearance of symptoms and damage to the lungs.

About 10 percent of infants and 15 percent of adults with alpha-1 antitrypsin deficiency have liver damage.

Signs of liver disease can include:

• Ascites,

• Edema feet or legs, and

• Jaundice.


The following tests may also help with diagnosis:

• Alpha-1 antitrypsin estimation

• Arterial blood gases

• Chest X-ray (Figure 1)

• CT scan of the chest

• Genetic testing

• Pulmonary function tests.

Measurement of alpha-1 antitrypsin: Isoelectric focusing on polyacrylamide gel is useful in distinguishing specific variants to establish the specific phenotype.

Effect of smoking on antitrypsin levels: Smoking greatly exacerbates antitrypsin deficiency. A methionyl-seryl group   (position 358 and 359) is present at the point where the inhibitor binds to the active site of elastase. The smoke promotes the oxidation of Methionine residues to the corresponding sulfoxide. This results in inactivation of the protein which fails to bind elastase . The active elastase then destroys the lung tissue.


Treatment involves replacing the missing AAT protein. The protein derived from donated human plasma is given intravenously each week. This augmentation therapy is thought to arrest the course of the disease and halt any further damage to the lungs. Long-term studies of the effectiveness of A1AT replacement therapy are not available. It is currently recommended that patients begin augmentation therapy only after the onset of emphysema symptoms.

Quitting smoking is crucial.

Other treatments specifically for emphysema and cirrhosis are also used.

Treatments currently being studied include recombinant and inhaled forms of A1AT. Antioxidants are also supplemented.

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Plasma proteins

View more PowerPoint from namarta28
Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Chemistry of amino acids

View more PowerPoint from namarta28
Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Chemistry of amino acids

View more PowerPoint from namarta28
Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Group Protein Function Clinical Significance
Albumins a) Albumin 






b) Transthyretin

a)Maintenance of osmotic pressure;  transport of fatty acids, bilirubin, bile acids, steroid hormones, pharmaceutical drugs, inorganic ions; buffering and nutritive. 



b)Transport of thyroxin, triiodothyronin and retinol


a)HypoalbuminemiaLiver cirrhosis, protein energy malnutrition, mal absorption, nephrotic syndrome, protein losing enteropathy, extensive skin burns, genetic disease- Analbuminemia, Hemodilution


b) Concentration decreased in all conditions of hypoproteinemia and during infections (Negative acute phase protein)

α1-Globulins a) Antitrypsin 




b)  Antichymotrypsin



c) Lipoprotein (HDL)


d) Prothrombin


e) Transcortin



f) Acid glycoprotein




g) Thyroxin-binding globulin







a) Inhibition of Trypsin and other proteases 




b) Inhibition of Chymotrypsin


c) Transport of  cholesterol from tissues to liver


d) factor II, thrombin precursor


e) Transport of cortisol, corticosterone and progesterone


f) Transport of progesterone




g) Transport of iodothyronins





h) Present in fetal blood


a) Acute phase protein (concentration rises  during infections), deficiency associated with Emphysema and liver cirrhosis and acts as a tumour marker- increased level in germ cell tumours of testes and ovaries. 



c) Cardio protective



e) Concentration increases during pregnancy.


f)Acute phase protein




g) Level – Low in Nephrotic syndrome,

High –during pregnancy



h) Tumor marker- High concentration in Hepatocellular malignancies

α 2-Globulins a) Ceruloplasminb) Antithrombin III


c) Haptoglobin


d) Cholinesterase


e) Plasminogen




f) Macroglobulin



g) Retinol-binding protein



h) Vitamin D-binding protein

a)Transport of copper ions, ferroxidase and Histaminase activitiesb) Inhibition of blood clotting 

c) Binding of hemoglobin


d) Cleavage of choline esters


e) Precursor of plasmin breakdown

of blood clots



f) Binding of proteases, transport of zinc ions


g) Transport of vitamin A




h) Transport of Calcitriol


a) Acute phase protein, Low levels in Wilson disease and Menke’s disease. 

c) Acute phase protein,Low level in Haemolytic diseases.





f) Low level in Nephrotic syndrome


g) Level of retinol binding protein indicates vitamin A status.


h) Low level in Nephrotic syndrome and PEM


 β-Globulins a) Lipoprotein (LDL)b)Transferrin




c) Haemopexin


d)Sex hormone binding



e) Transcobalamine



f) C-reactive protein 

a) Transport of lipidsb) Transport of iron ions





c) Binds fee haem


d) Transport of testosterone and estradiol



e) Transport of vitamin B12



f) Complement activation

a) Atherogenic (Bad cholesterol)

b) Negative acute phase protein, low-level in all conditions of hypoproteinemia

High levels in iron deficiency anemia

c)Decreased level in Hemolytic disorders







f)Acute phase protein

Gamma-Globulins a) IgG 







b) IgA





c) IgM




d) IgD





e) IgE


a) Main antibody in the secondary response, Opsonizes bacteria, making them easier to phagocytose. Fixes complement, which enhances bacterial killing. Neutralizes bacterial toxins and viruses. Crosses the placenta. 




b) Mucosa-protecting antibodies

Secretory IgA prevents attachment of bacteria and viruses to mucous membranes. Does not fix complement.



c) Produced in the primary response to an antigen. Fixes complement. Does not cross the placenta. Antigen receptor on the surface of B cells.


d) B-lymphocyte receptors





e) Mediate immediate hypersensitivity by causing release of mediators from mast cells and basophils upon exposure to antigen (allergen).

Defend against worm infections by causing release of enzymes from eosinophils.

Does not fix complement.

Main host defense against helminthic infections.

High concentration in  chronic infections, chronic liver diseases, Sarcoidosis, Autoimmune diseases, Multiple myeloma and lymphoreticular malignanciesLow concentration in immunodeficiency disorders.









c) High concentration  of Ig M -in Waldenstrom’s Macroglobulenemia








e) High concentration in allergic disorders and helminthic infections.


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Immunoglobulin (Ig) 

Immunoglobulins are glycoprotein molecules that function as antibodies and are produced by plasma cells in response to an immunogen. The immunoglobulins derive their name from the finding that they migrate in the region of globulins when antibody-containing serum is placed in an electrical field.

Figure- 1-showing the  Electrophoretic separation of plasma proteins 


Although different immunoglobulins differ structurally but they all are built from the same basic units.(Figure-2)

A. Heavy and Light Chains 

All immunoglobulins have a four chain structure as their basic unit. They are composed of two identical light chains (23kD) and two identical heavy chains (50-70kD)

B. Disulfide bonds

1. Inter-chain disulfide bonds – The heavy and light chains and the two heavy chains are held together by inter-chain disulfide bonds and by non-covalent interactions .The number of inter-chain disulfide bonds varies among different immunoglobulin molecules.

2. Intra-chain disulfide binds – Within each of the polypeptide chains there are also intra-chain disulfide bonds.

C. Variable (V) and Constant (C) Regions 

Both the heavy and light chain can be divided into two regions based on variability in the amino acid sequences. These are the

1. Light Chain – VL (110 amino acids) and CL (110 amino acids)

2. Heavy Chain – VH (110 amino acids) and CH (330-440 amino acids)

D. Hinge Region 

This is the region at which the arms of the antibody molecule form a Y. It is called the hinge region because there is some flexibility in the molecule at this point.

