Lecture 15: Amino Acid Catabolism and Urea Cycle PDF

Lippincott’s illustrated reviews Chapter 19, Page 245 Lecture 15 Amino acid catabolism and Urea cycle 1  Specific Objectives By the end of this lecture students can be able to: Follow the steps for amino...

Lippincott’s illustrated reviews Chapter 19, Page 245 Lecture 15 Amino acid catabolism and Urea cycle 1  Specific Objectives By the end of this lecture students can be able to: Follow the steps for amino acid catabolism. Explain urea cycle. 2  l Amino acid catabolism is part of the larger process of the metabolism of nitrogen-containing molecules. Nitrogen enters the body in a variety of compounds present in food, the most important being amino acids contained in dietary protein. Nitrogen leaves the body as urea, ammonia, and other products derived from amino acid metabolism. The role of body proteins in these transformations involves two important concepts: the amino acid pool and protein turnover. 3 4  Steps for amino acid catabolism 1. Ammonia formation: All amino acids are first transaminated to glutamate, which is then F finally deaminated forming ammonia. 2. Ammonia Trapping How Ammonia is highly toxic especially to the central nervous system. The intracellular ammonia is immediately trapped by glutamic acid to form glutamine especially in brain cells, this called ammonia trapping. s ts Glutamine is a safe substance which can release from all cells and go to liver through blood stream without any toxicity. 5 6 3. Final disposal of ammonia: The glutamine is then transported to liver, where it cleaves by the enzyme glutaminase into ammonia and glutamic acid. Detoxification of ammonia takes place in the liver by immediate conversion of ammonia to urea which excretes through urine. Urea is considered as the end product of protein D8 metabolism a s can be end product of pyrmdine 7 8 9  Kreb's cycle e c I cycle e L r f e_ 10  Reactions of urea cycle Formation of Carbamoyl Phosphate One molecule of ammonia condenses with CO2 in the presence of two molecules of ATP to form carbamoyl phosphate. most important step The reaction is catalyzed by the mitochondrial enzyme carbamoyl phosphate synthetase-I (CPS-I). T wMwewm I CPS-I reaction is the rate-limiting step in urea formation. It is allosterically regulated. 11 Cleavage of Argininosuccinate Argininosuccinate is cleaved to arginine and fumarate by argininosuccinate lyase. The fumarate hydrated to malate providing a link with several metabolic pathway. for example, malate can transported to mitochondria and oxidized to oxaloacetate which used for gluconeogenesis. 12 Fate of urea Urea diffuse from the liver and is transported in the blood to the kidney where filtered and excreted in the urine. A portion of the urea diffuses from blood to intestine where it cleaves by bacterial urease to CO2 and NH3 which partly lost in feces and partly reabsorbed into blood. Trases of amonia is found in healthy because of the intestine 13 14  Patient with kidney failure, plasma urea level is elevated. Ammonia also increase by the action of intestinal bacterial urease. In this case, oral administration of neomycin reduce the number of these bacteria to reduce ammonia production. ougivetntibiotic.IT W also, a patient with hepatic encephalopathy should take lactulose. 1 The mechanism of action is by decreasing the intestinal production and absorption of ammonia. 15 Reference Book: Champe, P. C., Harvey, R. A. and Ferrier, D. R., 2005. Biochemistry “Lippincott’s Illustrated Reviews”, 5th or 6th Edition 16