| First Author | Li L | Year | 2007 |
| Journal | Arch Biochem Biophys | Volume | 461 |
| Issue | 1 | Pages | 76-84 |
| PubMed ID | 17374357 | Mgi Jnum | J:123348 |
| Mgi Id | MGI:3718141 | Doi | 10.1016/j.abb.2007.02.010 |
| Citation | Li L, et al. (2007) Hepatic cytochrome P450 reductase-null mice reveal a second microsomal reductase for squalene monooxygenase. Arch Biochem Biophys 461(1):76-84 |
| abstractText | Squalene monooxygenase is a microsomal enzyme that catalyzes the conversion of squalene to 2,3(s)-oxidosqualene, the immediate precursor to lanosterol in the cholesterol biosynthesis pathway. Unlike other flavoprotein monooxygenases that obtain electrons directly from NAD(P)H, squalene monooxygenase requires a redox partner, and for many years it has been assumed that NADPH-cytochrome P450 reductase is this requisite redox partner. However, our studies with hepatic cytochrome P450-reductase-null mice have revealed a second microsomal reductase for squalene monooxygenase. Inhibition studies with antibody to P450 reductase indicate that this second reductase supports up to 40% of the monooxygenase activity that is obtained with microsomes from normal mice. Studies carried out with hepatocytes from CPR-null mice demonstrate that this second reductase is active in whole cells and leads to the accumulation of 24-dihydrolanosterol; this lanosterol metabolite also accumulates in the livers of CPR-null mice, indicating that cholesterol synthesis is blocked at lanosterol demethylase, a cytochrome P450. |
