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Metabolism of amino acids
The document discusses the metabolism of amino acids, carbohydrates, lipids, and proteins, emphasizing their roles as energy sources and in protein synthesis. It details the digestion and absorption processes, the nitrogen balance in the body, the synthesis of various amino acids, and the pathways for protein degradation. Additionally, it covers the fates of amino acid catabolism and the importance of nitrogen excretion primarily as urea.
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Metabolism of amino acids
- 1. R. C. Gupta Professorand Head Department of Biochemistry National Institute of Medical Sciences Jaipur, India Metabolism of Amino Acids
- 2. Carbohydrates, lipids andproteins are energy-giving nutrients Hence they are known as proximate principles of diet Carbohydrates and lipids are used mainly as energy source EMB-RCG
- 3. EMB-RCG Provision of energyis not the primary purpose of amino acid metabolism Amino acids are used mainly to: Synthesize various proteins Form some specialized non-protein products
- 4. EMB-RCG Amino acids canbe used as a source of energy if: Availability of carbohydrates and lipids is low Availability of amino acids exceeds their requirement
- 5. Amino acids areobtained from: Digestion of dietary proteins Breakdown of body proteins Endogenous synthesis EMB-RCG
- 6. Amino acids areused for: Synthesis of body proteins Synthesis of non-protein specialized products Provision of energy EMB-RCG
- 7. In plasma aswell as in tissues, there is an amino acid pool EMB-RCG Amino acids are continuously added to and removed from the pool
- 9. Nitrogen balance Proteins arethe main nitrogenous constituent of our diet Proteins are broken down into amino acids Catabolism of amino acids results in the release of their amino groups in the form of ammonia
- 10. In human beingsand other mammals, ammonia is converted into urea which is excreted in urine Urea is the main nitrogenous compound excreted from the body
- 11. Thus, nitrogen istaken in mostly as proteins and excreted mainly as urea The relative intake and excretion of nitrogen is known as the nitrogen balance
- 12. In healthy adults,nitrogen excretion equals nitrogen intake The person is said to be in nitrogen equilibrium Nitrogen equilibrium
- 13. In growing age,amino acids are used to form tissue proteins Therefore, nitrogen excretion is less than the intake The individual is said to be in a positive nitrogen balance Positive nitrogen balance
- 14. In starvation andwasting diseases, there is excessive breakdown of body proteins Nitrogen excretion exceeds the intake The individual is said to be in negative nitrogen balance Negative nitrogen balance
- 15. Proteins are synthesizedfrom twenty L-amino acids (standard amino acids) in living organisms All these amino acids are equally important for protein synthesis Essential and non-essential amino acids
- 16. However, the presenceof all these amino acids in diet is not imperative Some of these can be synthesized in human beings Amino acids that cannot be synthesized by human beings are nutritionally essential Their presence in diet is imperative
- 17. The essential aminoacids are: • Valine • Leucine • Isoleucine • Threonine • Methionine • Lysine • Phenylalanine • Tryptophan
- 18. Two amino acids,arginine and histidine, are said to be semi-essential Their endogenous synthesis cannot meet the requirements in growing age The remaining amino acids can be synthesized in adequate amounts They are considered to be nutritionally non-essential or dispensable
- 19. Our study ofamino acid metabolism will comprise: • Digestion of proteins and absorption of amino acids • Synthesis of non- and semi- essential amino acids • Catabolism of amino acids • Synthesis of non-protein specialized products from amino acids • Inborn errors of amino acid metabolism
- 20. Proteins are macromolecules Theycannot be absorbed from the alimentary tract as such Dietary proteins have to be hydrolysed into amino acids before their absorption Digestion and absorption
- 21. Proteins are hydrolysedby the proteolytic enzymes present in digestive juices The number of proteins present in the diet is large But the number of proteolytic enzymes in digestive secretions is very small
- 22. The proteolytic enzymespresent in digestive juices are group-specific They are specific for peptide bonds but not for the actual substrate Some are endopeptidases and some are exopeptidases
- 23. The proteolytic enzymesare generally secreted in the form of inactive proenzymes The catalytic site is concealed by a portion of the polypeptide chain in proenzymes Removal of the covering peptide reveals the catalytic site This converts the proenzyme into active enzyme
- 24.