E. Domains 

Three dimensional images of the immunoglobulin molecule show that it is not a straight molecule rather, it is folded into globular regions each of which contains an intra-chain disulfide bond (figure-2). These regions are called domains.

1. Light Chain Domains – VL and CL

2. Heavy Chain Domains – VH, CH1,CH2CH3 (or CH4)

F. Oligosaccharides 

Carbohydrates are attached to the CH2 domain in most immunoglobulins. However, in some cases carbohydrates may also be attached at other locations.

Figure-2- showing the general structure of Immunoglobulin


A. Antigen binding 

Immunoglobulins bind specifically to one or a few closely related antigens. Each immunoglobulin actually binds to a specific antigenic determinant. Antigen binding by antibodies is the primary function of antibodies and can result in protection of the host.  The valency of antibody refers to the number of antigenic determinants that an individual antibody molecule can bind. The valency of all antibodies is at least two and in some instances more.

Figure-3- Showing the general structure of Immunoglobulin and  structure of antigen binding cleft. Antigenic determinants are present on the surface of  antigen while the antigen binding sites are present in the antigen binding cleft made by both light chain and heavy chain

B. Effector Functions 

Frequently the binding of an antibody to an antigen has no direct biological effect. Rather, the significant biological effects are a consequence of secondary “effector functions” of antibodies. The immunoglobulins mediate a variety of these effector functions. Not every immunoglobulin will mediate all effector functions. Such effector functions include:

1. Fixation of complement – This results in lysis of cells and release of biologically active molecules

2. Binding to various cell types – Phagocytic cells, lymphocytes, platelets, mast cells, and basophils have receptors that bind immunoglobulins. This binding can activate the cells to perform some function.

Figure-4 showing the receptors present on the surface of macrophages to bind the antigen antibody complex

Some immunoglobulins also bind to receptors on placental trophoblasts, which results in transfer of the immunoglobulin across the placenta. As a result, the transferred maternal antibodies provide immunity to the fetus and newborn.

Figure- 5 showing the functions of different regions of the immunoglobulins


Immunoglobulin fragments produced by proteolytic digestion –

A.  Fab 
Digestion with papain breaks the immunoglobulin molecule in the hinge region before the H-H inter-chain disulfide bond Figure 6. This results in the formation of two identical fragments that contain the light chain and the VH and CH1 domains of the heavy chain.

Figure-6 showing the  site of action of Papain (a proteolytic enzyme).  Fab and Fc are the two fragments obtained by proteolytic cleavage.

Antigen binding – These fragments are  called the Fab fragments because they contained the antigen binding sites of the antibody. Each Fab fragment is monovalent whereas the original molecule was divalent. The combining site of the antibody is created by both VH and VL

B. Fc 
Digestion with papain also produces a fragment that contains the remainder of the two heavy chains each containing a CH2 and CH3 domain. This fragment was called Fc because it was easily crystallized.

Effector functions – The effector functions of immunoglobulins are mediated by this part of the molecule. Different functions are mediated by the different domains in this fragment (figure 5). 

Figure-7- showing the site of action of Pepsin on Immunoglobulin.

C. F(ab’)2 
Treatment of immunoglobulins with pepsin results in cleavage of the heavy chain after the H-H inter-chain disulfide bonds resulting in a fragment that contains both antigen binding sites (figure 7). This fragment is called F(ab’)2because it is divalent. The Fc region of the molecule is digested into small peptides by pepsin. The F(ab’)2binds antigen but it does not mediate the effector functions of antibodies.


A. Immunoglobulin classes 

The immunoglobulins can be divided into five different classes, based on differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a given class will have very similar heavy chain constant regions. 

1. IgG – Gamma  heavy chains

2. IgM – Mu  heavy chains

3. IgA – Alpha heavy chains

4. IgD – Delta  heavy chains

5. IgE – Epsilon  heavy chains

Immunoglobulin Subclasses 

The classes of immunoglobulins can de divided into subclasses based on small differences in the amino acid sequences in the constant region of the heavy chains. All immunoglobulins within a subclass will have very similar heavy chain constant region amino acid sequences. 

1. IgG Subclasses

a) IgG1 – Gamma 1  heavy chains

b) IgG2 – Gamma 2  heavy chains

c) IgG3 – Gamma 3  heavy chains

d) IgG4 – Gamma 4  heavy chains

2. IgA Subclasses

a) IgA1 – Alpha 1  heavy chains

b) IgA2 – Alpha 2  heavy chains

 Immunoglobulin Types 
Immunoglobulins can also be classified by the type of light chain that they have. Light chain types are based on differences in the amino acid sequence in the constant region of the light chain. 

1. Kappa light chains 

2. Lambda light chains 


A.  IgG

1. Structure

 All IgG’s are monomers (7S immunoglobulin). The subclasses differ in the number of disulfide bonds and length of the hinge region.

2. Properties

IgG is the most versatile immunoglobulin because it is capable of carrying out all of the functions of immunoglobulin molecules.

a) IgG is the major Ig in serum – 75% of serum Ig is IgG

b) IgG is the major Ig in extra vascular spaces

c) Placental transfer – IgG is the only class of Ig that crosses the placenta. Transfer is mediated by a receptor on placental cells for the Fc region of IgG. Not all subclasses cross equally well; IgG2 does not cross well.

d) Fixes complement – Not all subclasses fix equally well; IgG4 does not fix complement

e) Binding to cells – Macrophages, monocytes and neutrophils and some lymphocytes have Fc receptors for the Fc region of IgG.  A consequence of binding to the Fc receptors on such cells  is that the cells can now internalize the antigen better. The antibody prepares the antigen for killing by the phagocytic cells. The term opsonin is used to describe substances that enhance phagocytosis. (Coating of the surface of pathogen by antibody is called opsonization).IgG is a good opsonin. Binding of IgG to Fc receptors on other types of cells results in the activation of other functions.

Figure-8- showing the structure of Ig G 


1. Structure
 IgM normally exists as a pentamer (19S immunoglobulin) but it can also exist as a monomer. In the pentameric form all heavy chains are identical and all light chains are identical. Thus, the valence is theoretically 10. IgM has an extra domain on the mu chain (CH4) and it has another protein covalently bound via a S-S bond called the J chain. This chain functions in polymerization of the molecule into a pentamer.

2. Properties

a) IgM is the third most common serum Ig.

b) IgM is the first Ig to be made by the fetus and the first Ig to be made by a virgin B cells when it is stimulated by antigen.

c) As a consequence of its pentameric structure, IgM is a good complement fixing Ig. Thus, IgM antibodies are very efficient in leading to the lysis of microorganisms.

d) As a consequence of its structure, IgM is also a good agglutinating Ig . Thus, IgM antibodies are very good in clumping microorganisms for eventual elimination from the body.

e) IgM binds to some cells via Fc receptors.

f) B cell surface Ig 

Surface IgM exists as a monomer and lacks J chain but it has an extra 20 amino acids at the C-terminus to anchor it into the membrane . Cell surface IgM functions as a receptor for antigen on B cells.

