Question

In biosynthesis of cholesterol, A. 3 -hydroxy-3-methyl glutaryl CoA (HMG CoA) is synthesized by mitochondrial HMG CoA synthase. B. HMG CoA reductase catalyzes the rate-limiting step. C. the conversion of mevalonic acid to farnesyl pyrophosphate proceeds via condensation of three molecules of mevalonic acid. D. condensation of two farnesyl pyrophosphates to form squalene is freely reversible. E. conversion of squalene to lanosterol is initiated by formation of the fused ring system, followed by addition of oxygen.

Short answer

Short Answer: Cholesterol biosynthesis begins with the formation of HMG CoA from acetyl-CoA and acetoacetyl-CoA by HMG CoA synthase. The rate-limiting step is the conversion of HMG CoA to mevalonic acid by HMG CoA reductase. Mevalonic acid is then transformed into farnesyl pyrophosphate through a series of enzymatic reactions. Two molecules of farnesyl pyrophosphate condense to form squalene, which undergoes conversion to lanosterol. Lanosterol is further modified to ultimately produce cholesterol.

Step-by-step solution

1. Synthesis of 3-hydroxy-3-methyl glutaryl CoA (HMG CoA) by mitochondrial HMG CoA synthase

Mitochondrial HMG CoA synthase is an enzyme involved in the early stages of cholesterol biosynthesis. This enzyme catalyzes the reaction that combines acetyl-CoA and acetoacetyl-CoA to form 3-hydroxy-3-methyl glutaryl CoA (HMG CoA). This step is essential for the production of mevalonic acid, which is a precursor to cholesterol.

2. Role of HMG CoA reductase in cholesterol biosynthesis

HMG CoA reductase is a key enzyme in cholesterol biosynthesis, as it catalyzes the rate-limiting step of the process. It converts HMG CoA to mevalonic acid by reducing the carbonyl group at position three of the HMG CoA molecule, using two molecules of NADPH as the reducing agent.

3. Conversion of mevalonic acid to farnesyl pyrophosphate

Mevalonic acid is converted to farnesyl pyrophosphate through a series of enzymatic reactions. This process begins with the condensation of three molecules of mevalonic acid. Each mevalonic acid molecule is first phosphorylated by mevalonate kinase, and then further phosphorylated by phosphomevalonate kinase. Next, mevalonate diphosphate decarboxylase catalyzes the elimination of a carbon atom as CO2, leading to the formation of isopentenyl pyrophosphate (IPP). Finally, IPP is sequentially condensed with two other IPP molecules to form farnesyl pyrophosphate.

4. Condensation of two farnesyl pyrophosphates to form squalene

Squalene, another intermediate in the cholesterol biosynthesis pathway, is formed by the condensation of two molecules of farnesyl pyrophosphate. This reaction is catalyzed by the enzyme squalene synthase. The condensation of farnesyl pyrophosphates to form squalene is freely reversible, allowing for the regulation of squalene levels in the cell.

5. Conversion of squalene to lanosterol

The conversion of squalene to lanosterol marks the beginning of the formation of the sterol nucleus in cholesterol biosynthesis. This step is initiated by the enzyme squalene epoxidase, which adds an oxygen atom to the squalene molecule, forming an epoxide intermediate. Then, the enzyme lanosterol synthase catalyzes the cyclization of the linear squalene molecule into the fused ring system of lanosterol. This transformation involves the formation of three new carbon-carbon bonds, resulting in the formation of the characteristic four-ring structure of sterols. Lanosterol then undergoes further modifications to eventually yield cholesterol.