Amino Acid Metabolism : Amino Acid Metabolism Maninder kaur
NIPER HYD Slide 2: 2 Dynamics of Protein
And Amino Acid Metabolism Dietary Proteins Digestion to Amino Acids
Transport in Blood to Cells Protein Synthesis Functional Proteins
Protein Degradation In
Tagging With Ubiquitin Amino Acids
Metabolites Slide 3: 3 Digestion of Proteins Stomach: Pepsinogen Pepsin (max. act. pH 2)
Small Intestine: Trypsinogen Trypsin
Chymotrypsinogen to chymotrypsin
Proelastase to elastase
Procarboxypeptidase to carboxypeptidase
Aminopeptidases (from intestinal epithelia) Enteropeptidase Slide 5: Gastrin/HCL; Secretin/Biocarbonate; cholecystokinin/release pancreatic zymogens Amino Acid Metabolism : Amino Acid Metabolism Metabolism of the 20 common amino acids is considered from the origins and fates of their: (1) Nitrogen atoms (2) Carbon skeletons
For mammals: Essential amino acids must be obtained from dietNonessential amino acids - can be synthesized The Nitrogen Cycle and Nitrogen Fixation : The Nitrogen Cycle and Nitrogen Fixation Nitrogen is needed for amino acids, nucleotides
Atmospheric N2 is the ultimate source of biological nitrogen
Nitrogen fixation: a few bacteria possess nitrogenase which can reduce N2 to ammonia
Nitrogen is recycled in nature through the nitrogen cycle Fig 17.1 The Nitrogen cycle : Fig 17.1 The Nitrogen cycle Nitrogenase : Nitrogenase 17.2 Assimilation of Ammonia : 17.2 Assimilation of Ammonia Ammonia generated from N2 is assimilated into low molecular weight metabolites such as glutamate or glutamine
At pH 7 ammonium ion predominates (NH4+)
At enzyme reactive centers unprotonated NH3 is the nucleophilic reactive species A. Ammonia Is Incorporated into Glutamate : A. Ammonia Is Incorporated into Glutamate Reductive amination of a-ketoglutarate by glutamate dehydrogenase occurs in plants, animals and microorganisms
In mammals & plants, located in mitochondria. B. Glutamine Is a Nitrogen Carrier in Many Biosynthetic Reactions : B. Glutamine Is a Nitrogen Carrier in Many Biosynthetic Reactions A second important route in assimilation of ammonia is via glutamine synthetase Transamination Reactions : Transamination Reactions Transfer of an amino group from an a-amino acid to an a-keto acid
In amino acid biosynthesis, the amino group of glutamate is transferred to various a-keto acids generating a-amino acids
In amino acid catabolism, transamination reactions generate glutamate or aspartate Transaminations : 14 Transaminations Glutamate a-Ketoglutarate
Oxaloacetate Aspartate Glutamate-Pyruvate
(Alanine Transferase ALT) Glutamate-Oxaloacetate
(Aspartate Transferase AST) Blood levels of these aminotransferases, also called transaminases,
are important indicators of liver disease Fig 17.6 Transamination reactions : Fig 17.6 Transamination reactions Slide 16: Glutamine and glutamate are “collection points”. Hepatocyte cytosol/mitochondria Urea Cycle : Urea Cycle The urea cycle was the first metabolic process to be described as a cycle by Sir Hans Krebs who also described the TCA cycle.
Role of Urea cycle: rid the body of toxic NH 4 + therefore permitting the use of AA as an energy source.
Liver major site of urea synthesis, major source of arginase, (small amounts in small intestine) and is the only tissue with the complete set of all 5 enzymes required Slide 20: Urea Cycle Short term Regulation: CPS1 : Short term Regulation: CPS1 1. NAG(N-acetyl glutamate), a positive allsoteric regulator is absolutely required.
