Question

Glutamine is increased in CSF, blood, and urine. This is due to deficiency of which enzyme?

• A. CPS-I
• B. Arginase
• C. OTC
• D. Argininosuccinate synthetase

Hint:

A proximal urea cycle block raises glutamine - look at the rate-limiting enzyme.

Answer 1

The Correct Option is A

Step 1: Carbamoyl phosphate synthetase I (CPS-I) is a proximal urea cycle enzyme. It makes carbamoyl phosphate from ammonia, ATP, and bicarbonate inside the mitochondria.
Step 2: CPS-I is the rate-limiting (pacemaker) step of the urea cycle and is active only when its allosteric activator N-acetylglutamate is present.
Step 3: When CPS-I is deficient, ammonia cannot enter the urea cycle and accumulates. The body buffers ammonia as glutamine, so glutamine rises in CSF, blood, and urine. Among the listed urea-cycle enzymes, the proximal block at CPS-I best fits this picture, so CPS-I is the answer.