 Figure-9- showing the structure of Ig M 


1. Structure

Serum IgA is a monomer but IgA found in secretions is a dimer as presented in Figure 10. When IgA exits as a dimer, a J chain is associated with it.

When IgA is found in secretions is also has another protein associated with it called the secretory piece or T piece; sIgA is sometimes referred to as 11S immunoglobulin. Unlike the remainder of the IgA which is made in the plasma cell, the secretory piece is made in epithelial cells and is added to the IgA as it passes into the secretions . The secretory piece helps IgA to be transported across mucosa and also protects it from degradation in the secretions.


Figure-10- showing the structure of Ig A 

2. Properties

a) IgA is the 2nd most common serum Ig.

b) IgA is the major class of Ig in secretions – tears, saliva, colostrum, mucus. Since it is found in secretions secretory IgA is important in local (mucosal) immunity.

c) Normally IgA does not fix complement, unless aggregated.

d) IgA can binding to some cells – PMN’s and some lymphocytes.


1. Structure

 IgD exists only as a monomer.

2. Properties

a) IgD is found in low levels in serum; its role in serum  is uncertain.

b) IgD is primarily found on B cell surfaces where it functions as a receptor for antigen.

 c) IgD does not bind complement.

Figure-11- showing the structure of Ig D 

E. IgE

1. Structure

IgE exists as a monomer and has an extra domain in the constant region.

2. Properties

a) IgE is the least common serum Ig since it binds very tightly to Fc receptors on basophils and mast cells even before interacting with antigen.

b) Involved in allergic reactions – As a consequence of its binding to basophils and mast cells, IgE is involved in allergic reactions. Binding of the allergen to the IgE on the cells results in the release of various pharmacological mediators that result in allergic symptoms.

c) IgE also plays a role in parasitic helminth diseases. Since serum IgE levels rise in parasitic diseases, measuring IgE levels is helpful in diagnosing parasitic infections. Eosinophils have Fc receptors for IgE and binding of eosinophils to IgE-coated helminths results in killing of the parasite.

d) IgE does not fix complement.

Figure-12- showing the structure of Ig E

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1- Name the major proteins of plasma.

(Albumin, Globulin and Fibrinogen)

2-Name the transport proteins

(Albumin, Lipoproteins, Prealbumin, Transthyretin, Retinol Binding protein, Thyroxin binding Globulin)

3-How many copper atoms can bind to one molecule of ceruloplasmin?


4-What is A: G ratio, what is its range in the normal health?                  

(1.2:1 to 1.5:1)

5-What is the most significant sign of hypoproteinemia?


6-Almost all proteins except Globulins are synthesized in the liver, True or false?


7-Name the negative phase proteins

(Albumin, Transthyretin, Transferrin etc.)

8-What are the different types of light chains?

( Kappa and Lambda)

9-Which immunoglobulin is the major antibody of primary immune response


10-What is the function of the secretory piece of the IgA?

(It protects the antibody from proteolytic digestion)

11-What is the actual meaning of Fc and Fab ?

(These are the two portions of immunoglobulins produced after proteolytic cleavage of immunoglobulin. Fc denotes fragment crystallisable and Fab denotes antigen binding fragment)

12-Which form of Ig M – monomeric or polymeric acts as a receptor on the surface of B lymphocytes.

( Monomeric form)

13-Which form (Alpha helical, Beta pleated sheet or triple helical) predominates in the structure of collagen?                                     

(Triple helical)

14-What are the different types of heavy chains present in different types if immunoglobulins?

(α, β,γ,δ, Σ)

15-What types of globin chains  are present in Fetal Hemoglobin?

(Two alpha and 2 Gamma)

16-What is methaemoglobin?

( Hb in which iron is in the oxidized form(Ferric form )

17-25 % of the structure of hemoglobin is in the alpha helical form- state true or false?

(False- 75% is in the alpha helical form)

18-Name the beta globulins of biological significance

(Transferrin, Haemopexin, Complement etc)

19-What is the nature of ceruloplasmin?

(Alpha 2 globulin)

20-What is the function of Transferrin?

(Transfer of iron)

21-What is the function of fibrinogen?

(Blood clotting and viscosity)

22-What is the clinical significance of C- reactive protein ?

(Acute phase protein, activates complement, also helps in the formation of haem)

23-What is meant by opsonization?

(Coating the surface of antigen by antibodies)

24-What is the difference between monoclonal and polyclonal antibodies?

(Monoclonal means antibodies of only one specificity while polyclonal means antibodies of different specificities)

25-Hepato lenticular degeneration is observed due to deficiency of which plasma protein?


26-What is the function of complement protein ?

(These are defense molecules present in the plasma in the inactive form, required for pathogenic killing)

27-Enumerate the causes of hypo Albuminemia?

(Hypovolemia, mal nutrition, cirrhosis of liver, losses from the body ),

28-Give two causes of hyperproteinemia

(Hemoconcentration, malignancies, chronic infections)

29-What is class switching?

(The switch from one class of immunoglobulin to another class is called class switching)

30-How are the light chain and heavy chains linked together?

 ( By disulphide linkages)

31-What is the function of carbohydrate in the structure of immunoglobulins?

( It is required for the secretion of antibodies by the plasma calls)

32-Which antibody is called as the mucosal barrier?

( Ig A)

33-Which antibody is called as the Millionaire molecule?

 ( Ig M )

34-How is the rate of catabolism of Ig G affected by its serum concentration?

( It is a direct relationship, more the concentration more is the rate  of catabolism

 35- How many polypeptide chains are present in the structure of myoglobin?


36-Which out of the two (Myoglobin and hemoglobin) has more affinity for Oxygen?


37-Name two proteins that bind thyroid hormone

(Thyroxin binding protein and Transthyretin)

38-What will be the effect of excessive vomiting on plasma protein concentration ?

( It will result in hyperproteinemia due to hemoconcentration)

39-In a chronic alcoholic patient plasma protein concentration should be lower than normal or higher?

(Lower than normal)

40- What is the function of Transcobalamine?

(Transporter of B12)

41-What are Bence jone’s proteins?

These are light chain Immuno globulins excreted in the urine of a patient suffering from multiple myeloma.

 42– What are the clinical features observed in a patient of multiple myeloma ?

(Weight loss, punched out lesions, anemia , increased frequency of infections)

43-What are the component chains in HbA1?

( 2 alpha and 2 delta)

 44 What is the cause of emphysema in alpha 1 anti trypsin deficiency?

(Inactivated Elastase which causes damage to the lung tissues)


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1- The deficiency of which plasma protein is responsible for Wilson’s disease ? 


2-Which immunoglobulin is pentameric in structure?                    

(Ig M)

3-Which plasma protein is a transporter of free fatty acids?


4-Which protein acts as reservoir of oxygen?                        


5-What is the normal level of Fibrinogen in the blood?      

(300mg %)

6-Which Immunoglobulin is present at the mucosal surfaces?

( IgA)

7-Complement activation is a function of which part of the Immunoglobulin?

(Fc segment)

8-Which antibody is the first to be synthesized in a fetus ?

