10 urea cycle2


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10 urea cycle2

  1. 1. Amino Acid Breakdown: No storage form of Amino Acids, therefore excess need to be converted to other forms to be used as energy or stored as glycogen/fat. R O H2N CH C OHDisposal of Nitrogen Recycling of theAtom (Urea) Carbon Skeleton
  2. 2. Flow of Nitrogen: In tissues (e.g Muscle), most amino acids transfer theira-amino group to Glutamate Aminotransferase B6 a-ketoglutarate
  3. 3. The N is then transferred from Glutamateto Pyruvate, producing Alanine. a-ketoglutarate Pyruvate Aminotransferase
  4. 4. Four of the amino acids,Glycine, Lysine, Threonineand Serine are directlydeaminated. Serine Dehydratase
  5. 5. NH3 released from Glycine/Lysine/Threonine/Serineis incorporated into Glutamine [ ] Glutamine Synthetase
  6. 6. In sum: During amino acid breakdown, the a -amino Nitrogen getsincorporated as the a-amino group in Alanine or the amide groupin Glutamine. Alanine and Glutamine are then released to the circulation.
  7. 7. Flow of Nitrogen: Alanine and Glutamine released by peripheral tissues aretaken up by the Liver.The Nitrogen on Alanine is transferred to a-ketoglutarateto produce Glutamate
  8. 8. a-ketoglutarate Glutamate Aminotransferase
  9. 9. Glutamate has two fates important for disposal of waste N.1) Conversion to a-ketoglutarate by Glutamate Dehydrogenase to release NH32) As N donor in the transamination of oxaloacetate to Aspartat
  10. 10. 1) Conversion to a-ketoglutarate by Glutamate Dehydrogenase to release NH3 [ ] Glutamate dehydrogenase
  11. 11. 2) As N donor in the transamination of oxaloacetate to Aspartat Glutamate a-ketoglutarate O OO O NH2 O B6HO-C-CH2-C-C-OH HO-C-CH2-CH-C-OH Aminotransferase Oxaloacetate Aspartate
  12. 12. Glutamine is hydrolyzed by Glutaminase to release NH3 Glutaminase NH3
  13. 13. Nitrogen flow in LiverAlanine Glutamate Aspartate NH3Glutamine NH3
  14. 14. Carbomyl Phosphate Synthetase INet reaction:HCO3 + NH3 + 2 ATP Carb-Phos + 2 ADP + Pi(CO2 + NH4)
  15. 15. Glutamate
  16. 16. OAllosteric: C-OH CH2 N-Acetyl Glutamate O CH2 CH3-C-NH-CH-C-OH + O Carbomyl Phosphate Synthetase IHCO3 + NH4
  17. 17. Metabolic Diseases of the Urea Cycle Arginase Deficiency Argininosuccinic acidemia Type II Hyperammonemi Citrullinuria a: Type I
  18. 18. Metabolic Diseases of the Urea Cycle Disorders present in infants: Symptoms: Lethargy, swelling of the brain leads to mental retardation/brain damage Diagnosis: Low blood urea nitrogen (BUN) levels -high levels of ammonia in the blood elevated circulating glutamine -other metabolites that accumulate depend on the specific enzyme defect Most common form: Hyperammonemia Type II caused by Ornithine Transcarbamylase deficiency Elevated Carb-P levels in this deficiency cause secondary problems in pyrimidine metabolism
  19. 19. Treatment: Long term, dietary restriction. Low protein diet. Supplemented with Arginine Short term Dialysis Administration of Nitrogen “scavengers” e.g. Phenylacetate
  20. 20. Treatment of Hyperammonemia with Phenylacetate:taking advantage of metabolism