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PROTEINS
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PROTEINS

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  • 1. Proteins DEF:- chemically protein is a polypeptide of 30-50 - amino acids, i.e amino – carboseylic acid joined together lay peptide linkage. It is the most impt of all the agonic subs. And no life is possible with out it. Composition:- mainly it is composed of c, N2 , O2, H2 and S. but some proteins contain P, Fe, I2 ,Cu, Mn, Zn ++ . And other elements.
  • 2. Sources:- Aminal :- Egg, Fish, Poultry, Meat, Milk cheese. Plants:- Peas, Nuts. Soya beaus, Potatoes, Storage:The capacity of lining organisms. for storing proteins is limited and relatively small as compased to its capacity for string CHO and Fats. Although many plants and may bacteria are capable of synthesizing protein from simple orgamic and inorganic compels;
  • 3. but this capacity is least in higher animals. Requirement:- 1 gm/ Kg of body mt (double for children) or 46 gm / 70 kg body wt for adults. Functions:1. Catalytic :Most of the enzymes are protein in nature. They catalyse various reactions e.g.. Pepsin, trypsin, clnymo trypsin. 2. Proteins take an essential part in the formation of protoplasm.
  • 4. 3. Proteins are an integral of all viruses which are very imp. From pathogenic point of view. 4. Protective and defensive function. The immunoglobulin form defensive function. 5. Muscle contraction and expansion are in every movt. me make. Muscles are made up of proteins ACTIN and MYOSIN . 6. Transport:- Proteins act as carrier of many subs. e.g.. Hb carry O2 and Co2. serum albumin carry fatty acids; bilirubin. Other proteins carry Fe, Cu, and Vit. A .
  • 5. 7. Structural function:- 3 imp. Structural proteins are:i. Keratin :- which is the chief constituent of hair, skin and nails. ii. Collagen:- in connective tissue. iii. Elastin:- Ligaments contain elastin. 8. Proteins are responsible for maintenare of osmotic pressure. and PH due to colloidal nature.
  • 6. 9. Hormonal function:- Most of the hormones are protein in nature e.g.. Insulin, Growth hormone, parathyroid, adrenocorticotropin hormone (ACTH) . 10.Nutrient and storage function. Some proteins store material like starch. and glycogen store energy e.g casein in milk, ovalbumin in egg. Ferritin in liver store iron.
  • 7. 10.a .a Peptide reside Poly ‘’ > 10 a . a reside Pr . * with md. mt 7 Structure:- NH 2 │ R ─ C ─ COOH Side chain C- │ H + NH3 │ R ─ C ─coo │ H Ionic from
  • 8. Free carboxylic gp. R O H R O │ ││ │ │ ││ H2N ─ C ─ C ─ OH + H N ─ C ─ C ─ OH → │ │ H H Free amino gp. +HO2 R O H R O │ ││ │ │ ││ H2N ─ C ─ C ─ N ─ C ─ C ─ OH → Dipeptide ↓ contain one Peptide linkage. Linkage. l. e
  • 9. O H ││ │ ─ C ─ N─
  • 10. Classification:1. 2. 3. 4. 5. Proteins are classified depending upon:Biological value. Function. Structure. Physicochemical properties. Solubility .(some proteins are hydrophilic and some are hydrophobic ).
  • 11. I BIOLOGICAL NOTRITIONAL VALUES. OR Porteins are divided into 2 gps. i. Complete or first class proteins also called “ high biological valve. proteins”. These are the proteins which contain all the essential amino acids. in their structure. ( essential a.a are those which can not be synthesized in the body but are present in the diet.) e.g casein of milk, fish, meat and egg.
  • 12. ii). Incomplete or 2nd class protein also called “Proteins of low biological value”. These are the proteins which do not have all essential a.a in their structure. Some a.a are missing and they are known as “ limiting amino acids”. e.g “Animal proteins” like gelatin lack tryptophane which is an essential a.a. “Plants” i.e. corn lacks lysine and tryptophane. Rice lacks, Lysine and threonine. Soya lacks, methionine.
  • 13. II CLASSIFICATION DEPENDING UPON FUNCTION:1. Catalytic proteins:- e.g enzymes i.e. trypsin, pepsin, chymotrypsin. etc. 2. Regulatory or hormonal:- e.g Insulin GH , ACTH. 3. Structural proteins:e.g collagen elastin and keratin. 4. Transport protein:- e.g. transferin. (Fe) ceruloplasmin (Cu).
  • 14. 5. Immune proteins:The defensive mech is made by immune proteins e.g ɣ - globulin . 6. Contractile proteins:- e.g Actin and myosin. 7. Genetic:- DNA and RNA both contain proteins in combination with nucleic acid. These proteins are Histones and protamines. 8. Storage:- e.g casein in milk, Gluten in wheat, Zein in maize. Gliadin in wheat.
  • 15. III CLASSIFICATION DEPENDING UPON STRUCTURE:- STRUCTURE:- ( Soluble non structural ) i. Globular proteins:- Also known as “non- structural proteins”. The axial ratio ( i.e. ratio of length to width ) is less than 10 and usually b/w 3-4 molecules of protein is compact and poly peptide chains are coiled e.g. Insulin, plasma albumin , globulin enzyme protein, Hb and Imoglobulin.
  • 16. ii. Fibrous protein or structural protein (Insduble) they have axial ratio greater than 10. the polypeptide chains are coiled in spiral or helical . These are long thread like mol. Whose helical strands form fibers or sheets . e.g. keratin, collagen, myosin and fibrin.
  • 17. DEPENDING UPON PHYSICOCHEMICAL 1). Simple proteins. PROPERTIES:- 2). Conjugated or compd pr. 3). Derived proteins. 1). Simple proteins:On hydrolysis only give a. a or their derivatives and are of 2 types depending upon shape and size of poly peptide claims. i). Globular pr. ii). Fibrous pr.
  • 18. i). Globular proteins:- All enzymes are globular proteins and include a large no. of proteins. e.g. . a). Albumin:- these are soluble in H2O. Sources:- Animal:- Serum album, of egg. Plants:- Legumelin. Properties:1. They are coagulated by heat. 2. Not ppted. by ½ sat. which (NH4) SO4. 3. They form 60% of total pr. And first class pr. Plasma level 4.6 – 6.4 g%
  • 19. b). Globulin:1. Insoluble in H2O and soluble by salt soln. 2. Coagulated by heat. 3. Ppted by ½ sat. with (NH4)2 SO4. plasma level. 1.2-2.3 g%. Sources: Animal :- lactglobulin, myosin in muscle, serum globulin, thyrolgobulin of thyroid gland. Plant-seed
  • 20. C). Protamines:- Present in sperm cells, are rich in argenine. and are basic in nature. Also have tyrosine and tryptophane .In combination with RNA form nucleo pr. d). Histones:- Soluble in H2O. Rich in arginine, basic in nature. Combine which DNA to form nucleoproteins or nucleo Histones. Which are present in cell nuclei and form chromatin material.
  • 21. e). Globins:- Rich in a. a histidine not basic in nature. They combine with haem – which contain from and tetrapyrol sing- to form Hb and myoglobin. Diff . Species of Hb differ only in globin while haem portion is the same. f). Plant proteins are Glutelins e.g. gliadin of wheat and zein of maize.
  • 22. 2. Conjugated or compound proteins:- Proteins combine with non protein part i.e. organic and inorganic that are called prosthetic groops. Prosthetic parts are covalently bound to the proteins and they are necessary for their function if the prosthetic group is removed from the protein then the protein has no function. They are further ÷ed x sub classes acc to their prosthetic gp.
  • 23. Phosphoprotein. 2. Muco protein or glycoprotein. 3. Nucleo protein. 4. Chromo protein. 5. Metalloprotein protein . 6. Lipoprotein. 1. Phospho proteins:- contain phophorous. e.g. casein of milk, ovalbumin. of egg. While some enzymes (e.g. pepsin) are also phosphoprotein protein. 1.
