Amino Acid Metabolism.

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Section M Nitrogen metabolism

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Amino Acid Metabolism

Role of Amino Acids Protein monomeric units Energy source Precursors of other biological molecules

Protein Monomeric Units

Energy Source

Precursors (Nitrogen-containing Compounds) Heme Nucleotides Amines Nucleotide Coenzymes Glutathione

Precursors (a-ketoacids)

Classification (Mammals) Essential amino acids Non-essential amino acids

Amino Acid Deamination (First Reaction in Amino Acid Breakdown)

Aminotransferases (Transaminases)

Oxidative Deamination

Amino Acid Oxidase

Transamination (Reactions)

Summary

Degradative Fates of Glutamate Regeneration of a-Ketoglutarate

Glutamate-Aspartate Aminotransferase

Glutamate Dehydrogenase (Oxidative Deamination)

Formation of Urea

Degradative Fates of Glutamate Regeneration of a-Ketoglutarate

Urea Cycle

Urea Cycle (Introduction)

Nitrogen Waste Products

Classification of Organisms (Nitrogen Excretion Patterns) Ammonotelic: ammonia excreting Ureotelic: urea excreting Uricotelic: uric acid excreting

Overall Urea Cycle (Liver)

Glutamate Dehydrogenase (Generation of NH3)

Carbamyl Phosphate Synthetase (CPS) (Mitochondrion)

Carbamyl Phosphate Synthetase (CPS) CPSI (Mitochondria) Uses NH3 Urea Cycle CPSII (Cytosol) Uses Glutamine Pyrimidine Biosynthesis

Ornithine Transcarbamylase (OTC) (Mitochondrion)

Glutamate Dehydrogenase

Regeneration of Aspartate (Cytosol)

Oxidation of 2 NADH Yields 6 ATP

Activator

Products of Amino Acid Breakdown Glucogenic Pyruvate – a-Ketoglutarate Succinyl-CoA Fumarate Oxaloacetate Ketogenic Acetyl-CoA Acetoacetate

Degradation of amino acids to one of seven common metabolic intermediates. Page 995

Animals cannot carryout net synthesis of precursors of gluconeogenesis from acetyl-CoA or acetoacetate

Conversion of Pyruvate and Oxaloacetate to PEP (Gluconeogenesis)

Degradation to Pyruvate Alanine, Cysteine, Glycine, Serine and Threonine

Degradation of amino acids Amino acid breakdown can yield: Acetyl-CoA -a-KG Succinyl-CoA OAA fumarate

a-KG is generated from five amino acids Proline Glutamate Glutamine Arginine Histidine

Four amino acids are converted to Succinyl-CoA Methionine Converted to homocysteine through methyl group transfer, generates cysteine as converted to a-ketobutyrate Isoleucine Transamination, oxidative decarboxylation to acetyl-CoA and propionyl CoA Valine Transamination, decarboxylation to propionyl CoA Threonine - a-ketobutyrate generated and converted to propionyl CoA

Propionyl-CoA is a common intermediate for amino acids  succinyl-CoA

Branched-chain a-keto acid dehydrogenase complex In certain body tissues, this enzyme catalyzes the oxidative decarboxylation of valine, isoleucine, and leucine yielding CO2, and acyl-CoA derivatives. Shares ancestry with pyruvate dehydrogenase complex, a-KG dehydrogenase complex – another example of gene duplication

Branched-chain …complex

Asparagine and aspartate are degraded to OAA

Fate of metabolites derived from amino acids In addition to feeding the citric acid cycle, amino acids can result in ketone bodies, while others are gluconeogenic

Ketone bodies The six amino acids that are degraded to acetoacetyl-CoA and/or acetyl-CoA) can be converted to acetoacetate and b-hydroxybutyrate

Glucogenic amino acids Amino acids that are degraded to pyruvate, a-KG, succinyl-CoA fumarate, and/or OAA can be converted to glucose