Chapter 24, Problem 8P

Interpretation Introduction

Interpretation:

Tracing each of the carbon atoms of mevalonate through the synthesis of cholesterol, the source (that is the position in the mevalonate structure) of each carbon in the final structure should be determined.

Concept Introduction:

The first step of cholesterol biosynthesis is Claisen condensation of two molecules of acetyl-CoA to form acetoacetyl CoA which is catalyzed by ß ketothiolase. Next acetyl-CoA and acetoacetyl-CoA combine to form HMG-CoA which is catalyzed by HMG-CoA synthase. This HMG-CoA undergoes two NADPH dependent reductions to form 3R mevalonate. This is the rate limiting step of cholesterol biosynthesis. This mevalonate is converted to squalene after various steps in between. Squalene is then converted to squalene-2,3-epoxide and then to lanosterol. This lanosterol is finally converted to cholesterol after another twenty steps.