  • 24. 2. Mucoproteins:- They contain CHO or Mucopolysaccharides. The CHO part is attached to serine, asparagines or threonine. They are viscous in nature due to which they act as lubricants and have a protective function. e.g. mucosa in respiratory tract is a glycoprotein and it protects it from bacterial invasion. Gastric and intestinal mucus protects the gastric mucosa from erosive action of HCl. The irritation of gastric
  • 25. Mueasa, hyperacidity or vagal stimulation ↑se mucus secretion. Blood group subs. are also mucoprotein in nature. Cervical mucus protects the uterus against the invasion of microbial flora. 3. Chromoproteins:- These are the compds. of proteins with pigments such as haem and include Hb and cytochromes. Other e.g. are the enzymes e.g. Flavoproteins – contain flavin pigment. Visual –lodopsinpresent in eye visual purple – Rhodopsin – present in eye. The prosthetic gp is carotene (VtA).
  • 26. 4. Nucleoproteins:- contain CHO, H3 PO4 and nitrogenous base (purine and pyrimidine) and pr. DNA and RNA. These 2 nuclear acids are formed by nitrogenous base which may be purine or pyrimidine. Sugar and H3 PO4 complex. They are present in cell nuclei, protoplasm of cell, glandular tissue i.e thymes, pancreas etc.
  • 27. 5. Metalloproteinase:- are the proteins in combination with metals. Metals are necessary for their action. e.g. enzymes alcohol dehydrogenate has Zn as prosthetic group. If Zn is removed. The enzymes will have noactivity. Important enzymes which have metals as their prosthetic group are:Phosphotronsferase Mg Tyrosinase Cu
  • 28. Ceruloplasmin Cu Carbonic an hydrase Zn Arginase Mn 3. Derived Proteins:- They are derived. from simple or compound proteins by various chemical reactions. They are of 2 types:- i). Primary derived proteins. ii). Secondary derived proteins.
  • 29. i). Primary derived proteins:- also called as denatured proteins , in which some or all cross linkages which normally keep the molecular structure intact are broken. Denaturation controls all the functions of proteins e.g. solubility, enzyme activity, specialized role if any. In primary derived proteins primary structure is retained. and esp. zndry and tertiary. structure is disturbed. Denaturation may be reversible or irreversible depending upon the denaturing agents. and the extent of denaturation.
  • 30. Denaturing agents may be physical or chemical such as:- • x- rays, • vigorous shaking heat and light, low pH, salts of heavy metals like PbCl2, HgCl2 denaturation ↓es solubility so the denatured protein is easily coagulated at isoelectric pH. (the pH at which amino acid has no charge). Denaturation of dietry protein is useful: denatured proteins are more easily digestible. Imp . e.g. are – cooked egg albumin . – cooked meat proteins.
  • 31. ii) Secondary derived proteins:Are formed by hydrolysis of simple or conjugated proteins by acid or enz. e.g.proteoses- peptones – polypeptides. And – oligopeptides, acc to their mol.wt. Proteoses:- They are insoluble in H2O – they are not coagulated by heat – they are ppted by ½ and Full sat. with (NH4)2 SO4.
  • 32. Peptones:- They are formed by hydrolysis of proteoses. -They are soluble in H2O. -They are not coagulated by heat. -They are not ppted by”(NH4)2 SO4”but by special ppting agent i.e phosphotungstic acid . Polypeptides:- They are formed by hydrolysis of peptones. The mixture of above is obtained. by
  • 33. digestion of proteins by enzymes. Simple Proteins:- ( c globular proteins) Fibrous Proteins:- They are large mol. and composed of 2 or more poly peptide chains which are coiled around each other. Fibrous pr. are basic structural elements of connective tissne imp. e.g. are:-Collagen:- are present in C.T thorough – out the body. e.g. Skin, bone and tendon. It is resistant to proteolytic. enzymes like “pepsin” and “trypsin.”
  • 34. They are converted to easily digestible soluble proteins like gelatin by boiling with H2O HCl, and alkali. It contains proline, glycine, hydroxyproline. and very small ant of tyrosine. It contains no tryptophane. Elastin:- are extracellular fibrous protein and occur in elastic tissues e.g. “tendons and arteries”. It is not converted to gelatin and has little or no Hydroxy proline the elastic tissue is a
  • 35. mixture of “ elastin”, “collagen” and CHO containg protein called “elasto mucin”. Keratin:- it occurs in animal skin, nails, horns, hoofs, hair, wool, feathers etc, to which it gives strength. Keratin is found with in the cells. It is insoluble. in H2O, organic solvents, and in dil. Acids and alkalies. It has high Cystine content forming cross-links b/w peptide chains which provide. strength to its mol. Chemically keratin is quite inert and resistant.
  • 36. Lipoproteins:Diseases due to lipoproteins. Hyper lipoproteinemia:- It is the clinical finding of high conc of particular class of plasma lipoprotein. They are of 5 types and these are type I ,II ,III ,IV, V. Type I:- are rare disorder in which only chylomicron. fraction is ↑ed abnormally. This type of disorder occurs in patients with genetic deficiency of “lipoprotein lipase” in adipose tissue.
  • 37. Type II:- are ↑ sed β – Lipoproteins. It is due to low density density lipoproteins or both VLDL and LDL. This type of disorder occur both in hereditary form and acquired form. These patients have ↑sed risk of atherosclerosis of coronary arteries and ↑ed amt. of cholesterol. Type III or β Lipoproteinemia:- it is a rare disorder due to presence of abnormal lipoprotein in plasma. It is the hereditary form and sometimes it is due to zndry
  • 38. effect of “hypothyroidism”. These patients show early atherosclerosis and have ↑ed risk of vascular disease. Type IV. or pre –β – Lipoproteinemia:- It is due to ↑sed amt of VLDL. It is hereditary form and is found in patients who are over weight. It is seen in patients who have a tendency towards diabetes M. Type V.:- It is rare and appear zndry to diabetes mellitus pancreatitis. It is characterized ↑ed chylomicron and LDL.
  • 39. Hypolipoproteinemia:- It is a genetically transmitted disease and is due to absence of “ chylomicron.” “LDL” “VLDL” which is due to inability to synthesize “apolipoprotein”pr. Type which combine with lipid part.
  • 40. Properties of Proteins 1. 2. 3. They form colloidal soln. Of “hydrophilic type” They have “amphoteric.” property. They combine both with acid and alkali to form ionizable salts. On hydrolysis give crystalline subs. Of specific composition known as amino acids.
  • 41. 4. For every protein there is a definite characteristic pH. Known as “isoelectric pH”. at which particles are neutral. Also known as “lsotonic point” or “isotonic pH”. All proteins are least soluble at isoelectric pH. But certain proteins like “gelatin” and “ovalbumin” remain in their soln from. 5. Optical activity is due to the presence of asymmetric C- atom and have the
  • 42. property to rotate the plane polarized light. 6. Diff. pr. Have diff. md. wt. depending on this property, diff. pr. Can be separated by a technique known as “ultra centrifugation”. 7. Dialysis:- proteins cant pass through semi permeable memb (like cellophane) depending upon this property dialysis can be used to serarate. Pr. From.
  • 43. Crystalloids which can pass through. 8. “Buffer action.” (resistance to change in pH) Proteins form very good buffer pairs:. They are present in salt form as well as acid form. They can act as buffers on both sides of isoelectric point. “Haemoglobin” is the best buffer in blood. At physiological pH proteins are – -vely charged ions. At isoelectric point the pH is neutral. Na Pr , K. Pr . K. Hb Bld p.H H. Pr H.Pr H.Hb. 7.34-7.43
  • 44. 9. Hydration property:- protein in aq. Media holds certain amt. of H2O due to formation of H- bond b/w H2O and pr. Polar gps. Like NH2, COOH, OH, CONH2 form hydrogen bond.