Alters enzyme conformation
2. NAG is synthesized in liver mitochondria from acetyl CoA and GLU
FA or pyruvate acetyl CoA
Diet or tissue proteins AA GLU and ARG
Acetyl CoA + GLU NAG (enzyme = NAG synthase)
3. NAG synthesis is markedly stimulated by ARG (allosteric) but not completely dependent ( V max) therefore AA NAG Slide 23: Regulation via NAG Regulation through Mg2+ : Regulation through Mg2+ (i) Mg2+: CPS1 dependent Mg2+ ( both ATP and free)
Therefore changes in mitochondrial citrate can affect reaction since citrate chelates Mg2+
(ii) Zn2+ is present in mitochondria
Zn2+ decreases CPSI activity in vitro
However, AA (ornithine) can chelate Zn therefore preventing inhibition of CPS1. Slide 26: Defects of Urea Cycle ↑ orotic acid III IV V Treatment for deficiencies in urea cycle Enzymes : Treatment for deficiencies in urea cycle Enzymes Slide 28: Metabolism of Individual Amino Acid Overview : Overview Overview (cont) : Overview (cont) Synthesis of Serine and Glycine : Synthesis of Serine and Glycine Catabolic pathways for Glycine : Catabolic pathways for Glycine Synthesis of Specialized products : Synthesis of Specialized products Formatin of Oxalate
Formation of Purine ring.
Synthesis of Glutathione.
Synthesis of heme
Biosynthesis of Creatine Biosynthesis of hippurate. : Biosynthesis of hippurate. Biosynthesis and metabolism of creatine and creatinine. : Biosynthesis and metabolism of creatine and creatinine. Biosynthesis of porphobilinogen. : Biosynthesis of porphobilinogen. Heme Biosynthetic Pathway. : Heme Biosynthetic Pathway. Biosynthesis of glutathione : Biosynthesis of glutathione Slide 42: Aromatic Amino Acids Pathway to Chorismate : Pathway to Chorismate Synthesis of Phenylalanine & Tyrosine. : Synthesis of Phenylalanine & Tyrosine. Synthesis of Tyrosine and Phenylalanine : Synthesis of Tyrosine and Phenylalanine Synthesis of Tyrosine and Phenylalanine (cont) : Synthesis of Tyrosine and Phenylalanine (cont) Catabolic pathways for phenylalanine & tyrosine : Catabolic pathways for phenylalanine & tyrosine Biosynthesis of plant substances from amino acids. : Biosynthesis of plant substances from amino acids. Specialized Products : Specialized Products Synthesis of Catecholamines
Synthesis of Thyroid hormones.
Synthesis of Melanin pigment Alternative pathways for catabolism of phenylalanine in phenylketonuria. : Alternative pathways for catabolism of phenylalanine in phenylketonuria. Slide 55: Tryptophan Catabolism of L-tryptophan. : Catabolism of L-tryptophan. Tryptophan as precursor : Tryptophan as precursor Sulphur Containing amino acids : Sulphur Containing amino acids Methionine
Cystine Synthesis of methionine & S-adenosylmethionine in an activated-methyl cycle. : Synthesis of methionine & S-adenosylmethionine in an activated-methyl cycle. Conversion of spermidine to spermine. : Conversion of spermidine to spermine. Conversion of methionine to Cysteine & Propionyl-CoA : Conversion of methionine to Cysteine & Propionyl-CoA The cystine reductase reaction. : The cystine reductase reaction. Catabolism of L-cysteine : Catabolism of L-cysteine Catabolic pathways for the three branched-chain amino acids: valine, isoleucine, and leucine. : Catabolic pathways for the three branched-chain amino acids: valine, isoleucine, and leucine. Catabolism of the β-methylcrotonyl-CoA formed from L-leucine. : Catabolism of the β-methylcrotonyl-CoA formed from L-leucine. Subsequent catabolism of the tiglyl-CoA formed from L-isoleucine. : Subsequent catabolism of the tiglyl-CoA formed from L-isoleucine. Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline. : Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline. Biosynthesis and metabolism of creatine and creatinine. : Biosynthesis and metabolism of creatine and creatinine. Summary of amino acid Catabolism : Summary of amino acid Catabolism Some enzyme cofactors important in one-carbon transfer reactions. : Some enzyme cofactors important in one-carbon transfer reactions. Slide 74: Thanks for your patience listening