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Lecture 10. Cholesterol Synthesis. Bloch: Fate of Labeled CH 3 COOH. Cholesterol is made of 2 C units. Path from Acetate to Sterol. Synthesis of Mevalonic Acid. Acetoacetyl CoA. HMG-CoA synthase. (distinct from mitonchondrial). (In cytosol). Ketone Body Formation: Acetoacetate.
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Lecture 10 Cholesterol Synthesis
Bloch: Fate of Labeled CH3COOH Cholesterol is made of 2 C units.
Synthesis of Mevalonic Acid Acetoacetyl CoA HMG-CoA synthase (distinct from mitonchondrial) (In cytosol)
Synthesis of Mevalonate: HMG-CoA reductase • An integral membrane protein of the ER • Major point of regulation of cholesterol synthesis • Suppressed by uptake of LDL cholesterol
Drugs that inhibit HMG-CoA reductase (Atorvastatin)
CH 3 CH CH CH OH 2 2 2 CH 3 CH CH CH 2 2 2 Synthesis of Isopentenyl Pyrophosphate O C C HO OH 3 individual steps 3 ATP 3 ADP O O C C O P O HO O O O P O O P O O O
CH 3 O C CH C CH CH P P O 2 2 2 O O O P O O CO 2 CH P 3 i CH C CH CH O P P Isopentenyl-PP 2 2 2 CH 3 H C C CH CH O P P Dimethylallyl-PP 3 2 Synthesis of Isopentyl Pyrophosphate Isoprenyl-PPs
Isoprenyl Condensations Enzyme:prenyl transferase
Isoprenyl Condensations Enzyme:prenyl transferase
Squalene Synthesis and Ring Closure (Complicated mechanism)
Squalene Synthesis and Ring Closure (19 steps) (Require NADPH and O2)