  • 45. H │ R─ C ─ COOH │ H─ N ─ H amino acid Hydrogen bond. H │ + R─C─CO ─ H ─ │ + H─N─H H │ + H─O H + H O
  • 46. In this way pr. From a shell of H2O oround it. 10. Precipitation of Pr:- It is not a chemical change. There is adsorption of one ion on the other. - Proteins are ppted from soln by salts of heavy metals like HgCl2 AgNO3, CuSO4.
  • 47. - - Pr. Are ppted by certain acids which are called alkaloidal reagents like picric acid, Phosphotungstic acid, tannic acid and H3PO4 in the basic medium. By conc soln of such salts like, (NH4)2 SO4 , Na2 SO4 and Na Cl. Pr. Are also ppted by dehydrating agents like methyl and ethyl alcohol.
  • 48. Mechanism:- By neutralization of charges:- it results in decrease in repulsion. By removal of shells in which H-bond is broken. Proteins form colloidal sol. Of the type called “emulsoid”. The most imp property of emulsoid is that they have 2 stability factors. “Charge and hydration” either of which is capable of keeping the
  • 49. protein md. in soln. individual proteins show marked difference in the hydration of their particles.
  • 50. MECH OF PPTION:+ Ve Pr (emulsoid ) + + ++ acid + + Pr. Care Shell of H2O - ++ Dehydrate ++ - -ve protein -(emulsoid) dehydration + + alkali or + electrdyte + + + + ve Pr. Suspenoid ppt. Acid or Elector lyte Suspenoid -velycharged protein
  • 51. Solubility of pr:- Depends upon distribution of hydrophobic or hydrophilic groups. If more hydrophilic groups are present on the surface then it is more soluble. On the other hand if more hydrophobic groups are present on the surface then it is insoluble. Denaturation :- Protein is called “native protein” if its structure remain unchanged. From the natural state.
  • 52. This property controls all the function of protein. It its structure is changed it is called “denaturation”. It occurs when weak forces which are responsible for secondary, tertiary and quaternary structure are disturbed that results in unfolding and uncoiling of protein molecule. Which is responsible for change in physical and in some chemical properties. It is caused by:-
  • 53. - Heat which causes splitting of salt bridges by thermal agitation . - By vigorous shaking and stirring. - By ultraviolet radiation . - Ultrasonic rays which destroy the ring of aromatic a. a. - By mineral acids and alkalis. Denaturation maybe “reversible” or “irreversible” depending upon the denaturing agents and extent of denaturation. From biological point of view denatured proteins are useful . .
  • 54. they can be digested easily. AMINOACIDS (AA) Amino acids are organic subs. Containing an amino (NH2) and carboxylic gp (COOH) these are basic units of proteins. in nature 300 amino acids are found but only 20-22 aa are involved in protein formation which are - amino acids and these are called stand and primary or normal amino acids.
  • 55. Biomedical Importance of aa. 1. 2. 3. Some a a have highly specific function in the body e.g. citruline or ornithine they are present in liver and they form urea from NH3 G. A. B. A:- Gama amino butyric acid. It is present in brain and other tissues. It acts a neurotransmitter . D O P A :- Dihydroxy phenyl alanine. It is found in tissues during the metabolism of tyrosine and phenylalanine .
  • 56. It is used in the treatment of parkinsonism . 4. Decarboxylation of a a give compounds like Histamine which is a vasodilator. 5. Abnormal transport of a a in cell and excretion in urine give disorder called Amino acid uria. 6. Iodinated a a is useful in synthesis of thyroid hormones T3 – T4 .
  • 57. Structure:Gen . Formula . NH2 │ R ─ C ─ COOH │ H (having both the charges)
  • 58. COOH │ H ─ C ─ NH2 │ R or H - amino acid All natural a a Are - aa COO │ + H ─ C ─ NH3 │ R Hermaphrodite Zwitterions Ampholyte or Dipole
  • 59. All a.a have a symmetric c- atoms. in their structure i.e why they have the property to form . Isomers. L- NH2 gp is on left D. NH2 towards right COOH COOH │ │ NH2─C─ H H─ C─NH2 │ │ CH3 CH3 D (-) alanine levorotatory L (+) alanine dextrorotatory
  • 60. All AA except glycine have isomers and are optically active. The designation of AA to D or L is derived from the compd D and L form of glyceraldehydes NH2 if it is on the right side then it is D NH2 “ “ “ “ “ left “ “ “ “ L D – alanine rotates the plane polarised light towards left and L alanine is dextrorotatory:. It rotates the plane polarised towards right.
  • 61. CLASSIFICATION OF AA:I) Acc to the structure II) “ “ “ Polarity of side cham III) “ “ nutritional valve IV)“ “ Metabolic products formed in the body V) “ “ their affinity for H2O i.e hydrophilic – hydrophobic .
  • 62. Acc . To their structure:They are further ÷ ed x following I. Neutral ─ Aliphatic Aromatic S- containing Heterocyclic 2. Basic 3. Acidic 4. Imino acid I)
  • 63. NEUTRAL AMINO ACIDS:They are monoamine monocarboxylic acid with a side chain which may be aliphatic, aromatic or cyclic Acc to the nature of side chain aa are further ÷ ed x :a. Aliphatic aa b. Aromatic aa c. Sulphur containing aa d. Heterocyclic aa.
  • 64. aliphatic a a :- They have aliphatic side chain which may be straight or branched. e.g. i). Glycine:- Simplest aa and has no a symmetric c – atom. NH2 │ H ─ C ─ COOH │ H a.
  • 65. ii). alanine :- (Ala ; A) NH2 │ CH3─ C ─ COOH │ H
  • 66. iii). Serine :- ( ser ; S) NH2 │ CH2 ─ C ─ COOH │ │ OH H
  • 67. iv). Threonine :- (The; T) NH2 │ CH3 ─ CH ─ C ─ COOH │ │ OH H
  • 68. V). Valine :- (Val ; V) CH3 CH3 H NH2 │ │ C ─ C ─ COOH │ H
  • 69. Vi). Leucine :- (Leu ; L) CH3 CH3 H NH2 │ │ C ─ CH 2 ─ C ─ COOH │ H
  • 70. Vii). Iosleucine :- ( lle ; I) CH3 C2 H5 H NH2 │ │ C ─ C ─ COOH │ H
  • 71. b). Aromatic amino acids :- They have phenyl or hydroxyphenyl ring in their structure. viii). Phenyl alanine:- ( Phe; F) NH2 │ ─ CH2 ─ C ─ COOH │ H
  • 72. ix). Tyrosine :- (Tyr ; Y) HO ─ NH2 │ ─ CH2 ─ C ─ COOH │ H
  • 73. C) Sulphur Containing a a :- They are :x). Cysteine :- (Cys ; C) NH2 │ CH2 ─ C ─ COOH │ │ SH H
  • 74. Tow mol. Of Cysteine are linked through –s –s – linkages forming cystine Cysteine :NH2 NH2 │ │ COOH ─C─CH2 ─S─S─CH2 ─C─COOH │ ↓ │ H H Disulphide linkage.