- 25. Conversion of proenzymesinto enzymes occurs only upon entry of food This protects the structural proteins of mucosa against proteolysis by digestive enzymes
- 26. Digestive secretions takingpart in the digestion of proteins are: Gastric juice Pancreatic juice Intestinal secretion (succus entericus) EMB-RCG
- 27. Gastric juice The proteolyticenzyme present in gastric juice is pepsin It is secreted as a proenzyme, pepsinogen Gastric hydrochloric acid splits a peptide off pepsinogen to convert it into pepsin Pepsin, once formed, can convert further molecules of pepsinogen into pepsin EMB-RCG
- 28. Pepsin is anendopeptidase It hydrolyses internal bonds of proteins to convert them into peptides It acts preferentially on peptide bonds formed by aromatic and dicarboxylic amino acids
- 30. Another enzyme, renninis present in the gastric juice of infants It acts on casein of milk, and converts it into calcium paracaseinate Calcium paracaseinate is hydrolysed by pepsin into peptides
- 32. Pancreatic juice Pancreatic juicecontains the proenzymes: Trypsinogen Chymotrypsinogen Proelastase Procarboxypeptidase EMB-RCG
- 33. Pancreatic proenzymes are convertedinto: Trypsin Chymotrypsin Elastase Carboxypeptidase EMB-RCG
- 34. Trypsinogen is convertedinto trypsin by enterokinase Trypsin can convert further molecules of trypsinogen into trypsin EMB-RCG
- 36. Trypsin also converts: Chymotrypsinogeninto chymotrypsin Proelastase into elastase Procarboxypeptidase into carboxypeptidase
- 38. Trypsin, chymotrypsin andelastase are endo-peptidases They hydrolyse proteins and polypeptides into small peptides
- 39. Trypsin acts preferentiallyon peptide bonds formed by basic amino acids Chymotrypsin acts preferentially on peptide bonds in which the carboxyl group is contributed by aromatic amino acids
- 40. Elastase acts preferentiallyon peptide bonds in which the carboxyl group is contributed by glycine, alanine or serine Carboxypeptidase is an exopeptidase which removes amino acids one by one from the carboxyl end of proteins EMB-RCG
- 41. Intestinal secretion Intestinal secretioncontains an amino- peptidase and some dipeptidases Aminopeptidase removes amino acids one by one from the amino end Dipeptidases hydrolyse dipeptides into amino acids
- 43. The final productsof digestion of proteins are L-amino acids These are absorbed by the mucosal cells of the small intestine The absorption is active and energy- consuming
- 44. There are severalactive transport systems for absorption of different groups of amino acids Some of these are linked with sodium pump in the same way as the active transport system for glucose (SGLT 1)
- 45.
- 46. Synthesis of non-and semi-essential amino acids These amino acids can be synthesized in human beings from: Amphibolic intermediates Some other amino acids
- 47. Amino acids synthesizedfrom amphibolic intermediates are: • Glycine • Alanine • Serine • Aspartate • Glutamate
- 49. Alanine can besynthesized from pyruvate by a transamination reaction The reaction is catalysed by glutamate pyruvate transaminase (GPT) Pyridoxal phosphate is required as a coenzyme Alanine
- 51. Aspartate can besynthesized from oxaloacetate by transamination The reaction is catalysed by glutamate oxaloacetate transaminase (GOT) Pyridoxal phosphate is required as a coenzyme Aspartate
- 53. Serine can besynthesized from 3-phospho- glycerate 3-Phosphoglycerate is an intermediate of glycolysis Serine
- 55. Glutamate can besynthesized from a-keto- glutarate The reaction is catalysed by glutamate dehydrogenase NADPH is required as a coenzyme Glutamate
- 57. Amino acids synthesizedfrom other amino acids are: • Glycine • Asparagine • Serine • Glutamine • Cysteine • Tyrosine • Proline • Hydroxyproline • Hydroxylysine • Arginine • Histidine
- 61. Glutamine can besynthesized from glutamate and free ammonia Energy is provided by hydrolysis of ATP into ADP and Pi Glutamine
