Lecture 10 - Protein Turnover and Amino Acid Catabolism
Lecture 10 - Protein Turnover and Amino Acid Catabolism
Lecture 10 - Protein Turnover and Amino Acid Catabolism
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Urea Cycle<br />
Ammonium ion is converted into urea in the<br />
liver.<br />
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4. The Urea Cycle
high ammonia levels are toxic to humans. A complete (or<br />
less severe partial) lack or mutant of one or more of urea<br />
cycle enzymes due to genetic defects leads to<br />
hyperammonemia which is fatal( since there is no known<br />
quantitative alternative pathway for the synthesis of<br />
urea). The toxicity of ammonia is due to its depletion of<br />
alpha-ketoglutarate intermediate of CAC pathway <strong>and</strong><br />
impairment of ATP production(ammonia+ alphakjetoglutarate=<br />
glutamate). Hyperammonemia leads to<br />
mental damage, coma <strong>and</strong> death if not diagnosed <strong>and</strong><br />
treated. Liver cirrhosis due to any causes can lead to<br />
hyperammonemia even with normal urea cycle enzymes<br />
activites; referred to hepatic coma.(all hepatocells are<br />
enzymes).<br />
dead so lack
1. Formation of Carbamoyl Phosphate<br />
Carbamoyl synthetase<br />
Free NH4 reacts with HCO3 to form carbamoyl<br />
phosophate.<br />
Reaction is driven by the hydrolysis of two<br />
molecules of ATP<br />
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2. Formation of Citrulline<br />
Ornithine transcarbamoylase<br />
Citrulline is formed from transfer of the carbamoyl<br />
group to the γ-amino group of ornithine.<br />
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3. Formation of Arginosuccinate<br />
Condensation of citrulline with aspartate to<br />
form arginosuccinate<br />
Two equivalent of ATP are required.<br />
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4. Formation of Arginine <strong>and</strong> Fumarate<br />
Arginosuccinase<br />
Cleaves arginosuccinate to form arginine <strong>and</strong><br />
fumarate<br />
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5. Formation of Urea<br />
Arginase<br />
The arginine is hydrolyzed to produce the urea <strong>and</strong><br />
to reform the ornithine.<br />
The ornithine reenters the mitochondrial matrix.<br />
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