1 / 29

Catabolism of proteins and amino acids

Catabolism of proteins and amino acids. Reactions in the attachment of ubiquitin to proteins. Relationships among major pathways in nitrogen catabolism. The alpha amino acid nitrogen is channeled into glutamate. Transaminase Roles.

yasir-wheeler
Télécharger la présentation

Catabolism of proteins and amino acids

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Catabolism of proteins and amino acids

  2. Reactions in the attachment of ubiquitin to proteins

  3. Relationships among major pathways in nitrogen catabolism

  4. The alpha amino acid nitrogen is channeled into glutamate.

  5. Transaminase Roles Transaminases equilibrate amino groups among available a-keto acids. This permits synthesis of non-essential amino acids, using amino groups from other amino acids & carbon skeletons synthesized in a cell. Thus a balance of different amino acids is maintained, as proteins of varied amino acid contents are synthesized. Although the amino N of one amino acid can be used to synthesize another amino acid, N must be obtained in the diet as amino acids (proteins).

  6. Transaminases function in amino acid catabolism and biosynthesis

  7. Example of a Transaminase reaction: • Aspartate donates its amino group, becoming the a-keto acid oxaloacetate. • a-Ketoglutarate accepts the amino group, becoming the amino acid glutamate.

  8. The prosthetic group of Transaminase is pyridoxal phosphate (PLP), a derivative of vitamin B6.

  9. In the resting state, the aldehyde group of pyridoxal phosphate is in a Schiff base linkage to the e-amino group of an enzyme lysineresidue.

  10. The a-amino group of a substrate amino aciddisplaces the enzyme lysine, to form a Schiff base linkage to PLP. The (+) charged N of PLP acts as an electron sink, to facilitate catalysis. Lysine extracts H+, promoting tautomerization, followed by reprotonation & hydrolysis.

  11. What was an amino acid leaves as an a-keto acid. The amino group remains on what is now pyridoxamine phosphate (PMP). A different a-keto acid reacts with PMP and the process reverses, to complete the reaction.

  12. Deamination of Amino Acids Transaminases also function to funnel amino groups from excess dietary amino acids to those amino acids (e.g., glutamate) that can be deaminated. Carbon skeletons of deaminated amino acids can be catabolized for energy, or used to synthesize glucose or fatty acids for energy storage. Only a few amino acids are deaminated directly.

  13. Glutamate Dehydrogenase catalyzes the major reaction that accomplishes net removal of N from the amino acid pool.It is one of the few enzymes that can use NAD+ or NADP+ as e- acceptor. Oxidation at the a-carbon is followed by hydrolysis, releasing NH4+.

  14. Glutamate Dehydrogenase

  15. Summarized above: the role of transaminases in funneling amino N to glutamate, for deamination via Glutamate Dehydrogenase, producing NH4+.

  16. Amino Acid Oxidase

  17. Glutamine Synthetase

  18. Glutaminase

  19. Muscle and liver play major roles in maintaining steady-state levels of amino acids

  20. Glucose-Alanine Cycle

  21. Amino acid exchange between organs

  22. Most terrestrial land animals convert excess nitrogen to urea, a compound less toxic than ammonia, prior to excreting it. The Urea Cycle occurs mainly in liver. The 2 nitrogen atoms of urea enter the Urea Cycle as NH3 (most via Glutamate Dehydrogenase) and as amino N of aspartate.

  23. Urea Cycle

  24. Carbamoyl Phosphate Synthase is the committed step of the Urea Cycle, and is subject to regulation. Carbamoyl Phosphate Synthase is allosterically activated by N-acetylglutamate. This derivative of glutamate is synthesized when cellular [glutamate] is high, signaling excess of free amino acids due to protein breakdown or dietary intake.

  25. Hyperammonemia Disease Hereditary deficiency of any of the Urea Cycle enzymes leads to hyperammonemia - elevated [ammonia] in blood. Total lack of any Urea Cycle enzyme is lethal. Elevated ammonia is toxic, esp. to the brain. If not treated immediately after birth, severe mental retardation results.

  26. Postulated mechanisms for toxicity of high [ammonia] High NH3 would drive Glutamine Synthase: glutamate + ATP + NH3 glutamine + ADP + Pi This would deplete glutamate – a neurotransmitter & precursor for synthesis of the neurotransmitter GABA. Depletion of glutamate & high ammonia level would drive Glutamate Dehydrogenase reaction to reverse: glutamate + NAD(P)+ a-ketoglutarate + NAD(P)H + NH4+ The resultingdepletion of a-ketoglutarate, an essential Krebs Cycle intermediate would impair energy metabolism in the brain.

  27. Hyperammonemia Disease Treatment of deficiency of Urea Cycle enzymes (depends on which enzyme is deficient): • limiting protein intake to the amount barely adequate to supply amino acids for growth, while adding to the diet the a-keto acid analogs of essential amino acids. • Liver transplantation has also been used, since liver is the organ that carries out Urea Cycle.

  28. Other disorders associated with the urea cycle • Citrulinemia - • lack of argininosuccinate synthase activity • 1-2 g citruline is excreted per day • Argininosuccinicaciduria - • absence of argininosuccinase activity • high levels of argininosuccinate in blood, urine, cerebrospinal fluid • Hyperargininemia - • low levels of arginase activity • elevated levels of arginine in blood and cerebrospinal fluid

More Related