bioc441 - lecture 22.UreaCycl

bioc441 - lecture 22.UreaCycl - 22 The urea cycle and amino...

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22. The urea cycle and amino acid catabolism and biosynthesis
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NH 4 + ammonium ion uric acid H 2 N-C-NH 2 urea O NH 4 + O O HN N H N H N H O most terrestrial vertebrates fish & other aquatic vertebrates Some animals excrete NH 4 + or uric acid. amino acids The carbon chains are broken down to molecules that feed into the TCA cycle. Most mammals convert amino-acid nitrogen to urea for excretion
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urea arginine NH 2 + NH 3 + H 2 N - C -NH-CH 2 CH 2 CH 2 CH-CO 2 - H 2 O argininosuccinate - O 2 C-CH=CH-CO 2 - fumarate - O 2 C-CH 2 CH- NH 3 + CO 2 - Asp The urea cycle - O 2 C-CH 2 CH- NH - C -NH-CH 2 CH 2 CH 2 CH-CO 2 - NH 3 + CO 2 - NH 2 + O H 2 N - C - NH 2 ATP AMP + PP i HCO 3 - NH 4 + 2 ATP 2 ADP + P i carbamoyl phosphate ornithine citrulline NH 3 + H 2 N-CH 2 CH 2 CH 2 CH-CO 2 - NH 3 + H 2 N - C -NH-CH 2 CH 2 CH 2 CH-CO 2 - O P i H 2 N - C -O-P-O - O O - O mitochondria cytosol
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Incorporation of ammonia into urea begins with formation of carbamoyl phosphate This occurs in the mitochondrial matrix. Carbamoyl-phosphate synthetase-I catalyzes the reaction in three steps, using two molecules of ATP: NH 4 + + HCO 3 - 2 ATP 2 ADP + P i H 2 N - C -O-P-O - O O O - carbamoyl phosphate carbamate HCO 3 - ATP ADP P i NH 4 + ATP ADP carbonic- phosphoric acid anhydride O O O - HO-C -O-P-O - H 2 N - C -O - O (1) (2) (3) H 2 N - C -O-P-O - O O O -
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carbamoyl phosphate P i ornithine citrulline This step also occurs in the mitochondrial matrix. Carbamoyl phosphate reacts with ornithine to form citrulline + H + H 2 N - C -O-P-O - O O O - NH 3 + + H 3 N-CH 2 CH 2 CH 2 CH-CO 2 - NH 3 + H 2 N - C -NH-CH 2 CH 2 CH 2 CH-CO 2 - O
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This reaction occurs only in the cytosol, so citrulline first must leave the mitochondria. A transporter exchanges ornithine for citrulline plus a proton across the mitochondrial inner membrane. Combination of citrulline with aspartate to form argininosuccinate is driven by breakdown of ATP to AMP ATP AMP + PP i + H 2 O aspartate argininosuccinate citrulline NH 3 + H 2 N - C -NH-CH 2 CH 2 CH 2 CH-CO 2 - O - O 2 C-CH 2 CH- NH 3 + CO 2 - - O 2 C-CH 2 CH- NH - C -NH-CH 2 CH 2 CH 2 CH-CO 2 - NH 3 + CO 2 - NH 2 +
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This reaction occurs in the cytosol. Argininosuccinate splits into arginine and fumarate - O 2 C-CH=CH-CO 2 - fumarate argininosuccinate arginine - O 2 C-CH 2 CH- NH - C -NH-CH 2 CH 2 CH 2 CH-CO 2 - NH 3 + CO 2 - NH 2 + NH 2 + NH 3 + H 2 N - C -NH-CH 2 CH 2 CH 2 CH-CO 2 -
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This reaction occurs in the cytosol. To continue the cycle, ornithine must return to a mitochondrion. Hydrolysis of arginine releases urea and regenerates ornithine
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This note was uploaded on 04/15/2010 for the course BIOC 441 taught by Professor Young&parson during the Spring '08 term at University of Washington.

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bioc441 - lecture 22.UreaCycl - 22 The urea cycle and amino...

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