- 63. Cysteine can besynthesized from methionine and serine These are converted into homoserine and cysteine respectively Cysteine
- 64. S-Adenosyl methionine (SAM;active methionine) is formed as an intermediate during the reactions SAM is a donor of labile methyl groups, and provides methyl groups for several methylation reactions
- 67. Tyrosine can besynthesized by hydroxylation of phenylalanine The reaction is catalysed by phenyl- alanine hydroxylase, a mono-oxygenase One atom of O2 is incorporated in phenyl- alanine; the other is reduced to water Tyrosine
- 68. The hydrogen atomsare provided by tetrahydro-biopterin (H4-biopterin) This is oxidized to dihydrobiopterin (H2-biopterin) H4-Biopterin is regenerated at the expense of NADPH
- 70. Hydroxylation of phenylalanineis an irreversible reaction Therefore, phenylalanine cannot be synthesized from tyrosine
- 71. Proline can besynthesized from glutamate All the reactions are reversible Therefore, glutamate can also be synthesized from proline Proline
- 73. Hydroxyproline is foundin large amounts in collagen There is no codon or anticodon for hydroxyproline Hence preformed hydroxyproline cannot be incorporated in proteins Hydroxyproline
- 74. Proline is incorporatedin the growing polypeptide chain The prolyl residues are later hydroxylated by prolyl hydroxylase This enzyme cannot act on free proline
- 75. Prolyl hydroxylase isa mono-oxygenase It requires a-ketoglutarate as a second substrate It also requires molecular oxygen, ascorbic acid and Fe++
- 77. Hydroxylysine is alsopresent in collagen Like proline, lysine is incorporated in the growing polypeptide chain Then, the lysine residues are hydroxylated by lysyl hydroxylase The reaction is analogous to hydroxylation of proline residues Hydroxylysine
- 79. Arginine is formedby cleavage of argininosuccinate Argininosuccinate is an intermediate in urea cycle Arginine
- 81. The reactions bywhich histidine is synthesized in human beings are not fully known Some authorities believe that human beings cannot synthesize histidine Histidine
- 82. The proteins inour body are in a constant state of flux A protein is degraded when its life-span is over Protein turnover
- 83. Some abnormal andharmful proteins are promptly degraded e.g.: Newly-synthesized proteins that are defective due to errors in translation Proteins that become defective due to oxidative damage Exogenous proteins that enter as components of bacteria, viruses etc
- 84. There are twopathways for degradation of proteins: Lysosomal degradation Cytosolic degradation EMB-RCG
- 85. Lysosomes contain hydrolyticenzymes These include proteolytic enzymes also The lysosomal proteolytic enzymes are known as cathepsins EMB-RCG Lysosomal degradation
- 86. The cathepsins hydrolyse: Proteinshaving long half-lives Circulating proteins Membrane proteins Exogenous microbial proteins residing in endosomes
- 87. No energy isrequired for lysosomal hydrolysis of proteins Loss of sialic acid from the prosthetic group of circulating glycoproteins destines them for destruction These proteins are taken up by hepatocytes with the help of asialoglycoprotein receptors EMB-RCG
- 88. Cytosolic degradation Proteins degradedin the cytosol are: Proteins having short half-lives Defective proteins Exogenous proteins of most viruses and some bacteria EMB-RCG
- 89. EMB-RCG Cytosolic degradation: Is ubiquitin-dependent IsATP-dependent Requires 26 S protease complex (proteasome) Requires three other enzymes (ENZ1, ENZ2 and ENZ3)
- 90. Ubiquitin is aubiquitous protein found in all organisms It is made up of 76 amino acids, and has a molecular weight of 8,500 Primary structure of ubiquitin is remarkably similar in different species EMB-RCG
- 91. Glycine is theC-terminal amino acid residue of ubiquitin It forms a peptide bond with e-amino group of a lysine residue of the target protein If there are more than one lysine residues in the target protein, a number of ubiquitin molecules may attach to it EMB-RCG
