Final answer:
The rate-limiting substrate of De Novo cholesterol synthesis is HMG-CoA, which is reduced to mevalonate by the HMG-CoA reductase enzyme. This enzyme is the primary regulatory point in cholesterol synthesis and is controlled by feedback inhibition and hormone-induced phosphorylation.
Step-by-step explanation:
The rate-limiting substrate of De Novo cholesterol synthesis is HMG-CoA, which is the substrate for the rate-limiting enzyme HMG-CoA reductase. This step is critical as it effectively controls the overall rate of cholesterol synthesis. HMG-CoA reductase catalyzes the reduction of HMG-CoA to mevalonate, a precursor to cholesterol. The synthesis begins with two molecules of acetyl-CoA combining to form acetoacetyl-CoA, followed by the addition of another acetyl-CoA to form HMG-CoA. The regulation of cholesterol biosynthesis occurs mainly at this step, with feedback inhibition being a key control mechanism when there is an excess of cholesterol and its intermediate mevalonate. Moreover, the activity of HMG-CoA reductase is modulated by phosphorylation and dephosphorylation in response to hormones like glucagon and epinephrine.