  • 75. Methionine :- (Met ; M) NH2 │ CH3 ─ S ─ CH2 ─ CH2 ─ C ─ COOH │ H
  • 76. d). Heterocyclic a a :- which have indol in their structure:Tryptophane :- (Try; W ) NH2 │ ─ CH2 ─ C ─ COOH │ N H │ H
  • 77. BASIC AMINO ACIDS:They have more than one amino group in their structure e.g. arginine, histidine, lysine, Asparagine, glutamine. Glut amine O NH2 ││ │ NH2 ─ C ─ CH2 ─ CH2 ─ C ─ COOH │ H
  • 78. ACIDIC AMINO ACID:- They have more than one carboxylic group i.e – COOH e.g. Aspartic acid, glut amic acid. Glut amic acid:NH2 │ HOOC ─ CH2 ─ CH2 ─ C ─ COOH │ H -
  • 79. Imino acid :- They have imino (NH) gp. Instead of (NH2) group in their structure e.g. praline it is a derivative of pyrolidine and is an e.g. of cyclic a.a. In some cases proline is hydroxylated to form Hydroxyproline and usual form is 4Hydroxyproline . Proline 4- Hydroxyproline. HO─ 4 3 - COOH ²─¹COOH - N │ H N │ H
  • 80. - SPECIAL AMINO ACIDS :- They are not imino in protein formation but play very imp. role and have highly specific functions e.g. G A B A – acts. as neurotransmitter D O P A – in t/m of parkinsonism . Iodinated a.a i.e Monoiodotyrosin Diiodotyrosine, tri – iodotyrosine (T3) and tetra iodotyrosine (T4) clinically T3 and T4 are used in finding the disease of thyroid.
  • 81. II). ACCORDING TO POLARITY OF RGROUP AT PH 7.0: amino are again ÷ed x 4 sub- groups:1. Non polar R – group. 2. Polar but uncharged R- group. 3. -Vely charged R- group. 4. +Vely charged R – group. - NON POLAR R – GROUP:e.g. Alanine, leucine, Ioseucine, Methionine , phenylalanine, proline, Tyrosine, Valine.
  • 82. -Polar but uncharged R - Group:e.g. serine, threonine, tryptophane, Cysteine. -Negatively charged R - Group:e.g. Aspartic acid, Glutamic acid. -Positively charged R- Group:+ve charge is due to the presence of an additional group. e.g. Lysine, Arginine, Histidine.
  • 83. iii). Classification Acc. to nutritional value:- Was given by Black in 1956. a.a have been ÷ ed x 3 gps. Essential a.a or indispensible a.a . Non “ “ “ dispensable a.a. Semi “ “ “ Semi indispensable a.a. Essential a.a or indispensible a.a. Are those a.a with are not synthesized in the body by any organic subs.
  • 84. but must be present in the diet. For adults 8. a.a are essential and for children 10 a.a are essential. They are:• Threonine • Tryptophane • valine . • Leucine • Isoleucine • Methionine • Phenylalanine • Lysine • Histidine and • Arginine. (in children ). - Non Essential a . a :- They can be synthesized in the body from other organic amic subs. e.g. Glutamic acid; Aspartic acid,• Asparagines, • Alanine,• Proline, • Hydroxy proline; • Glutamine, • tyrosine, •Cysteine; serine.
  • 85. Semi Essential a.a :- some of them are synthesized in the body, but the amt. is not enough to meet the reqmt. e.g. ; Arginine ; Histidine. iv). Classification acc to metabolic products:- They are again ÷ed x 3 sub gps. a. Ketogenic a.a b. Glucogenic a.a c. Keto and glucogenic a.a. -
  • 86. a. b. c. Ketogenic a.a :- on metabolism give rise to ketone bodies e.g. acc to acetic acids β- Hydroxybutyric acid,• Acetone. Glucogenic a.a :- They give rise to glucose and glycogen or subs. With give these compds. e.g. • Alanine, • Glycine, • Arginine, • Threonine, • Valine, • Methionine, • Cysterin,• Cystine , • Histidine, • Proline, •Hydroxyproline. Keto and glucogenic a.a:- e.g. Isoleucine, Tyrosine, Tryptophane.
  • 87. v).Classification affinity for H2O:- - - Acc to their They are ÷ ed x 2 groups side chain charged at pH6 “ “ un “ “ “ “ Side chain charged at pH6 are called Hydrophilic .e.g. •Lysine, • Arginine, • Histidine, • Asparginine, • glutamic acid. Side chain uncharged at pH6.
  • 88. Hydrophobic Alanine Valine Leucine Isoleucine Proline Phenylalanine Tryptophane. Hydrophilic Glycine Serine Asparginine Glut amine Cystine Threonine Methionine
  • 89. Properties of amino acids physical properties:1. 2. 3. These are white crystalline subs. Crystalline forms are sp. for a.a. Solubility :- they are soluble in H2O acids and alkalis. Melting point:- Diff .a.a have diff, melting points . And decompose at or near its melting point. They have high melting point so large amt. of energy is required to disturb the forces of its crystalline structure
  • 90. 4. Optical activity:- all amino acids except glycine possess at least one a symetric C- atom in their structure and the no of possible stereoisomer will : be at least 2. the configuration of amino group- NH2 around the asymmetric C – atom is used as reference just as the configuration of OH around the asymmetric c – atom of glyceraldehydes is used reference for sugars.
  • 91. COOH COOH │ │ NH2 ─ *C ─ H H ─ *C ─ NH2 │ │ H ─C─H H─C─H │ │ OH OH L – Serine D – Serine * Asymmetric C – atom
  • 92. 5. Taste :- some a.a are sweet in taste like glycine and alanine. Some are tasteless like Leucine. Some are bitter in taste e.g. Isoleucine and Arginine.
  • 93. Chemical properties:Acid / properties of amino acids:Amino acids in aq. Soln contain weakly acidic α - carboxylic groups and weakly basic α- amino groups. In addition, each of the acidic and basic amino acids contains an ionizable group in its side chain. This both free amino acids and some amino acids combined in peptide Linkages can potentially act as buffers.
  • 94. A buffer is a soln which resists any change in pH when an acid or a base is added to it. A buffer is made by equal amts. Of weak acid and its conjugate base. The quantitative relationship b/w the [ ] of weak acid (HA) and its conjugate base (A) is determined by handerson hasselbalch equation i.e. pH = pKa + Log base acid
  • 95. Titration curve of acetic acid:The Handerson- Hasselbalch equation can be used to calculate the pH of a soln containing a weak acid after the addition of strong acid or base. OH HO 2 CH3 COOH I Aceticacid ,HA CH3 COO H+ II acetate , A
  • 96. If acid is added CH3COO can neutralize and if base is added then CH3COOH can neutralize and dissociate into CH3 COO and OH to form H2O. Thus a soln containing acid and base with a . pKa 4.8 resist resist a change in the PH from 3.85.8 with max. Buffering at pH 4.8 which is pka. A conjugate acid/ base pair can serve as an effective buffer when the pH of a soln is with in approximately + 1 pH amt of the pKa of the weak acid.
  • 97. Whereas max. Buffering capacity occurs at a pH equal to the pKa. At pH values less than the pKa the protonated acid form is predominant. At pH values >er than the pKa the deprotonated form is predominated.
  • 98. Eq. of OH- added Buffer region 1.0 [ II ] > [ I ] [ I ]-[II] [ I ] >II 0.5 pka = 4.8 0 0 3 4 5 6 7 pH Titration cure of acetic acid
  • 99. Titration of alanine 1. Dissociation of the carboxyl group:- alanine contains both a carboxyl and NH2 gp. At a low or acidic pH both of these groups are protonated. As the pH of the soln is raised the – COOH group of form I can dissociate; by donating a proton to the medium and results in the formation of the carboxylate gp; - COO . Which is the dipolar form of the mol. also called Z witterions with no charge and is the isoelectric form of alanine with an over all charge of zero.