- 92. C-terminal glycine ofubiquitin forms a thio- ester bond with the ‒SH group of ENZ1 This reaction is driven by hydrolysis of ATP into AMP and PPi In the second reaction, ENZ1 is replaced by ENZ2 In the presence of ENZ3, ENZ2 is replaced by the target protein
- 94. Once the targetprotein is tagged with ubiquitin, it is destined for destruction The 26S protease complex hydrolyses the target protein Ubiquitin is not hydrolysed and is recycled
- 95. Half-lives of proteinsvary over a wide range Regulatory enzymes usually have half-lives of minutes Circulating proteins have half-lives of weeks Structural proteins have half-lives of years Half-lives of proteins
- 96. Half-life of aprotein is determined by its N- terminal amino acid Proteins having Met, Val, Gly, Thr or Ser at their N-terminus have long half-lives Proteins having Arg, His, Lys, Phe or Asp at their N-terminus have short half-lives EMB-RCG
- 97. A protein isdegraded when its life-span is over ENZ3 recognizes the N-terminal amino acid of the protein and targets it for degradation In adult human beings, the daily protein turnover is 1-2% EMB-RCG
- 98. Three-fourths of theamino acids released from breakdown of proteins are reutilized The remaining amino acids are catabolized
- 99. Catabolism of aminoacids Catabolism of amino acids comprises catabolism of their: Amino groups Carbon skeletons Carbon skeletons of different amino acids have different fates The fate of their amino groups is the same
- 100. The amino groupsof amino acids are removed as ammonia Since ammonia is very toxic, it has to be converted into a non-toxic metabolite In ureotelic organisms, e.g. mammals, ammonia is converted into urea
- 101. Though amino acidsare catabolized in several tissues, urea is synthesized only in liver Liver releases urea in circulation from where it extracted by the kidneys, and is excreted in urine
- 102. Fate of carbonskeletons EMB-RCG The carbon skeletons of amino acids are converted into: Pyruvate or Acetyl CoA or Intermediates of citric acid cycle
- 103. Pyruvate and intermediatesof citric acid cycle (CAC) are substrates for gluconeo- genesis Therefore, amino acids which form pyruvate or CAC intermediates are known as glycogenic amino acids
- 105. Carbon skeletons ofleucine and lysine are converted into acetyl CoA Acetyl CoA can form fatty acids Hence, these two amino acids are known as ketogenic amino acids
- 106. Some amino acidscan form: Acetyl CoA and Pyruvate/CAC intermediates Their carbon skeletons can form glucose as well as fatty acids These are known as glyco- and keto- genic amino acids
- 107. The glyco- andketo-genic amino acids are: Isoleucine Phenylalanine Tyrosine Tryptophan
- 108. Amino acids formingpyruvate are: (i) threonine, (ii) glycine, (iii) serine, (iv) alanine, (v) cysteine and (vi) hydroxyproline Some of these amino acids may have additional fates also Amino acids forming pyruvate
- 110. Glycine, besides formingpyruvate, may also be cleaved into ammonia, carbon dioxide and a methylene moiety Glycine + H4-Folate + NAD+ Methylene-H4-Folate + NH3 + CO2 +NADH + H+ The methylene moiety is taken up by tetrahydrofolate
- 111. Conversion of alanineinto pyruvate occurs by a simple transamination reaction: Alanine + a-Ketoglutarate Pyruvate + Glutamate Glutamate pyruvate transaminase, PLP
- 113. Hydroxyproline Hydroxyproline is catabolisedto pyruvate and glyoxylate via: D1-Pyrroline-3-hydroxy-5-carboxylic acid g-Hydroxyglutamate g-semialdehyde g-Hydroxyglutamate a-Keto-g-hydroxyglutarate
- 115. Intermediates of citricacid cycle formed from amino acids are: a-Ketoglutarate Succinyl CoA Fumarate Oxaloacetate
- 116. Histidine, proline, arginine,glutamine and glutamate form a-ketoglutarate The first four are converted into glutamate which is transaminated to a-ketoglutarate Amino acids forming a-ketoglutarate
- 117. Histidine is convertedinto N-formimino- glutamic acid (FIGLU) The conversion occurs via urocanic acid and 4-imidazolone-5-propionic acid FIGLU transfers its formimino group to H4- folate, and is converted into glutamic acid