(Ig M)

9-What is the function of Hinge region of an immunoglobulin?

(The hinge region confers flexibility and allows both Fab arms to move independently, thus helping them to bind to antigenic sites that may be variable distances apart (eg, on bacterial surfaces).)

10-Name the storage protein of iron                            


11-Name a plasma protein that binds extra corpuscular Hb        


12- γ Globulins are synthesized in the plasma cells- State true or false


13-What is the nature of apoprotein present in HDLc?                  

(α1- globulin)

14-What is specified by CL   in the structure of immunoglobulin?

(Constant region of light chain)

15-What are the consequences of α1- Antitrypsin deficiency?

(Emphysema and cirrhosis of liver)

16-Name a plasma protein which acts as a transporter of Iron


17-Maximum contribution to the buffering capacity of plasma proteins is by- ?

(Albumin- due to the presence of histidine residues )

18-Maximum contribution to the viscosity of plasma is by—–?

(Fibrinogen- Since it is an elongated molecule)

19-What is Analbuminemia?

( Congenital absence of Albumin in the plasma)

20- The plasma level of gamma globulins is decreased in chronic liver  diseases True or false ?

(False- The level of gamma globulins is increased in chronic liver diseases)

21-What is the clinical significance related with Alpha feto protein?

  (Its plasma level is increased in liver cell carcinoma and teratoblastomas)

22-What is the function of Alpha 1 acid Glycoprotein?

( Acute phase protein and transporter of Progesterone)

23- What is the significance of the variable region of the immunoglobulins and why is it so-called variable region?

( It is variable in amino acid sequence and is involved in antigen binding)

24- Which plasma protein is a transporter of bilirubin?    


25- What is meant by acute phase proteins?

(Acute phase proteins are those proteins, the synthesis and thus the plasma level of which are increased in response to inflammation or tissue damage.)

26–What is the difference between plasma and serum?

(Plasma contains clotting factors, while serum lacks them)

27-Out of Albumin, hemoglobin and immunoglobulin, which one has the least molecular weight?                                             


28-What is the difference between Haemopexin and hemoglobin?

(Haemopexin binds free haem while Haptoglobin binds free hemoglobin.)

29-What is the function of IgD?

(It acts as a receptor on the surface of B lymphocytes)

30-Name the Acute phase proteins

(Alpha 1 Antitrypsin, Alpha 1 acid glycoprotein, Haptoglobin, C-reactive protein)

31-What is the actual meaning of C-reactive protein, what does C mean?

(CRP, so-named because it reacts with the C polysaccharide of pneumococci)

32-Out of lipoproteins, immunoglobulins and Albumin, which one  is a simple protein ?     


33-Name the plasma proteins involved in the clotting of blood?

(Fibrinogen and clotting factors)

34-Name the defense proteins of plasma

(Immunoglobulins, complement proteins and Beta 2 microglobulin)

35-How is copper transported in the blood?

(It is transported complexed with ceruloplasmin and Albumin)

36-Kayser-Fleischer ring is diagnostic of which disease?

(Wilson disease)

37-What types of enzyme activities are associated with ceruloplasmin ?

(It has copper dependent Ferro- oxidase activity, it oxidizes iron  from ferrous to ferric form

38-Out of the following proteins which protein has mainly alpha helical structure-

(Collagen, immunoglobulin, myoglobin)               


39-What is the chemical nature of Bence jone’s proteins?

(Light chain of immunoglobulins)                             

40-Name the commonly occurring haemoproteins

(Hemoglobin, Myoglobin, Cytochromes, Peroxidase and Tryptophan Pyrrolase)

41-How does smoking inactivate the Alpha 1 Antitrypsin protein?

(Smoking oxidizes this methionine to methionine sulfoxide and thus inactivates it. As a result, affected molecules of alpha 1-antitrypsin no longer neutralize proteases.)

42-Name three conditions of hyperproteinemia

(Hemoconcentration, chronic infections and malignancies)

43-What is the significance of M band , where is it located ?

(M band is present between beta and gamma globulin regions on electrophoresis of plasma proteins and is diagnostic of Multiple myeloma)

44- How many polypeptides are present in the structure of globin part of hemoglobin ?


45-Which amino acid contributes maximally to the structure of collagen molecule?


46- Which immunoglobulin has the cytophilic property?

( Ig E)

47-The number of antibody secreting  plasma cells are decreased in Multiple myeloma that is why there is impaired humoral immune response . True or false?

(False- The number of plasma cells secreting antibodies are increased but these are abnormal and useless antibodies not targeted against any antigen, but the actual humoral response against a specific antigen is decreased.)

48- Which antibody is considered the most potent agglutinating antibody?


49-Which protein is precipitated by full saturation with Ammonium sulphate?


50-What is Pre albumin? Why is to so named? Is it a precursor of Albumin?

( Ii is a plasma protein and not a precursor, it is so named because of its faster electrophoretic migration in the electric field).


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1) – A mutation has changed an isoleucine residue of a protein to Glutamic acid, which statement best describes its location in a hydrophilic exterior-

a) On the surface since it is hydrophilic in nature

b) In side the core of the protein since it is hydrophobic in nature

c) Any where inside or outside

d) Inside the core of protein since it has a polar but uncharged side chain

2) – Glycine and proline are the most abundant amino acids in the structure of-

a) Hemoglobin

b) Myoglobin

c) Insulin

d) Collagen

3) – Some proteins contain additional amino acids that arise by modification of an amino acid already present in a peptide, examples include-

a) 4 -hydroxy proline

b) 5- hydroxy Lysine

c) Gamma Amino Butyric Acid

d) All of the above

4) – Choose the incorrect statement out of the following-

a) Only L amino acids are found in the biological system

b) Glycine is optical inactive

c) Tyrosine is a modified amino acid

d) Seleno cysteine is 21 st amino acid

5) – Choose a nano peptide out of the following-

a) Oxytocin

b) Vasopressin

c) Bradykinin

d) All of the above.

6) – Which out of the following amino acids carries a net positive charge at the physiological p H ?

a) Valine

b) Leucine

c) Isoleucine

d) None of the above 

7) – Which out of the following amino acids is a precursor for a mediator of allergies and inflammation?

a) Histidine

b) Tyrosine

c) Phenyl Alanine

d) Tryptophan

8) – Mother of a mal nourished child has been instructed to include a complete protein in diet for her child, which out of the following proteins should be recommended?

a) Pulses

b) Wheat

c) Soy Protein

d) Milk

9) – All of the below mentioned amino acids can participate in hydrogen bonding except one –

a) Serine

b) Cysteine

c) Threonine

d) Valine

10) – All of the following amino acids are both glucogenic as well as ketogenic except –

a) Isoleucine

b) Leucine

c) Tyrosine

d) Phenyl alanine

11) – Which out of the following amino acid is a precursor of niacin (Vitamin)?

a) Tyrosine

b) Threonine

c) Tryptophan

d) Phenylalanine

12) – The greatest buffering capacity at physiological p H would be provided by a protein rich in which of the following amino acids?

a) Serine

b) Cysteine

c) Alanine

d) Histidine

13) – Which of the following peptides is cyclic in nature-?