  • 100. Handerson Hassalbalch equation is used to analyze dissociation of – COOH gp. So pH = PK, + log II I 2. Dissociation of NH2 gp:NH3 is a much weaker acid – than – COOH gp. Release of proton from the protonated amino gp. form II results in the fully deprotonated form of alanine i.e form III. +
  • 101. This sequential dissociation of COOH and NH3 from alanine is shown below:H OH H2O H OH H2O H │ │ │ H3N ─C ─COOH → + │ CH3 - H3N ─C─COO → ← H+ PK1 = 2.3 ↓ I Fully protonated pH less than 2 │ CH3 ← H + Pk2=9.1 ↓ II Isoelectric pH6. net charge 0 - H2N─C─ COO │ CH3 ↓ III pH 7er .10 Net charge-1
  • 102. Each of the titrable gps has a pKa i.e numerically equal to the pH at which exactly ½ of the protons have been removed from that group. The pka for most acidic group (- COOH) is pK1 . Pka + for the next most acidic gp (-NH3 ) is pk2.
  • 103. Titration curve of alanine:The titration curve shows the pH changes during the addition of base to the fully protonated form of alanine (I) to produce the completely deprotonated form (III) the – COOH /- COO pair can serve as a buffer in the pH region around pK1 and the – NH3/ - NH2 pair can buffer in the region around pk2.
  • 104. Region of buffering → ← region of buffering Equivalents Of OH added [I ] = [III] 2.0 PI=5.7 1.5 pk2 = 9.1 [ I ] = [ II] 1.0 Pk1 = 2.3 0.5 0 2 4 6 8 10 pH When pH = pK1 (2.3) equal amts of forms I + II of alanine exist in the soln and when pH = pK2 equal amts of II and III exist in the soln .
  • 105. Isoelectric point :- At neutral pH, alanine exists predominantly as the dipolar form II in which the amino and carboxyl gps are ionized but the net charge is zero Isoelectric point is the pH at which an amino acid is electrically neutral i.e where the sum of the +ve charges equals the sum of the -ve charges . For a. a like alanine which has only 2 dissociable hydrogen's the PI is average of pk 1, and pk2 i.e pl = 2.3 + 9.1 = 11. 4 = 5.7 2
  • 106. This value is midway b/w pk1. and pk2 it corresponds to pH where structure ll predominates and at which there are also equal amounts of form 1 and III. At physiologic pH all a.a have both – ve and + ve charged gps. And are dipolar, ions . So they act as acid and base and are known as ampholytes or amphoteric electrolytes.
  • 107. Titration of Histidine :- Histidine contains 3 chemical gps. eash of which can reversibly gain or lose a proton; the COOH gp -NH2 gp and the imidazole gp.
  • 108. H │ + H3N ─C─COOH │ CH2 │ HO H │ + H2O H3N─C─COO │ CH 2 │ HN H2O H+ C = CH + OH │ NH // C │ PK1 = 1.8 H │ Net charge = +2 H+ │ C = CH │ │ +HN NH // C ││ PK2=6.0 Net charge =+1 H │ + H3N─C─COO │ CH 2 │ C= CH │ │ N NH / C │ H │││ Net charge= 0 (isoelectric for)
  • 109. OH H2O H+ PK3=9.2 H │ H2N ─C─COO │ CH2 │ C = CH │ │ N NH // C │ H Net charge = - 1
  • 110. the addition of bore fully Prorogated his result in removal of COOH proton pk1=1.8.the inidazole gp pk2= 6 and nh2 gps 9.2 the I P can be calculated by indentifying zwitterion. Then average . So . x. . PI = pk2 + pk3 = 6+9.2 = 15.2 = 7.6 2 2.
  • 111. 2). Formation of peptide linkage or bond:The amino acids are attached to their neighboring acids by- COOH gp on one side and by NH2 gp on the other with elimination of one H2O mol. In this way an acid amide bond is formed which is called a peptide bond.
  • 112. The general formula of peptide b/w 4 a.a residue forming a tetra peptide is: R O H O H R O H R │ ││ │ ││ │ │ ││ │ │ H2N ─ C ─ C ─ N ─C ─ N─ C ─C─ N─ C─COOH │ │ │ H H H Side containg free side containg amino gp free carboxyl gp. O H ││ │ The bond ─ C ─ N ─ is the peptide bond and in the above formula there are 3 such bond joining 4 a.a and a tetra peptide is formed.
  • 113. Peptide of more than 10 a.a. are called polypeptides. Following reactions are used for detection and measurement of a.a. Ninhydrin reaction :- All a.a having one free NH2 and COOH gp give purple or blue gp on treating with Ninhydrin. Reaction with 1 Floro, 2-4 dinitro benzene:- dinitrophenyl derivatives are formed when a.a are treated with reagent.
  • 114. Properties due to COOH group :1. Formation of esters:- Esters are formed when a.a. are treated with Alfold in the presence of H Cl. 2. Decarboxylation reaction:- when a.a is treated in presence of Ba (OH). CO2 evolved in preside of decarboxylase in body. Histidine CO2 Histamine decarboxylase (Vasodilator) .
  • 115. Properties due to NH2 group:1. Acetylation:- when a. a are treated with acetylating agents like CH3 COOH or the amped which provide acetyl gp acetylation takes plare COOH. COOH O COOH O │ ││ │ ││ R─C─ NH2+CH3 ─C─ OH→R─C─ NH─C─CH+H2O │ │ H acetic acid H acetylated acid a.a
  • 116. Addition of acetyl gp to the amino gp is called acetion . 2. Methylation:- when a.a. is treated with mettugl codide in alkaline soln. the product formed is called bution and this property is used for separation of a.a. 3. Reaction with Nitrous acid (HNO2):- is used for determination of free amino gp in a soln. in this reaction nitrogen is evolved and Hydroxy acid is formed. a.a. + HNO2 oxidizing N2 Hydroxy acid.
  • 117. 4. Reaction with. Form aldehyde:(HCHO)- COOH gp is easily titrated against alkali in proenice of NH2 gp.1. This amino gp is blocked by adding formaldehyde. Then this COOH gp is titrated against alkali this method is called formyl litration method and is used for determination of a.a. N2 in ursine.
  • 118. 5. Colour Reactions:- are used for identification and determination of various a.a. chemical reagents are used as sprays to develop chromatograph chromatography is a technique for separation and identifying defferent a.a. 1. Ninhydrin reaction:- It is used for quantitative estimation of a.a. urine and other biological fluids. 2. Biuret reaction :- It forms the basis of
  • 119. quantitative and qualitative estimation of proteins in blood and other finds spectrophoto metrically. When urea is treated at 18 ᵒC it gives a compd. Called buried when biuret is heated with Co So4 and a strong alkali it gives a violet colour so any compd. When has 2 mol. Of CO NH2, CH2 NH2) C (NH) NH2 in its structure it gives this test +ve. At least 2 or more than 2 peptide linkages should be present for +ve result of this test.
  • 120. So its a general test for pr. Or a.a. 3. Xanthoprotein test:- is specific for a.a. honing phenyl alamine. i). p Tryptophane and tyrosine. 4. Modified Millous test:- specific for tyrosine due to presence of phenyl gp. 5. Nitroprusside test:- specific for a.a. having S-M gp. 6. Sulphur test:- is +ve for a.a. containg sulphur in in their stencture receipt methionine.
  • 121. Functions of amino acids:To maintain nutrition. 2. To maintain growth. 3. For life span. CLINICAL SIGNIFICANCE OF AMINO ACIDS:Many a.a. leave and enter the plasma during normal metabolic processes a few remain intracellular circulating a.a. 1.
  • 122. are fittered at the glomerulus and are largely reabsorbed in the tubule by active transport and some a.a. are not fully reabsorbed and appear in urine. Diff a.a. are present in diff. [ ] . e.g. glycive, histidive, alanine, serine – 1 mg /kg. others < 1 or 0.5 mg/kg e.g. tyrosine valine, Levine, threonine. Total amt. of a.a. N2 = 100-200mg/day -300 mg/day. Excretion of >er amts . Of a.a. urine is called amino acid uria. And
  • 123. is of 2 Types:1. Overflow amino acid uria. 2. Renal amino acid uria. 1). Overflow a.a. uria:- There is some sctrarenal metabolic defect as a result of which there is some ↑se in plasma a.a. of one or more a.a. which exceed the capacity of normal renal tubule to reabsorb them. Causes:- i).Severe liver disease. ii). Tissne masting condition like typhoid.