- 119. If H4-folate isnot available, FIGLU will not be converted into glutamic acid and urinary FIGLU excretion will be increased Therefore, measurement of urinary FIGLU after a test dose of histidine is an important test for diagnosis of folic acid deficiency
- 120. Arginine is hydrolysedinto urea and ornithine by arginase Ornithine is transaminated to glutamate g- semialdehyde Glutamate g-semialdehyde is oxidised to glutamate The latter is converted into a-keto- glutarate by transamination
- 122. Proline is oxidisedto D1-pyrroline-5- carboxylic acid D1-Pyrroline-5-carboxylic acid is converted into glutamate g-semialdehyde The latter is oxidised to glutamate
- 124. Glutamine is convertedinto glutamate by glutaminase Glutamate is converted into a-keto- glutarate by transamination a-Ketoglutarate enters the citric acid cycle
- 126. Methionine, isoleucine andvaline are catabolised to form succinyl CoA Methionine is converted into S-adenosyl methionine (SAM) SAM acts as a donor of labile methyl groups for various methylation reactions Amino acids forming succinyl coenzyme A
- 127. Conversion of methionineinto homo- serine has been seen earlier Homoserine is deaminated to a-keto- butyrate by homoserine deaminase a-Ketobutyrate is converted into propionyl CoA Propionyl CoA is then converted into succinyl CoA as seen earlier
- 129. Valine, isoleucine andleucine are branched- chain amino acids The first three reactions in their catabolic pathways are similar The first two reactions are catalysed by common enzymes First, these three are converted into their a- keto acid derivatives by transamination
- 130. The a-keto acidsundergo oxidative decarboxylation to their CoA derivatives with one carbon atom less The CoA derivatives are oxidised by removal of two hydrogen atoms From this reaction onwards, the pathways differ
- 131. Valine is convertedinto methylmalonyl CoA Methylmalonyl CoA forms succinyl CoA
- 134. Isoleucine is glyco-and keto-genic Its carbon skeleton is converted into one molecule of propionyl CoA and one molecule of acetyl CoA Propionyl CoA can be converted into succinyl CoA Acetyl CoA can form fatty acids
- 137. A part ofthe carbon skeletons of phenyl- alanine and tyrosine is converted into fumarate as will be seen later The major portion of the carbon skeletons is converted into acetyl CoA Amino acids forming fumarate
- 138. Asparagine and aspartateare catabolized to oxaloacetate Asparagine is first converted into aspartate by a reaction analogous to the conversion of glutamine into glutamate Amino acid forming oxaloacetate
- 139. Aspartate is transaminatedto oxalo- acetate Oxaloacetate is a citric acid cycle intermediate
- 141. Amino acids formingacetyl coenzyme A Acetyl CoA is formed from: Phenylalanine Tyrosine Tryptophan Lysine Leucine
- 142. Phenylalanine is convertedinto tyrosine by phenylalanine hydroxylase as seen earlier The subsequent pathway for catabolism of these amino acids is common Carbon skeletons of phenylalanine and tyrosine are catabolised to fumarate and acetyl CoA Phenylalanine and tyrosine
- 145. Tryptophan is catabolisedto acetoacetyl CoA which can be converted into acetyl CoA The side chain of tryptophan is removed as alanine which can be converted into pyruvate Tryptophan
- 149. In pyridoxine deficiency,3-hydroxykyn- urenine is not converted into 3-hydroxy- anthranilic acid 3-Hydroxykynurenine is converted into an alternate metabolite, xanthurenic acid Xanthurenic acid is excreted in urine
- 150. Laboratory diagnosis ofpyridoxine deficiency can be made by: Giving a test dose of tryptophan Measuring urinary excretion of xanthurenic acid
- 151. Lysine is catabolisedto a-ketoadipic acid a-Ketoadipic acid is converted into acetyl CoA via glutaryl CoA and acetoacetyl CoA Lysine
- 155. Leucine is catabolisedto acetyl CoA and acetoacetate The latter is converted into acetyl CoA via acetoacetyl CoA
