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22. The urea cycle and amino acid catabolism and biosynthesis

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22. The urea cycle and amino acid catabolism and biosynthesis

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    1. 22. The urea cycle and amino acid catabolism and biosynthesis

    2. Most mammals convert amino-acid nitrogen to urea for excretion

    3. The urea cycle Historical note: Hans Krebs discovered the urea cycle in 1937, 5 years before he discovered the TCA cycle.Historical note: Hans Krebs discovered the urea cycle in 1937, 5 years before he discovered the TCA cycle.

    4. Incorporation of ammonia into urea begins with formation of carbamoyl phosphate

    5. Carbamoyl phosphate reacts with ornithine to form citrulline

    6. Combination of citrulline with aspartate to form argininosuccinate is driven by breakdown of ATP to AMP At physiological pH, ornithine is present mainly as a singly charged cation, whereas citrulline is present mainly as the zwitterion. Exchange of ornithine for citrulline + a proton therefore is electrically neutral but is favored by the pH gradient across the membrane.At physiological pH, ornithine is present mainly as a singly charged cation, whereas citrulline is present mainly as the zwitterion. Exchange of ornithine for citrulline + a proton therefore is electrically neutral but is favored by the pH gradient across the membrane.

    7. Argininosuccinate splits into arginine and fumarate

    8. Hydrolysis of arginine releases urea and regenerates ornithine

    9. Formation of urea consumes 4 phosphate anhydride bonds

    10. The aspartate consumed in the urea cycle can be regenerated from the fumarate that is produced

    11. Oxidation of malate in mitochondria generates ATP

    12. Transport systems in the mitochondrial inner membrane exchange aspartate for glutamate and a-ketoglutarate for malate N. Ramoz et al. Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism, Am. J. Psychiatry 161: 662-669 (2004)N. Ramoz et al. Linkage and association of the mitochondrial aspartate/glutamate carrier SLC25A12 gene with autism, Am. J. Psychiatry 161: 662-669 (2004)

    13. ????a-ketoglutarate/malate and aspartate/glutamate transporters also participate in oxidation of cytosolic NADH

    14. The E. coli lactose permease provides a model for other small-molecule transporters

    15. The mitochondrial ATP/ADP exchanger (translocase) also has a central cavity that opens to the solution on one side of the membrane

    16. The urea cycle is regulated in two ways N-acetylGlu is hydrolyzed by a specific hydrolase. In mammals, N-acetylGlu appears to serve only as a regulatory agent.N-acetylGlu is hydrolyzed by a specific hydrolase. In mammals, N-acetylGlu appears to serve only as a regulatory agent.

    17. Inherited disorders of the urea cycle can have severe effects

    18. Autism is a neurodevelopmental genetic disorder The SNPs are intronic. Deficiencies in the Asp/Glu exchanger could have other effects on mitochondrial metabolism in addition to impairing the urea cycle.The SNPs are intronic. Deficiencies in the Asp/Glu exchanger could have other effects on mitochondrial metabolism in addition to impairing the urea cycle.

    19. Genetic deficiencies in some of the urea-cycle enzymes can be treated pharmacologically

    20. Arginine also serves as a precursor of nitric oxide (NO) Drugs for erectile disfunction (e.g., Viagra) specifically inhibit the cGMP phosphodiesterase.Drugs for erectile disfunction (e.g., Viagra) specifically inhibit the cGMP phosphodiesterase.

    21. The carbon chains of the common amino acids provide materials that feed into the citric acid cycle

    22. Amino acids can be classified as glucogenic or ketogenic

    23. Humans can synthesize 10 of the 20 common amino acids

    24. Building blocks for synthesis of non-essential amino acids in humans come from glycolysis and the citric acid cycle

    25. Serine is formed via 3-phosphoglycerate

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