  • 124. iii). Alkalosis. iv). Phenyl ketomria. V). Maple syrup urine disease. 2. Renal a.a. uria :- In this plasma level of a.a. is normal but • • of some failure of reabsorption an ↑se amts of one or several. .a.a. are excreted in urine couses:- i). Defect in single transport mach. ii). Generalized tubloular damage
  • 125. Structure of proteins:Proteins have 4 types of structures:1. Primary. 2. Secondary. 3. Tertiary. 4. Onaternary. 1. Primary structure:- The sequence of a.a. in a protein is called the primary structure of pr.
  • 126. many genetic disease result due to abnormal a.a. sequences. If the primary structures of the normal and the mutated proteins are known, this information may be used to diagnosed or study the disease. Every protein and polypeptide chain structure in biological organism has diff. sequence of a.a. that all oms the protein to carry out function. There are 20 a.a. which enter into the formation of peptide molecules hence x the synthesis of protein molecules.
  • 127. An unlimited no of peptide mol. Are possible from 20 a.a. the no. of a.a. in a peptide mol. Varies from a few to several hundreds or more. Each protein has its own specific sequence of a.a. for e.g. Abnormal Hb which is HbS differ from normal Hb in one respect i.e glutamic acid. is replaced by valine at position no.6 in HbS in β – chain. The primary structure of proteins is regmlated by the respective genes or
  • 128. specific chromosomes. The numbering of a.a. residues in a peptide chain starts from the a.a. containg free- NH2 group. So , In Hb - chain has 141 a.a. β – chain has 146 a.a. The charge in protein properties depends upon the kind of chain. Ribonucleases (enzyme) contains protein chain of 124 a.a. Carboxypeptidase removes one terminal a.a. remaining mol. Has same biological
  • 129. function. Same is the case with diff. insulins from diff. sources. Insulin of cattle or from Hog or sheep differ only in position 8,9 and 10 of A chain and C terminal of porition 30 of β chain. A chain = 20 + 1 21 a.a A chain = 30 a.a. A chain β chain 8 – 9 10 30 Human = Thr – ser – lle The Hog = Thr – ser – Ile Ala Sheep = Atre – Gly – Val Ala
  • 130. The primary structure of human Insulin – ginners as s s ↑ 10 7 11 20 21 A chain a.a. residue s -s ↑ 7 - s-s 19 21 β chain The insulin mol. Consists of 2 peptide chains A+B containing 21 and 30 a.a. residue. These 2 chains are joined to other at 2 sites though interchange – s – s – linkages of Cysteine
  • 131. residues chain A has an interchange – s – s – linkage b/w 2 Cysteine residues present it No. 6 and 11 position. The beef and sheep insulins differ form human insulin to 3 and 4 a.a. respectively. Despite of the light difference, all linear insulin can be used in human and perform save function as human insulin, but some times a slight change in a.a. sequence make a great deal of difference. For e.g. two hormones elution and vasopressin have
  • 132. identical structure at position 3 and 8 but diff. biological activity. The primary structure is regulated by specific gene in specific chromosomes. SECONDARY STRUCTURE:In this structure proteins can fold or align themselves such a manuer that certain patteen repeat themselves – these repeating pattervs are called secondary structure. Important secondary structures absaued are.
  • 133. 1. 2. 3. - Helix Pleated sheet or β ─ structure. Random coil in some protein. - Helix:- is the most common and a spiral structure, consisting of a tightly packed, coiled polypeptide bark bone core with the side chains of the component a.a. extending outward from the control axis. Keratins are a funnily of closely related fibrous proteins, whose structure is nearly entirely -
  • 134. Helical. They are a major component of hair and skin, their rigidity is determined by the no. of disulfide bonds b/w constituent polypeptide chain. On the other hand Hb. Is approximately 80% - helical is a globular, flexible molecule helix stabilised by rctensine H- bonding b/w peptide bond carbonyl oxygen's and amide hydrogen. Each peptide bond participates in H – bonding. Each turn of an - helix contains 3.6 a.a. A helix
  • 135. may be right handed or left handed. A right handed helix is more stable than the left handed. Certain a.a. in protein which may interfere with formation of certain structure e.g. glycme and prolie these 2 a.a. present the formation of - helix. β ─ SHEET OR PLEATED SHEET:It is a form of 2ndry structure in which all the peptide bond components are involved in H – bonding. The surfaces of β - sheets appear “pleated” and these
  • 136. structures are .: often called “ β ─ planted sheets.” β ─ sheets are composed of 2 or peptide chains ( β ─ strands). Or segments of polypeptide chains that are almost fully extended . In β ─ sheets the H- bonds are perpendicular to the polypeptide back bone.
  • 137. ─ R ─ C─H H─C │ │ C N / O─ ─ ─ H O H │ // N C │ │ H ─ C ─R R ─ C ─H │ │ // C ─ H - - - - - - - O N │ │ C H Hydrogen bond b/w chains
  • 138. A β - sheet can be formed from 2 or more separate polypeptide chains. That are averaged either parallel or anti parallel to each other. The band are teemed inter chain bonds when formed b/w separate polypeptide chains. A β ─ sheet can also be formed by a single polypeptide chain folding bark an itself. In this case the H – bonds are intea chain bonds e.g. are the globular proteins.
  • 139. C – Terminal N – terminal N terminal Anti parallel β ─ pleated sheet. C – terminal
  • 140. so β sheet are formed in fibrous and proteins A no- of disease results in deposition of fibrous protein for e.g. ALZHEIMER’S disease. Which results from deposition of amyloidal protein in the brain tissue. β ─ bends are generally composed of 4 a. a. one of which may be praline . G lysine is also fond. Β bends reverse the direction of a polypeptide chain this forming a globular structure. Approximately one 1 of an average 2
  • 141. Globular protein is organized x repetetive str. Such as - helix or β – sheet. The non repepetetive 2mdry str. Are not random and the random coil refers to the disordered structure obtained when proteins are denatured. Globular proteins are constructed by combing 2mdry str. Elements. i.e helixes, β – sheet, non repetetive sequence. And from the core region.
  • 142. Tertiary structure of globular proteins. The primary structure of a polypeptide chain determines is tertiary. The structure of globular proteins in aqueous soln is compost with a high density of atoms in the core of the mol. Hydrophobic side chains are buried in the centre and hydrophobic groups are on the surface of the mol. And are imbed in H – bonds. Tertiary st. is a combination of - Helices and β- strands
  • 143. Domains:- are fundamental functional and 3 duneirsion al structural imts of a polypeptide. Each domain has the characteristic of a small, compost globular protein i.e structurally in dependent of other domains in the poly peptide chain. Interactions stabilising tertiary structure:3 Dimensional structure of each polypeptide is determined by it’s a. a. sequence.
  • 144. 1. 4 types of interaction cooperate in stabinlioing the tertiary structure of globular protein. Disulfide bonds:- A disulfide bond is a covalent linkage formed from the sulfhydnyl gp. (- SH) of each of 2 Cysteine residue to produce a Cysteine residue. The 2 Cysteines may be separated by many a . a. in the polypeptide. Or may be located on 2 diff polypeptide. The folding of the
  • 145. polypeptide can bring the 2 Cysteine residue = in proximity and permit covalent bonding of their side chains.