- 158. Synthesis of non-proteinspecialized products Hormones PorphyrinsPurines Pigments Specialized products synthesized from amino acids
- 159. The amino acidsforming specialized products are: • Glycine • Methionine • Cysteine • Glutamate • Arginine • Histidine • Tyrosine • Tryptophan
- 160. Glycine acts asa neurotransmitter in brain Many specialized products are formed from glycine For example, the entire glycine molecule is incorporated in the purine nucleus Glycine
- 162. Glycine also formsa part of the porphyrin nucleus Porphyrin synthesis begins with condensation of glycine with succinyl CoA The bile acid, glycocholic acid is formed by conjugation of glycine with cholic acid
- 163. Glycine is usedto synthesize glutathione Glycine can provide a one-carbon unit to tetrahydrofolate It can be converted into serine It can combine with benzoyl CoA to form hippuric acid
- 164. Glycine is usedin the synthesis of creatine also Creatine plays an important role in energy-transfer reactions in muscles It acts as a reservoir of energy in muscles
- 167. For muscle contraction,energy is provided by hydrolysis of ATP to ADP Continued muscle contraction can cause depletion of ATP Creatine phosphate transfers its high-energy phosphate to ADP to regenerate ATP
- 168. When muscles arerelaxing, creatine phosphate is regenerated ATP transfers a high-energy phosphate to creatine forming creatine phosphate This is a reversible reaction catalysed by creatine kinase (CK)
- 170. The biologically importantcompound formed from methionine is S-adenosyl methionine S-adenosyl methionine acts as a donor of labile methyl groups for various methylation reactions Methionine
- 172. Cysteine forms taurinewhich acts as a neuro-transmitter in brain Taurine also conjugates with cholic acid to form taurocholic acid, a bile acid Cysteine is also used in the synthesis of coenzyme A from pantothenic acid Cysteine
- 173. The mercaptoethanolamine portionof coenzyme A is derived from cysteine Cysteine is also a constituent of glutathione
- 175. Gamma-aminobutyric acid actsas a neuro- transmitter in brain as does glutamate itself Glutamate is also used to form glutathione
- 176. The most importantcompounds formed from arginine are creatine and nitric oxide Nitric oxide acts as a local hormone, as a neurotransmitter and as a free radical Arginine
- 178. The local hormone,histamine is formed by decarboxylation of histidine The reaction is catalysed by histidine decarboxylase Histidine
- 180. A number ofspecialized compounds are formed from tyrosine All these compounds can also be formed form phenylalanine after its hydroxylation to tyrosine Tyrosine
- 181. Specialized products formedfrom tyrosine or phenylalanine are: Epinephrine Norepinephrine Tri-iodothyronine (T3) Thyroxine (T4) Melanin
- 182. Epinephrine and norepinephrineare known as catecholamines Phenylalanine/tyrosine is first converted into dihydroxyphenylalanine (DOPA) DOPA is decarboxylated to dopamine, a neurotransmitter
- 184. Dopamine is hydroxylatedto norepinephrine Epinephrine is formed by methylation of norepinephrine
- 186. T3 and T4are formed from tyrosyl residues of thyroglobulin Some tyrosyl residues are converted into mono-iodo-tyrosyl (MIT) residues Some are converted into di-iodo-tyrosyl (DIT) residues
- 187. One MIT andone DIT can form tri-iodo- thyronine (T3) Two DIT residues can form tetra-iodo- thyronine (T4)
- 189. Melanin, the blackpigment present in skin, hair and iris, is formed from tyrosine The exact structure of melanin is not known These two are formed from tyrosine It is believed to be a polymer of 5,6- dihydroxyindole and indole-5,6-quinone
- 191. The hormones, serotoninand melatonin, are synthesized from tryptophan Serotonin is an intermediate in the synthesis of melatonin Tryptophan
- 194. Nicotinic acid (niacin)can also be synthesized from tryptophan 3-Hydroxyanthranilic acid formed during catabolism of tryptophan can be converted into nicotinic acid