HMG-CoA reductase

HMG-CoA reductase is the enzyme that converts 3-hydroxy-3-methylglutaryl-CoA into mevalonate, using NADPH. This regulated reaction is the rate-limiting step of the mevalonate pathway.

Mevalonate pathway: A metabolic pathway that converts acetyl-CoA into cholesterol and other isoprenoid compounds. HMG-CoA reductase catalyzes the pathway’s committed, rate-limiting conversion to mevalonate.
Statin: A class of drugs that lowers cholesterol by inhibiting HMG-CoA reductase. Statins compete at the enzyme’s active site and reduce hepatic cholesterol synthesis.
Cholesterol: A sterol molecule used in cell membranes and as a precursor for steroid hormones, bile acids, and vitamin D. The mevalonate pathway supplies the carbon used to make cholesterol.
Konrad Bloch: A biochemist who helped establish the pathway of cholesterol biosynthesis and shared the 1964 Nobel Prize in Physiology or Medicine. His research helped identify the biochemical steps leading from acetate to cholesterol.
HMG-CoA: A metabolic intermediate formed from acetyl-CoA that serves as the substrate for HMG-CoA reductase. The enzyme binds HMG-CoA and reduces it to mevalonate.
Atorvastatin: A synthetic statin prescribed to lower LDL cholesterol and reduce cardiovascular risk. It is a widely used example of therapeutic inhibition of this enzyme.
Acetyl-CoA: A central metabolic molecule that carries acetyl groups into biosynthetic and energy-producing pathways. It supplies the carbon atoms that ultimately reach HMG-CoA and mevalonate.
Feodor Lynen: A biochemist who investigated acetate metabolism and cholesterol biosynthesis and shared the 1964 Nobel Prize in Physiology or Medicine. His work clarified the pathway in which HMG-CoA reductase functions.
Mevalonate: A six-carbon molecule produced from HMG-CoA in the first committed step of sterol and isoprenoid synthesis. It is the direct product of the enzyme’s catalytic reaction.
LDL cholesterol: Cholesterol carried in low-density lipoprotein particles in the blood. Inhibiting the enzyme lowers liver cholesterol and promotes LDL removal from circulation.

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