  • 146. H O │ ││ N―C―C │ │ H CH2 2 Cysteine │ polypeptide Residue SH back bone. SH │ H CH2 │ │
  • 147. N―C―C │ ‖ H O ↓ oxidant for e.g. O2 H O │ ‖ N―C―C │ │ H CH2 │
  • 148. S │ ← Disulfide bond. S │ H ― CH2 │ │ N―C │ H Cysteine residue.
  • 149. 2. Hydrophobic interactions:- Amino acids with non polar side chains tend to be located in the interior of polypeptide mol. Where they associate with other hydrophobic a. a. amino acids with polar or charged side chains Thad to be located on the surface of the mol. In contract with polar solvent. 3. Hydrogen bonds:- A. A side chains containing O2 or N2 – bond hydrogen, such as in alcohol gp. Of serine and
  • 150. threonine can form H – bonds with election rash atoms, such as the O2-gp of carboxyl gp or carbonyl gp of peptide bonds . 4. Ionic interactions:- Negatively charged gps such as carboxyl gp in the side chain of aspartate or glutamate can interact with the tuely charged gps. Such + as NH3 gp in the side chain of lysine.
  • 151. glutamate H H O │ │ │ N―C―C │ CH2 │ CH2 │ C aspartate. H H O │ │ │ N―C―C │ CH2 │ C / O O
  • 152. ≡ H │ H – Bond. O │ H CH2 │ │ ―C―C │ ‖ H Serine H O ≡ NH3 chain bond │ CH2 │ CH2 │ CH2 │ CH2 lysine │ N ― CH2 ― C = O
  • 153. QUARTERNARY ST.OF Hb.    Hb. Tetramer is composed of 2 identical dimes i.e (β )1 and (β )2. 2 polypeptide chains with in each dimer are held to gather primoily by hydrophobic interactions. Inter chains hydrophobic interactions form strong ass. b/w + β sub imts in the divers. I one and H- bonds also occur b/w the members of the dimmers.
  • 154. In contrast the 2 dimmers are able to many with respect to each other, being help to gather primarily by polar bonds.  Weaker interactions b/w these mobile dimers results in the 2 dimers occupying diff. relative position in deoxy Hb compared to oxy Hb. R – Form:- The binding of O2 to Hb courses rupture of some of the conic bonds and H – bonds b/w the β
  • 155. dimmers, leading to st called relaxed or “R” Form in which polypeptide chains have more freedom of in out and Rform has more affinity for O2. T- FORM:- is the deoxy form of Hb. Also known as “T” or taut form. The 2 β , dimers interact through a network of ionic bonds and H – bonds that conation the mout. of polypeptide chains. “T” form is the low o – affinity form of Hb.
  • 156. Quaternary structure of proteins:This structure is shown by there which are made up of more one peptide chain subunits each of which has its own primary, zndry , tertiary st.e.g. Hb it contains 4 chains . 2 chains with 141 a. a and 2 β chains with 146 a. a. these - β chains enfold a harem gp. Which is now in st. the may these 4 subunits polymerize to form is called quaternary
  • 157. structure . It determines now diff submits fit x an orgamied mamer. Globin is a protein of Hb and each globin chain sareand a harem unit is called the prosthetic gp. Similarly pycnic dehydes grease ( enzyme) is formed by assembly of 3 subunits.
  • 158. COLLAGEN. It’s a mall characterised fibrous protein honing structure function in the body's is the most abundant protein in the human body. Collagen be dispersed as get that serves to stiffer the structure as in the extra cellular matrix or the vitreous humane of the eye. In other tissues it may be bundled in tight parallel fibers that provide great strength as in tendons.
  • 159. In bone . In occurs as fibers arranged at an angle to each other in order to resist mechanical sheer from any direction. The polypeptide precursors of the collagen mol. Are formed in the fibroblasts and secreted x the extracellular matrix. After enzyme modification the mature collagen monomers aggregate and become crosslinked to form collagen fibers.
  • 160. Structure of collagen:Types of collagen:- collagen mol. Consists of 3 polypeptides called chains which nrap aramd each other in a triple helix, founding a rope like structure. The 3 polypeptide chains are held together by H – bonds Collagen - chain . b). Amino acid sequence :the primary structure of collagen is a)
  • 161. un usual in that glycine the smallest a. a is frond is every zcd position of the polypeptide chain. Glycine is a part of repeating sequence – Gly – x – Y. where x is praline and is hydroxyproline . c). Triple helical structure :- collagen has an elongated triple helical st. placing may of its side chains on the outside of the mol.
  • 162. d). Hydroxyproline. and hydroxylyoine one important in stabling triple helix st. e). Glycosylation:- The hydroxyl gp of hydroxylyoine of residues of collagen may be hydroxylated.
  • 163. Biosynthesis of collagen:Takes place nudes the following headings:1. Formation of pro - chain. 2. Hydroxylation. 3. Glycosylation. 4. Assembly and secretion. 5. Extracellular cleange of pro collagen mol. 6. Formation of collagen fibrils. 7. Crors link formation.
  • 164. 1.Formation of pro - chain:- Functions outside of cells. Like most proteins synthesised for report collagen contain a special a. a at the N- terminal of their polypeptide chain. This acts as a “signal” that the polypeptide being synttsred is destined to leaue the cell. The signal facilitates the binding of ribosomes to the R E S . And directing the passage of the polypeptide chain x
  • 165. the cistervae of R E R . And field a precursor of collagen called a prochain. 2. Hydroxylation:- The pro- chain are pro- cessed by a no . Of enzyme steps with in the lumen of RER. While polypeptides are still bring synthesised. Selected proline and lysine residues one hydroxylated, found in Y position of the – Gly – x – Y - , to hydroxyproline and hydroxylyoine residues.
  • 166. Redniong agents like vit . C and mol. O2 is required in the reaction. With out which the prolyl hydroxylase and hysyl hydrooxylase are mable function. In the case of ascorbic deficiency collagen fibers can’t be cross linked greatly ↓ing the tensile strength of assembled fiber. Resulting. in disease called SCURVY. 3. Glycosylation:some of the hydroxylase residues are modified by glycolylation with glucose or glucosylgalactase.
  • 167. 4. Assembly and secretion:- after hydroxylation and glycosylation, pro -chain form pro collagen a precurson of collagen that has a central region of triple helix honked by the non helical amino and carboxyl terminal retension called pro peptides. The formation of pro collagen begins with formation of inter chain disulfide bonds b/w the C- terminal extension of the pro - chain. This brings the 3 chains x an alignment for
  • 168. helix formation the pro collagen are trouslocated to the Golgi app. Where they are packed in secret ory vesicles. The vesicles fuse with cell membrane cansing a release of the pro- collagen mol. X the extracellular space. 5. Extracellular cleavage of procollagen molecule:The pro collagen mol. Secreted into the extracellular space is cleaned by N and C pro collagen peptidases. Which remones the terminal
  • 169. peptidase releasing the triple helix collagen mol. 6. Formation of collagen fibrils:Individual collagen mol. Spontaneously associate to form fibrils and subsequent cross linking . 7. Cross link formation:- The fibrillar array of collagen mol. Series as a substrate for hysyloxidase which oxidatinely denominates some of the lysyl and hydroxylysyl residues in collagen.
  • 170. The reactive aldelydes that result can condense with lysyl or hydroxylysyl residues in neighboring collagen mol. To for covalent cross – links. DEGRABATION OF COLLAGEN:- in the extracellular matrix is accompalished by a family of collagenases. That cleave intact collagen fibers x small fagments that can be phagocytosed and further degraded by lysosomal enzymes to their
  • 171. constituent a. a. COLLAGEN DISESES:- Defect in any step in synthesis can result in genetic disease involving an in ability of collagen to from fibers with needed tensile sliengtes. For e.g. “EHLERS- DANLOS Syndrome” in it the skin is stretchy and joints are loose.