a) Glutathione

b) Gramicidin

c) Met encephalin

d) Leuencephalin

14) – Which out of the following is not a fibrous protein?

a) Carbonic anhydrase

b) Collagen

c) Fibrinogen

d) Keratin

15) -Which of the following amino acid is a limiting amino acid in pulses?

a) Leucine

b) Lysine

c) Methionine

d) Glutamine

16)- Which out of the following is not a haemo protein ?

a) Catalase

b) Myeloperoxidase

c) Glutathione peroxidase

d) Aconitase

17) – All the below mentioned proteins are metalloproteins except-

a) Carbonic anhydrase

b) Xanthine oxidase

c) Lactate dehydrogenase

d) Superoxide dismutase                                                                                                       

18) – Which out of the following is a peptide antibiotic?

a) Erythromycin

b) Gramicidin

c) Ciprofloxacin

d) Tetracycline

19) – Choose the Anticancer peptide out of the following-

a) Bleomycin

b) Methotrexate

c) Cytosine Arabinoside

d) Dideoxy Inosine

20) – Which of the following amino acids is most compatible with an α- helical structure?

a) Tryptophan

b) Alanine

c) Leucine

d) Proline

21) – The highest concentration of cystine can be found in-

a) Melanin

b) Keratin

c) Collagen

d) Myosin

22) – In scurvy, which amino acid that is normally part of collagen is not synthesized?

a) Hydroxy Tryptophan

b) Hydroxy Tyrosine

c) Hydroxy Alanine

d) Hydroxy Proline

23) – A child with tall stature, loose joints, and detached retinas is found to have a mutation in collagen. Which of the following amino acids is the recurring amino acid most likely to be altered in mutations that distort collagen molecules?

a) Glycine

b) Tyrosine

c) Tryptophan

d) Tyrosine

24) – Which one of the following amino acids may be considered a hydrophobic amino acid at physiological p H of 7.4?

a) Isoleucine

b) Arginine

c) Aspartic acid

d) Threonine

25) – Which of the characteristics below apply to amino acid Glycine?

a) Optically inactive

b) Hydrophilic, basic and charged

c) Hydrophobic

d) Hydrophilic, acidic and charged

26) – Which of the following amino acids in myoglobin, a globular protein, is highly likely to be localized within the interior of the molecule?

a) Arginine

b) Valine

c) Aspartic acid

d) Lysine

 27) – Which of the amino acids below is the uncharged derivative of an acidic amino acid?

a) Cystine

b) Tyrosine

c) Glutamine

d) Serine

28) – Choose the correct category for milk protein casein out of the following-

a) Nucleoprotein

b) Phospho protein

c) Lipoprotein

d)  Glycoprotein


1-      a

2-      d

3-      d

4-      c

5-      d

6-      d

7-      a

8-      d

9-      d

10-   b

11-   c

12-   d

13-   b

14-   a

15-   c

16-   d

17-   c

18-   b

19-   a

20-   b

21-   b

22-   d

23-   a

24-   a

25-   a

26-   b

27-   c

28-   b


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1-      Haemoglobin and collagen are proteins with diverse functions. Describe how the structures of proteins can be correlated with their functions.

2-      Define protein denaturation. Explain why, when insulin or majority proteins are subjected to denaturation and renaturation conditions, they regain only a few percent of their original activities.

3-      What is the basis of the classification of amino acids? Give one example for each class of amino acids.

4-      What is protein denaturation? Explain the significance of the denaturation-renaturation experiments on ribonuclease.

5-      What are the salient features of an alpha helix? Name the amino acids that destabilize this structure.

6-      Name two modified amino acids found in proteins and state their biological functions.

7-      Discuss fully the primary, secondary, tertiary and quaternary structure of proteins. Illustrate your answer with suitable example

8-      Distinguish between a simple and a conjugated protein. Illustrate your answer with suitable examples.

9-      What are the buffering groups present in a protein at physiological pH? Show how these groups help to contribute to buffering capacity.

10-   Draw the structure of any ammo acids as: (i) zwitterion (ii) cationic form (iii) anionic form

11-   Draw the structure of a dipeptide. Use R to represent the side chain of an amino acid.

12-   Describe the special roles of glycine and proline in protein structure.

13-   What is the stereochemical difference between D-alanine and L-alanine?

14-   What are the main characteristics of globular and fibrous proteins? Give an example of each of these proteins.

15-   Explain how a proline residue in polypeptide chain interrupts the alpha-helical structure.

16-   What are standard or primary amino acids? Give examples of non standard amino acids.

17-   What is iso electric p H ? What are the commercial applications of iso electric p H?

18-   Justify the statement, “Primary structure guides the formation of secondary and tertiary structure”, give example in support of your answer.

19-   What is protein misfolding? Give examples and discuss the clinical significance of protein misfolding.

20-   How is a peptide bond formed between the two amino acids? Discuss the characteristics of a peptide bond.

21-   Enlist the biologically important peptides; Give a brief account of the functions of Glutathione.

22-   Enlist the important functions of amino acids.

23-   What are the various ways by which proteins can be classified? Give examples of each category of proteins.

24-   Compare and contrast the structural features of α helix and β pleated sheets. Give examples of proteins having predominance of these structures.

25-   What is a domain? How is it formed, what kind of forces stabilize its structure?

26-   Give an account of the properties of amino acids, state the clinical significance if any of such reactions.

27-   An 80- year-old male was brought for consultation to  a Medical OPD with the chief complaints of loss of memory and disorientation from the past few months. He was diagnosed with Alzheimer disease. Discuss the biochemical basis, clinical symptoms and the prognosis of this disease.

28-   “Primary structure is guided by information on DNA. A single nucleotide change on DNA can alter the information and thus the sequence of amino acids in a peptide chain with the resultant loss of partial or total functional capacity of the protein”. Comment on the statement.

29-   Enlist the names of the tests performed for detection of specific amino acids in a sample.

30-   Give a brief account of the agents which can bring about protein unfolding? Discuss the biological or clinical aspect of protein denaturation.

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

Case Details

An 80 –year-old man presented with impairment of brain functions, alterations of mood and behavior.His family reported that he was having progressive disorientation and memory loss over the past 6 months.  He had trouble handling money and paying bills. He repeated questions, took longer to complete normal daily tasks, had poor judgment, and had developed mood and personality changes.

There was no family history of dementia.The routine blood, urine and C.S.F analysis did not reveal much.After a computerized tomography (CT) scan and the histopathological examination of the brain tissue, the patient was diagnosed to be having Alzheimer disease.

What is the defect in this disease?

How is the diagnosis done and what is its prognosis?

Case discussion

Alzheimer’s disease

Basic Concept

Alzheimer’s disease is defined as premature aging of the brain, usually beginning in mid-adult life and progressing rapidly to extreme loss of mental powers—similar to those, seen in very, very old age.

Clinical features

Alzheimer’s disease is a progressive and fatal neurodegenerative disorder that results in impairment of a person” ability to perform routine activities and the patient finally enters in to a vegetative state with no comprehension to the outside world. The disease runs in four stages, pre dementia. Mild dementia, moderate dementia and advanced dementia.

Although the course of Alzheimer’s disease is unique for every individual, there are many common symptoms.

