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Amino Acid Catabolism

Amino Acid Catabolism

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Amino Acid Catabolism

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  1. Amino Acid Catabolism C483 Spring 2013

  2. 1. Which of the following is/are true statement(s) about glutamine and alanine? A) They are nitrogen donors in many biosynthetic reactions. B) They are part of the urea cycle. C) They carries nitrogen between tissues, thus avoiding high toxic levels of NH4+ in blood. D) In mammal liver, they receive net nitrogen from glutamate in transaminations. 2. What would be the product of the transamination of the structure shown below? (The unionized forms are shown.)

  3. 3. ATP is required to degrade many proteins because it is required to A) form the proteosome. B) attach ubiquitin to the target protein. C) hydrolyze a ubiquitinated protein. D) All of the above. 4. The enzyme ________ is one of the most abundant in liver mitochondria and catalyzes the synthesis of the molecule shown below. A) arginase B) carbamoyl phosphate synthetase I C) 4-α-carbinolaminedehydratase D) transaminase 5. Which of the following is false concerning the urea cycle? A) Ornithine acts catalytically in the urea cycle. B) Metabolic disease can result from lack of urea cycle enzymes. C) The four reactions of the cycle take place in the liver mitrochondrial matrix. D) One molecule of urea is produced at the cost of 4 ATP equivalents.

  4. Overview • Protein Turnover • Amino Acid Catabolism • Nitrogen pathways • Carbon backbone • From perspective of human metabolism Juicy Steak Part 2

  5. Digestion

  6. Protein Degradation • All proteins have a “half-life” • Part of regulation • Also important in misformed/ mutant proteins • Ubituitin

  7. Marked for destruction • Complex system guards against marking “good” proteins • Costs ATP • Proteasome • Nucleophile hidden in barrel

  8. Amino Acid Degradation • Nitrogen processing is the first step • Then carbon chain is metabolized • Example: • Two nitrogen transfer reactions

  9. Reaction1: Transamination • All amino acids shuttle their nitrogen toward glutamate

  10. Transamination • Not an overall Redox reaction • Requires PLP

  11. Reaction 2: Oxidative Deamination • What happens to all the glutamate? • Glutamate Dehydrogenase

  12. Nitrogen Processing on Tissue Level • The alanine-glucose cycle Amino Acids

  13. Nitrogen Processing on Tissue Level • Glutamine can act as • Ammonia transporter (like alanine) • Substrate in biosynthesis requiring amino groups

  14. Role of Liver Mitochondia • Sequester toxic ammonia • Make less toxic, execrable form • Urea Cycle

  15. Carbamoyl phosphate • Cost of 2 ATP • Phosphate leaving group • Activation of ammonia for • Excretion • biosynthesis

  16. Chemistry of Urea Cycle • Catalytic ornithine • Fumarate • Urea = 4 ATP + ATP + AMP

  17. Solving Metabolic Problems • Arginosuccinase deficiency • Low protein diet • Minimize ammonium • High arginine diet • Provide carrier excreted X

  18. Urea Cycle: Compartmentalization • Ammonia locked into matrix • Urea released • Uses glutamate/ aspartate shuttle

  19. Summary: Main Players • Glutamate: receives nitrogen from AA, then ammonia is released in liver mitochondria • Glutamine: ammonia transport; biosynthesis • Alanine: ammonia transport • Aspartate: nitrogen donor to urea • Arginine: urea cycle

  20. Answers • C • III • D • B • C