Chapter 20-Amino Acid Metabolism

→Step 2: citrulline is formed from ornithine and carbamoyl phosphate by the enzyme ornithine
transcarbamoylase.
→Step 3: :arginosuccinate is formed from citrulline and Aspartic acid via a citrullyl-AMP intermediate by the
enzyme argininosuccinate synthetase. (This step requires 2 ATP)
→Step 4: Argininosuccinate is converted to fumarate (TCA intermediate) and arginine by the enzyme
argininosuccinate lyase.
→Step 5: Arginine is hydrolyzed to form ornithine and urea by the enzyme arginase. The ornithine can then
combine with carbmoyl phosphate to begin the cycle again.
→ Note the "linking" of the Urea Cycle and the TCA cycle (the so-called Krebbs "bicycle").
→Steps 1 and 2 occur in the mitochondria, and steps 3-5 occur in the cytosol. There is a citruline/ornithine
exchange transpoter in the inner mitochondrial membrane.
→The urea then travels to the kidneys for filtration and excretion.
→The main regulation is controlled by need and diet. A high protein diet and starvation activate the cycle.
N-acetylglutamate activates carbamoyl phosphate synthase.
Metabolic Disorders:
NH 3 is toxic because excess NH 3 converts a-ketoglutarate to Glu. This results in a break in the TCA
cycle, reduced ATP, and leads to coma and death.
→The therapy to treat any metabolic disorders that result in a decrease in the urea cycle are (1) limit
protein intake, (2) remove excess NH3 with a compound the will bind the NH3 and be excreted, and (3) replace
TCA cycle intermediates.
Tyrosine Biosynthesis