The earliest observable symptoms are often mistakenly thought to be ‘age-related’ concerns, or manifestations of stress. In the early stages, the most commonly recognized symptom is memory loss, such as difficulty in remembering recently learned facts.

As the disease advances, symptoms include confusion, irritability and aggression, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as their senses decline.

Gradually, bodily functions are lost, ultimately leading to death.


 Alzheimer’s disease is the most common form of dementia in the elderly and about 5 million people in the United States are estimated to be afflicted by this disorder. The percentage of persons with Alzheimer’s disease approximately doubles with every five years of age, with about 1 percent of 60-year-old and about 30 percent of 85-year-olds having the disease.

Biochemical defect

Alzheimer’s disease has been identified as a protein misfolding disease, caused by accumulation of abnormally folded A-beta and tau proteins in the brain. Plaques are made up of small peptides, 39–43 amino acids in length, called beta-amyloid (also written as A-beta or Aβ). Beta-amyloid is a fragment from a larger protein called amyloid precursor protein (APP), a transmembrane protein that penetrates through the neuron’s membrane.

APP is critical to neuron growth, survival and post-injury repair.

 In Alzheimer’s disease, an unknown process causes APP to be divided into smaller fragments by enzymes through proteolysis. One of these fragments gives rise to fibrils of beta-amyloid, which form clumps that deposit outside neurons in dense formations known as senile plaques.(Figure-1)

AD is also considered a tauopathy due to abnormal aggregation of the tau protein. Every neuron has a cytoskeleton, an internal support structure partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell to the ends of the axon and back. A protein called tau stabilizes the microtubules when phosphorylated, and is therefore called a microtubule-associated protein. In AD, tau undergoes chemical changes, becoming hyperphosphorylated; it then begins to pair with other threads, creating neurofibrillary tangles and disintegrating the neuron’s transport system.

Amyloid plaques and Neuro fibrillary tangles

Figure-1 -showing amyloid plaques and Neuro fibrillary tangles in Alzheimer disease

AD, is also associated with a decrease in the cerebral cortical levels of several proteins and neurotransmitters, especially acetyl choline; there is reduction in nor epinephrine levels also in brain stem nuclei.

ApoE 4 allele has a strong association with AD in the general population, ApoE is present in the neuritic amyloid plaques of AD, and it may also be involved in neurofibrillary tangle formation, because it binds to tau protein.

Accumulation of aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell’s calcium ion homeostasis, induces programmed cell death (apoptosis). Aβ selectively builds up in the mitochondria in the cells of Alzheimer’s-affected brains, and it also inhibits certain enzyme functions and the utilization of glucose by neurons.

Brain atrophy in Alzheimer's disease

Figure-2 showing brain atrophy


The vast majority of cases of Alzheimer’s disease are sporadic, meaning that they are not genetically inherited although some genes may act as risk factors. On the other hand around 0.1% of the cases are familial forms of Autosomal-dominant inheritance, which usually have an onset before age 65.

The best known genetic risk factor is the inheritance of the ε4 allele of the Apo lipoprotein E (APOE). Between 40 and 80% of patients with AD possess at least one apoE4 allele. The APOE4 allele increases the risk of the disease by three times in heterozygotes and by 15 times in homozygotes


Alzheimer’s disease is usually diagnosed clinically from the patient’s history, collateral history from relatives, and clinical observations, based on the presence of characteristic neurological and neuropsychological features and the absence of alternative conditions.

Assessment of intellectual functioning including memory testing can further characterize the state of the disease.

Advanced medical imaging with computed tomography (CT) or magnetic resonance imaging (MRI), and with single photon emission computed tomography (SPECT) or positron emission tomography (PET) can be used to help exclude other cerebral pathology or subtypes of dementia.

Alzheimer’s disease is characterized by loss of neurons and synapses in the cerebral cortex and certain sub cortical regions. This loss results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.(Figure-2) Studies using MRI and positron emission tomography have documented reductions in the size of specific brain regions in patients as they progressed from mild cognitive impairment to Alzheimer’s disease, and in comparison with similar images from healthy older adults.

A histopathological confirmation including a microscopic examination of brain tissue is required for a definitive diagnosis. Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in brains of those afflicted by AD.(Figure-1)


There is no cure for Alzheimer’s disease; available treatments offer relatively small symptomatic benefit but remain palliative in nature. Current treatments can be pharmaceutical, psychosocial and care giving.

Four medications are approved by the U.S. Food and Drug Administration to treat AD. Donepezil, rivastigmine, and galantamine) are used to treat mild to moderate AD (Donepezil can be used for severe AD as well). Memantine is used to treat moderate to severe AD. These drugs work by regulating neurotransmitters. They may help maintain thinking, memory, and speaking skills, and help with certain behavioral problems. However, these drugs don’t change the underlying disease process and may help only for a few months to a few years.


Individual prognosis is difficult to assess, as the duration of the disease varies. AD develops for an indeterminate period of time before becoming fully apparent, and it can progress undiagnosed for years. The mean life expectancy following diagnosis is approximately seven years. The earlier the age at onset the higher the total survival years, life expectancy is part Men have a less favorable survival prognosis than women.

Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1-Give an example of reversible denaturation

(Denaturation of Ribonuclease by urea)

 2. Give example of a circular peptide.

(Gramicidin S)

 3-What is the difference between Salting in and Salting out?

(Salting in is addition of a pinch of salt to increase the solubility of a protein, while salting out is addition of excess of salt to precipitate it out)

4. Name the proteins containing alpha helical structure predominantly.

(Hemoglobin, Myoglobin etc)

5. Name the super secondary structures

(Greek key, beta meanders, Beta alpha beta)

6. Name the respiratory proteins

(Hemoglobin, Myoglobin, cytochromes)

 7. What is the class of Zein protein?

(Poor protein- it lacks Tryptophan and Lysine)

 8. Name the contractile proteins 

( Actin, Myosin, flageller proteins)

 9-What are the features of isoelectric pH?

(Decrease in solubility, electric charge, Electrophoretic migration, loss of biological activity)

 10-What is the basis of protein precipitation by organic solvents?

(Decrease in dielectic constant of the medium)

11-What is the difference between flocculum and coagulum?

(Flocculum is a reversible state of denaturation while coagulum is a an irreversible state of denaturation)

12-What are the forces that stabilize the alpha helical structure?

(Hydrogen and Vander waals forces mainly)

13-What is the basis of cauterization by silver nitrate during surgery to control bleeding?

(Silver nitrate is a heavy metal salt and by causing precipitation of proteins seals the oozing points of the blood vessels)

14-What is meant by a domain?

(Domain is a term used to denote a compact globular functional unit of a protein)

15-Why is Glutathione called a pseudo peptide?

(In glutathione instead of alpha carboxyl group, the gamma carboxyl participates in the peptide bond formation)

16-Covalent forces stabilize the tertiary structure in a protein- True or false?

(False- the non covalent forces stabilize the tertiary structure in a protein)

17- Which tests should be carried out for the detection of Tryptophan in a given solution?  

(Xanthoproteic and Hopkins Cole test)

18- Which amino acids contribute towards ionic interactions?

