Which enzyme catalyzes the committed, rate-limiting step of pyrimidine de novo synthesis, and which two substrates does it combine?

• A Dihydroorotase — combines dihydroorotate with PRPP
• B Orotate phosphoribosyltransferase — combines orotate + PRPP to form OMP
• C Carbamoyl phosphate synthetase II (CPS II) — combines glutamine + CO2 + 2 ATP to form carbamoyl phosphate ✓
• D UMP synthase — combines orotic acid + ribose-5-phosphate

Explanation

The committed rate-limiting step of pyrimidine de novo synthesis is catalyzed by carbamoyl phosphate synthetase II (CPS II), a cytosolic enzyme (distinct from mitochondrial CPS I used in the urea cycle). CPS II uses glutamine as the nitrogen donor and incorporates CO2 with 2 ATP to form carbamoyl phosphate; this is then combined with aspartate by ATCase to form carbamoyl aspartate. CPS II activity is inhibited by UMP (feedback) and activated by PRPP. In humans, CPS II, ATCase, and dihydroorotase activities reside on a single trifunctional enzyme (CAD).

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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