BCH2022 Final: Cholesterol Synthesis
25 May 2018
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Cholesterol Synthesis
• Occurs in liver
o Enzymes located in cytosol
o Small amount in small intestine
1. Condensation of two molecules of acetyl CoA to form acetoacetyl CoA
a. Catalyzed by acetyl-CoA acetyltransferase (thiolase)
b. Cofactor: NADPH
• Regulated by enzyme: Hydroxymethylglutaryl-coenzyme A (HMG-CoA)
o Formed from acetoacetyl CoA – catalysed by HMG-CoA synthase
o Inhibited by cholesterol
o Cholesterol repress transcription of HMG-CoA reductase by Sterol
Regulatory Element Binding Protein (SREBP)
o Insulin or thyroid hormone increases HMG-CoA reductase ativity
▪ Glucagon decreases it
o HMG-CoA also intermediate for synthesis of ketone bodies
▪ Enzymes for ketone bodies are located in mitochondrial matrix
• HMG-CoA Reductase
o Catalyses production of mevalonate from HMG-CoA
o Cofactor: NADPH – acts as reductant
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