(Positively charged amino acids like Arginine , Lysine and negatively charged amino acids like Aspartic acid and Glutamic acid)

19- Which protein is precipitated by full saturation with Ammonium sulphate?


20- What is the relationship of amount of salt required and the molecular weight of a protein?

(More the molecular weight and lesser is the amount of salt required by the protein and vice versa)

21-What are the functions of proteins?

(Nutritive, buffering, defense, viscosity, osmotic pressure, enzymes, hormones etc)

22-Name mono amino dicarboxylic acids

 (Aspartic and Glutamic acid)

 23-Name heterocyclic amino acids

 (Tryptophan and Histidine)

 24-Name the 21st and 22 nd amino acid

 (Seleno cysteine and Pyrrolysine)

 25-Which amino acids are involved in forming N- Glycosidic linkages?

 (Asparagine and Glutamine)

26-Name the semi essential amino acid

(Arginine and Histidine)

27-Which amino acid acts as the precursor of vitamin Niacin?


28-Name the amino acids with a non polar side chain

(Alanine, Valine, Leucine Isoleucine, Methionine, Phenyl Alanine)

29-Which protein structure determines the relationship of amino acids which are 3-4 residues apart ?

 (Tertiary structure)

30-Which test will be negative for a protein lacking tryptophan ?

 (Hopkins cole test)

 31-Name the essential amino acids

( Valine, Leucine, Isoleucine, lysine, Phenylalanine, Methionine and Threonine)

 32-Which amino acid is optically inactive ?


 33-Which amino acid is abundantly present in prolamines ?


 34-Which protein is mostly found attached to DNA?


 35-Name the amino acids which are both glucogenic as well as ketogenic

(Isoleucine. Phenyl Alanine, Tyrosine and Tryptophan)

35-Name a specific test for the detection of alpha amino acids

(Ninhydrin test)

 36-Name a  specific test for the detection of cysteine

(Lead acetate test)

37-Covalent bond is formed at which level of protein’s structural organization?

(Primary structure)

38-Name the peptide hormones

 (ACTH, TRH, FSH, Glucagon, PTH, ADH, Oxytocin, Secretin, Pancreozymin, Cholecystokinin)

 39-What is the effect on the biological activity of a protein when exposed to UV light ?

 ( It will lose its biological activity since it will be denatured)

 40-Give two examples of protein misfolding causing disease?

 ( Prion’s and Alzheimer disease)

41-What is the class of casein ?

 (Class 1- complete protein) 

42-What are the forces that stabilize quaternary structure of a protein ?

 (Mainly non covalent)

 43-Which amino acid acts as the best buffer of the plasma?


 44-What will be the product of decarboxylation of Tyrosine?


 45-Why can’t albumin and majority proteins acquire the native configuration upon denaturation?      

 (Chaperones and other proteins assisting proper folding are not there)

 46-What are Beta bends?

 (Short loops to turn the direction of the beta sheets?

 47-What are the forces that stabilize the beta bends?

 (Hydrogen and electrostatic)

 48-Name a peptide to regulate the volume of urine excreted?


 49-Which protein is present in the tendons and cartilages? 


 50-Name the storage proteins

 Ferritin, ceruloplasmin)


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1- What is the nature of a prosthetic group in a lipoprotein?

 (Lipoprotein is a conjugated protein with lipid as a prosthetic group)

 2- What is the significance of Sakaguchi test?

 (This test is undertaken for the detection of Arginine)

 3- What is the distance traveled per turn in an alpha helix?

 (0-54 nm)

 4- Name an imino acid.

 (Proline, hydroxy proline)

 5-Choose the chromo protein out of the following-

 Collagen, Keratin, hemoglobin                       


 6-Carbonic anhydrase is an example of simple or conjugated protein?

 (It is a conjugated protein, with metal as th prosthetic group)

 7- Name a peptide which acts as an artificial sweetener.


 8- Name the agents which can bring about denaturation of proteins

 (Heat, acids, alkalis, heavy metal salt, UV light, vigorous shaking etc)

 9- Name a tripeptide which acts a reducing agent in the tissues.


 10- Name a peptide which acts as vasoconstrictor


 11- Name the amino acid which is deficient in pulses


 12- Choose the odd one out- Collagen, Elastin, Keratin, Histones

 (Histones- The rest three are scleroproteins)

 13- Name two nano peptides

 (Oxytocin, Vasopressin)

 14- Name two globular proteins

 (Hemoglobin, Myoglobin)

 15-Which test should be undertaken for the detection of cysteine in a protein solution?

 (Lead acetate test)

 16-What is the nature of peptide bond- Single, double or partial double bond ?

(Partial double bond)

 17- Out of all the primary amino acids which amino acid gives yellow color on Ninhydrin test?                  

 (Proline and hydroxy proline )

 18- Histamine is formed from Histidine by-

 Deamination, decarboxylation or transamination


 19- Name two non alpha amino acid

 (GABA, beta Alanine, Delta amino Levulinic acid)

 20- Choose the odd one out-

 Aspartic acid, lysine, Arginine, Cysteine                   

 (Cysteine- Amino acid with uncharged side chain at physiological p H

 21- Choose the odd one out-

Tyrosine, Tryptophan, Threonine                   

 (Tyrosine- non essential Amino acid from the nutritional perspective or threonine if considered non aromatic amino acid)

 22- Name a purely ketogenic amino acid             


 23- Name a peptide used as an anticancer drug            


 24- Name the defense proteins                                     

 (Complement, immunoglobulin)

 25- Choose the odd one out- Silk fibroin, Hemoglobin, Carbonic anhydrase

 (Hemoglobin- The rest are proteins with beta pleated sheet

 26- The proteins with a carbohydrate content > 10 % are called as Mucoproteins- True or false?         


 27- The most abundant amino acid in keratin?             


 28- The most abundant amino acid in Collagen—-?      


 29- Xanthoproteic test does not specify for—- ?

 Tyrosine, Tryptophan, Serine               


 30- Give the characteristics of a peptide bond in one line-

 (Rigid, partial double bond, Trans and stable)


31-Name the branched chain amino acids 

 (Valine, Leucine, iso Leucine)

 32-Choose the hydrophobic amino acid out of the followings-

 Aspartic acid, Arginine, Serine, Isoleucine


 33-Which amino acid acts as Methyl group donor?


 34- What is the difference between Deamination and Transamination?

(Deamination is the removal of amino group of the amino acid while Transamination is the transfer of amino group from one  donor amino acid to an acceptor keto acid for the formation of a new amino acid)

 35- Out of the 20 amino acids which amino acids participate in the formation of phosphoproteins

 (Serine and Threonine)

 36- Formation of carbamino compound for the transportation of carbon dioxide is a property of amino group, carboxyl group or both groups?

 (Amino group)

 37- Hopkins Cole test is a confirmatory test for which amino acid?


 38- How many peptide bonds are there in a tripeptide?


 39- The alpha helix is right or left handed?         

 (Right handed)

 40- What is the direction of hydrogen bonds in the beta pleated sheet structure?

 (Perpendicular to the axis)

 41-What is the direction of beta pleated sheets in flavodoxin?


