Amino Acid Metabolism

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Presentation Transcript

Amino Acid Metabolism : 

Amino Acid Metabolism Maninder kaur M.S (Pharm) 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 Proteasomes Following Tagging With Ubiquitin Amino Acids Metabolites

Slide 3: 

3 Digestion of Proteins Stomach: Pepsinogen Pepsin (max. act. pH 2) Small Intestine: Trypsinogen Trypsin Trypsin cleaves: 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 + + Pyruvate Alanine Glutamate a-Ketoglutarate + + Oxaloacetate Aspartate Glutamate-Pyruvate Aminotransferase (Alanine Transferase ALT) Glutamate-Oxaloacetate Aminotransferase (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. Conjugation reaction. 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 Cysteine 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