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31 AAs - Urea Cycle - Amino Acids and Proteins Metabolism...

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Amino Acids and Proteins: Metabolism: The Urea Cycle HNFE 3025 Fall 2009
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Amino Acid Catabolism Overview Begins with the removal of nitrogen Transamination or deamination of amino acids Transamination = transfer of the amino group from an AA to an α -keto acid Deamination = removal of the amino group – producing ammonium (NH 4 + ) The resulting α -keto acid can be further metabolized to pyruvate, acetyl CoA or other TCA cycle intermediates 2
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Amino acid nitrogen will ultimately appear in the urine as nitrogen atoms in urea (mostly) creatinine (from creatine) uric acid (from nucleic acid bases) Elevated serum uric acid can cause a form of arthritis called gout and kidney stones Elevations can result from high intake of purine-rich foods (beer, anchovies, yeast, legumes, mushrooms, spinach, asparagus), high fructose intake, and impaired excretion by the kidneys Associated with CVD, type 2 DM, and Metabolic syndrome Also a potent antioxidant and NH 4 + Amino acid carbon atoms will ultimately appear as CO 2 through oxidation (either directly or indirectly) AA Components Have Different Fates NH 2 H 2 N C O Urea 3
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Amino group removed via either transamination or deamination Amino group (nitrogen, N) used for: proteins and other N-containing compounds excretion as urea (made in urea cycle) or ammonia Carbon skeleton used for: synthesis of glucose (GNG) MOSTLY, or: oxidized for energy, following conversion to acetyl CoA and/or TCA cycle intermediates. General Handling of Excess AAs 4
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Role of pyridoxal 5'-phosphate (PLP): the coenzyme form of vitamin B6 plays a key role in all transamination and some deamination reactions Transamination Involves an α -amino group from an AA being transferred to the α -keto position of an α -keto acid. During this process the α -keto acid acceptor becomes an α -amino acid, and the amino donor becomes an α- keto acid. Deamination Involves the removal of an amino group from an AA with no direct transfer to another compound – product is ammonium (as NH 4 + ) Transamination and Deamination 5
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Catalyzed by PLP-dependent aminotransferases General Transamination Reaction COO - CH 2 CH 2 C NH 3 + H COO - R C O COO - COO - CH 2 CH 2 C O COO - R C NH 3 + COO - H + + α- Keto acid α- KG α- Amino acid Glutamic acid -------------- amino acid 1 + α -keto acid 2 α -keto acid 1 + amino acid 2 6
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Also known as Aspartate transaminase (AST) Old name glutamic oxaloacetic transaminase (GOT) Aspartate Aminotransferase 7 COO -
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