 42-Name the most abundant protein in mammals        


 43-Name a defect in the primary structure responsible for the causation of a disease

 (Sickle cell disease)

 44-What is the defect in Alzheimer disease?

 (Protein misfolding leading to formation of insoluble protein aggregates)

 45-What is the isoelectric p H of casein?


 46- What is the effect on the solubility of a protein upon denaturation?

 (Solubility decreases upon denaturation)

 47- Name the lipo proteins of biological significance

 (Chylomicrons, VLDL, LDL, HDL)

 48- Which amino acid is lacking in cereals?

 (Cereals lack Lysine)

 49- Which amino acid forms disulphide linkages between two polypeptide chains in oligomeric proteins?                       


 50- Which peptide is used in clinical practice to induce uterine contractions?


Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!

1. Why are amino acids called as Amino acids?

(Since they have an amino group and an acid group i.e. Carboxyl group which is ionized at the physiological p H and behaves as a proton donor and is thus an acid)

 2- What is meant by primary amino acids?

(Those amino acids which have a genetic information on the DNA for their synthesis are called as Primary or standard amino acids)

3- What is the linkage between the amino acids in a peptide?

(The amino acids are linked together by a peptide bond which is an anhydrous linkage between the amino acids)

4- Name the amino acids which are derived or modified after translation but are not incorporated in to the tissue proteins.

 (Homocysteine, GABA, Argino succinic acid, Ornithine, Citrulline, etc)

5- Define Denaturation

 ( It is the loss of secondary , tertiary or quaternary structure( if present ) of a protein on exposure to heat, UV light, acids, alkalies, heavy metal salts or even by vigorous shaking, the primary structure is left intact)

6-What is meant by a complete protein, give an example of a complete protein?

( A Complete protein contains all the essential amino acids in an appropriate amount  required for growth, repair and maintenance of body weight.  Example -Egg protein)

7- Give an example of a protein with axial ratios >10:1

(Fibrinogen, keratin, collagen )

8-How many amino acids can be accommodated in one turn of alpha helix?

(3.4 amino acids)

 9- What are chaperones?

 (These are the proteins which participate in the proper folding of the proteins)

10- What is the defect in “transmissible spongiform encephalopathies’?

(These are included under the category of Prion’s diseases and are fatal neurodegenerative diseases characterized by spongiform changes, astrocytic gliomas, and neuronal loss resulting from the deposition of insoluble protein aggregates in neural cells. The protein aggregates are formed of misfolded proteins.)

11-What is the difference between a homodimer and a heterodimer?

(Homodimer contains two copies of the same polypeptide chain, while in a heterodimer the polypeptides differ)

12-What are amphipathic helices?

(The alpha helices having predominantly hydrophobic R groups on one side of the axis of the helix and predominantly hydrophilic ones on the other side are called amphipathic helices)

13-All the amino acids except——- have a chiral centre.


14-What is meant by isoelectric  p H ?

 ( It is the p H at which amino acid carries no net electrical charge)

15-Proteins contain only D-amino acids, for which a left handed alpha helix is by far the more stable,  thus only left-handed helices are present in proteins. True or false?

 (False –Proteins contain only L-amino acids, for which a right-handed alpha helix is by far the most stable, and only right-handed alpha helices are present in proteins)

16-Give examples of metalloproteins-

( Alcohol dehydrogenase, glutamate dehydrogenase, Xanthine oxidase  etc. are the examples of metalloproteins

17-Give examples of non standard amino acids which are incorporated in to tissue proteins.

( Hydroxy proline, hydroxy lysine )

18– What is meant by zwitterion ?

( It is the form of amino acid present at its isoelectric p H,  both positive  and negative charges are there but the net charge is zero)

19-Name an indole ring containing amino acid-


20- Name the peptides which act as gastro intestinal hormones-

( Secretin, pancreozymin and cholecystokinin)

21- Name the amide group containing amino acids

(Asparagine, Glutamine)

22- What are derived proteins ?

(Proteoses, peptones and peptides etc, the product of digestion and denaturation are called as derived proteins )

23- Give two examples of antibiotic peptides

(Polymyxin, Penicillin, etc )

24-What is the difference between cysteine and cystine ?

( Two cystine residues are joined together by a disulfide bridge to from cystine )

25- What are histones? 

( Histones are simple proteins which can bind with DNA to form nucleoproteins, generally they are rich in basic amino acids like Arginine and lysine )

26- Which amino acid disrupts the alpha helical structure of the proteins ?

( Proline and hydroxy proline )

27- Name the components of Glutathione

(Glutamic acid, cysteine and glycine )

28- Name two proteins with a quaternary structure

( Immuno globulins, Hemoglobin, CPK , LDH etc )

29- What are brain peptides ?

( Met encephalin and Leuencephalin)

30- Name a Phospho protein

(Casein, Ovovitellin)

31-What is the product formed after decarboxylation of an amino acid ?

( Amines are formed after decarboxylation of amino acids- like Tryptamine, histamine Tyramine etc)

32-Name the sulphur-containing amino acids-

(Cysteine, cystine and Methionine)

33-Choose the aromatic amino acid out of the following-

Arginine, Histidine, lysine and Tyrosine —— (Tyrosine)

34-Choose an amino acid that does not participate in the alpha helical formation-

Methionine, tryptophan, serine, cysteine——

( Tryptophan )

 35- Millon’s reaction is specific for——- ?        

( Tyrosine )

36- Out of the followings which amino acid is not present in the proteins?

β- Alanine, Histidine, Glycine                    

(β- Alanine)

 37- Name a peptide which acts as a smooth muscle relaxant

( Bradykinin)

38-   What is the nature of prosthetic group in Ceruloplasmin ?

(Copper- It is metalloprotein)

 39- What is a nutritionally poor protein ?Give an example-

( A protein which lacks many essential amino acids is called a poor protein, E.g.- Gelatin

 40- Which protein is abundantly present in hair?     

(Keratin )

41-What is the significance of Biuret test?

 ( It is for the detection of proteins and peptides. Dipeptides and amino acids do not give this test positive, more than two peptide bonds are required for this test to be positive )

42- What is the nature of casein, the milk protein?

( It is a Phospho protein- A conjugated protein)

 43- What is the axial ratio in fibrous proteins?

 ( > 10:1)

 44- In proteins the alpha helical and beta pleated sheet structures are examples of-

Primary, secondary or tertiary structure ?            

( Secondary)

 45- Name an Imidazole ring containing amino acid 


46- Name a peptide  hormone which prevents diuresis

( ADH)

47 What is the basis of using raw egg for heavy metal poisoning ?

( Egg protein binds with heavy metal to form metal proteinate complex, which is water-soluble and is excretable, else heavy protein binds with tissue proteins to cause damage)

48- The tertiary structure of a protein describes sequence of amino acids- true or false ?

( False- Tertiary structure describes the folding of the protein )

49- Give two examples of haemoproteins.

(Hemoglobin, Myoglobin, Cytochromes, Catalase, Peroxidase and Tryptophan Pyrrolase)

50-  In a protein the disulphide bridges can be broken by–

 ( Reduction )



Please help "Biochemistry for Medics" by CLICKING ON THE ADVERTISEMENTS above!