Question

The rate limiting step in the urea cycle is catalyzed by which enzyme?

• A. Arginase
• B. Argininosuccinase
• C. Carbamoyl-phosphate synthase
• D. Ornithine transcarbamylase

Hint:

First, allosteric, mitochondrial step activated by N-acetylglutamate.

Answer 1

The Correct Option is C

Step 1: The urea cycle disposes of ammonia as urea in five steps. The first committed step is the formation of carbamoyl phosphate from ammonia and carbon dioxide, using 2 ATP, catalyzed by carbamoyl phosphate synthase I (CPS-I) in the mitochondria.

Step 2: CPS-I is the rate limiting enzyme of the urea cycle. It is an allosteric enzyme that is activated by N-acetylglutamate, so flux through the whole cycle is controlled at this point.

Step 3: Do not confuse CPS-I with the cytosolic CPS-II, which uses glutamine as the nitrogen donor and works in pyrimidine synthesis, not urea formation.

Step 4: The other enzymes act later and are not rate limiting. Ornithine transcarbamylase makes citrulline, argininosuccinase (argininosuccinate lyase) splits argininosuccinate into arginine and fumarate, and arginase finally cleaves arginine into urea and ornithine.