Electron Transfer Pathways in Cholesterol Synthesis.
Cholesterol synthesis in the endoplasmic reticulum requires electron input at multiple steps and utilizes both NADH and NADPH as the electron source. Four enzymes catalyzing five steps in the pathway require electron input: squalene monooxygenase, lanosterol demethylase, sterol 4α-methyl oxidase, and sterol C5-desaturase. The electron-donor proteins for these enzymes include cytochrome P450 reductase and the cytochrome b5 pathway. Here I review the evidence for electron donor protein requirements with these enzymes, the evidence for additional electron donor pathways, and the effect of deletion of these redox enzymes on cholesterol and lipid metabolism.
Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY, 40536-0596, USA. tporter@email.uky.edu.
Todd D
TD
Porter
D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis*; D015786:Cytochromes b5 / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009243:NAD / Q000378:metabolism*; D010088:Oxidoreductases / Q000378:metabolism; D015398:Signal Transduction; D050603:Squalene Monooxygenase / Q000378:metabolism; D058886:Sterol 14-Demethylase / Q000378:metabolism
D009243:NAD; D015786:Cytochromes b5; D002784:Cholesterol; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase; D050603:Squalene Monooxygenase; C027532:methylsterol monooxygenase; C039306:sterol delta-5 desaturase
CYP51; Cytochrome P450 reductase; Cytochrome b5; Cytochrome b5 reductase; Squalene monooxygenase; Sterol 4α-methyl oxidase; Sterol C5-desaturase