Q29-20E - Organic Chemistry (Mcmurry)

Question

One of the steps in the biosynthesis of uridine monophosphate is the reaction of aspartate with carbamoyl phosphate to give carbamoyl aspartate followed by cyclization to form dihydroorotate. Propose mechanisms for both steps.

Step-by-Step Solution

Answer

The mechanism to form the dihydroorotate is,

Introduction

The reaction of L-aspartate, bicarbonate, and ammonia (produced from the amide nitrogen of L-glutamine) to generate carbamoyl-phosphate kicks off UMP production. Carbamoyl phosphate synthetase catalyzes the process.

Explanation of Carbamoyl phosphate

Carbamoyl phosphate acyl phosphate is extremely electrophilic, and the phosphate is an excellent leaving group. After being deprotonated by an enzymatic base, the aspartate amine can attack the carbamoyl.

Mechanism to form dihydroorotate

The mechanism is,