  • 172. Osteogenic in perfecta:- also known as brittle bone disease or syndrome bonds can be easily bond or factual resulting in retarded mind heading, tinted spice and humpback appearance.
  • 173. PLASMA PROTEINS GENERAL CONSIDERATIONS:RBC - Blood consists of i). Solid elements WBC ii). Liquid wedum Platelets i.e plasma - Once the blood has coagulated the remaining liquid phase i.e serum lacks the clothing factors including fibrinogen . - Serum does contain some degradation produets of clothing factors.
  • 174. - Determination of [ ] various plasma proteins has a diagnostic value.
  • 175. Basic functions of blood.     Respiration i.e from lung to tissues and CO2 from tissne to lungs. Nutrition transport. Excretion transport. Maintenance of N acid base balance in the
  • 176.      Regulation of H2O balance. “ “ body heat or temperature. Transport of hormones . “ “ Metabolites. Coagulation.
  • 177. Basic characteristics of Pl. proteins    Site of synthesis:- liver, plasma cells i.e ɣ. end otherlial cells. Mostly plasma proteins are glycoproteins •• of N or O linked oligosaccharide chain. Albumin is not a glycoproteins. Haif hife is specific for specific plasma protein Albumin and hepatoglobulin have. 20 days and 5 days in N. adults.
  • 178.   “A cute phase proteins”, also known as reactants and their level ↑es during certain inflammatory reactions and Creactine proteins, - antitrypsin, hepato globin, - 1 acid glycoprotein and fibeniogen their level may ↑se to 50% - 1000 – fold and levels are also ↑sed in chronic inflammations and cancer. - 1 antitrypsin can neutralise certain proteases released during the acute inflammatory phase.
  • 179. Functions of plasma proteins:functions plasma proteins.  Antiproteases  Blood clothing  Enzymes Anticlrymotrypsin 1- Antitrypsin 2 – Macroglobulin Antittrombin various coagulation factory fibrinogen. coagulation factors
  • 180.      cholinesterase aminotransferases. Hormones Erythropoietin. Iumme defense Imno globulins, complement proteins, β -2 u- globulins Inflammatory Resp. CRP. Oncofetal 1- fetoprotein. Transport pr. Albumin, steroids, cemlo-plasma,
  • 181. corticosteroid binding globulin, hepatoglobin lipopr., Rented binding , Thyroid birding globulins transfers in.
  • 182. 1. Albumin.      Mol. Mt is 69 KDA. Makes 60% of total plasma protein- 3.44.7g/dl. Produced in the liver. 12 g/day Albumin is initially synthesised as a prepr. Its synthesis is ↓ed in various liner disease .
  • 183.      A : G is ↓ed in liver diseases. Mahumtrition – kwashiorkor- ↓ed synthesis Consists of one polypeptide chain 585 a.a • • of its lomer mol. Mt and ↑ [ ] it is thought to be responsible for 75-80% of the osmotic pressure of humor plasma. Anolbumiemia – lack of albumin with moderate edema.
  • 184.  Albumin as transporting / binding protein FFA, Ca, certain steroid hormones bilirnbin, Cu , dings e.g. sulfonamides penicillin G, Aspirin etc.
  • 185. 2. Hapto Globin.    Plasma glycoprotein that binds sctrcorpuscular Hb in a tight non covalent complex. Approximately 10 % of Hb that is degraded each day is released X the circulation and is this sctracorpnscular. Free Hb parses through the glomerulus of the kidney, enters the tubules and tendon to ppt. therein.
  • 186.  however the Hb- HP complex is too large to pan through the glomerulus. The function of Hb this appears to be to present low of free Hb X the kidney. This consumes Fe present in the Hb.
  • 187. 3. Transferrin.   It’s a glycol pr. Synthesized in liver is a β 1 – globulin with a mol. Mons of app. 76 K Da. 3+ It transports one iron atom as Fe, mo no ferric form or 2 iron atoms as Fe 3+di , ferric form premed of transferrin in the O to sites where iron is reqd. e.g. from the gnt to the bone marrow and other organs.
  • 188. 4. Ceruloplasmin.   Mol. Mars 160 K D a – an 2- globulin, 90% Cu is carried by it in the plasma. And has a blue colour • • of its high Cucontent Each mol. Of cernls plasmin binds 6 atoms of Cu very tightly, so that the Cu. Is not readily exchangeable. Album carries the other 10% of the plasma Cu but binds the metal lers tightly than does
  • 189.   cernloplasim . Carlo plasim rchibits a Cu- depamadant oxidase activity, but its physiologic significance has not been clarified. The amt. of cernlo plasim is ↓ed in liner disease.
  • 190. 5. 1- Antitrypsin( proteases)    I Amti It inhibits trypsin, elestsise and certain other proteases by forming complexes with their. A deficiency of this protein has a role in certain cases of emphysema. When the amt. Of 1- antitrypsin is deficient and poly mrerphomvclear WBC ↑se in the lung e.g. in pneumonia the affected in dirndl lacks a comter check to proteolytic damage of the lung by
  • 191.   Proteases smh as elastase . Active elastase + 1- AT → inactive elastase : 1- AT complex → no proteolysis of lung → no tusue damage. Active elastase + ↓ or no 1- AT → active elastase → proteolysis of lung → tusue damage.
  • 192. 6. Immunoglobulins  The plasma cells derived from B cells synthesize circulating immunoglobulins called antibodies. Plasma cells are specialsied cells of B lineage that synthesize and secrete immunoglobulins X. the plasma in response to exposure to uaricty of antigens / Immunogen.
  • 193. St. of lmmunoglobulins.    Am immunoglobulin mol. Consists of 2 identical light chains (L) and 2 heavy (H) chains and are linked together via disulfide linked. Each chain can be ÷ed X 2 sp. Domains or regions having specific st. and function. Each light chain consists of a variable (VL) and a constant (CL) region.
  • 194.    and is towards carboxyl terminal. Where as amino terminal half is variable region of the light chain. Each heavy chain consists of a variable region (VH) and a constant region i.e ÷ed x 3 domains i.e CH1, CH2. CH3. VH is ¼ of the heavy (H) chain while the other ¾ of heavy chain are ÷ed x regions i.e CH1, CH2, CH3. CH2 domain contains the complement – binding site and CH3 domain contains a
  • 195. a site that attaches to receptors on nentroplils and macrophages.  Antigen anti body binding site formed by hyper variable region of both the light heavy chains.  immunoglobulin mol. is Y – shaped and chains are linked by disulfide bonds.  Each immunoglobulin has 2 antigen binding figments, (FAB) and one ceystallizable fagmant (Fc).
  • 196.   The site on the antigen to which an anti body binds is temed as epitope or antigenic detriment. The region b/w CH1 and CH2 – hinge region .
  • 197. S ┘ S │ S ┘ ▐ sCO O H S │ -s- S ┌ -s-sS -s-s│ ▐ ▐ S / └ CHO ┌ region S │ S └ COOH COOH ▐▐ │ Variable site with Hypemainable Region Hinge region Complement Binding region STRUCTURE OF IMMUNOGLOBULIN Constant region Of heavy chain │ S he av y NH cha in 2 ┐ ┐ g bin NH 2 om ▐▐ │▐ │ Crystallizable Fragment FC yc H. Ch ai n d bo ti . An tes Si 8 10
  • 198. Ig. Major Functions.    Ig G :- main anti body in zndry response. Makes bacteria easier for phagocytosis x killing and neutralizes bacterial taxis and vines . Crosses the placenta. Ig A :- secretary Ig A perverts attachment of bacteria and vises to mucous membranes. Ig M:- produced in prmiay response to an antigun faces complement.
  • 199. 7.      2 Macroglobulin Large plasma glycoprotein. Homo tetramer. Zn transporting function. Synthesized by monocytes, hepatscytes and astrocyes. Anti protease action,