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Item No. 14944

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HMG-CoA reductase (HMGR) is a highly regulated enzyme found on the endoplasmic reticulum (ER) membrane. It is bound to the ER membrane by a multi-pass 339 amino acid N-terminal transmembrane domain while the carboxy terminal catalytic region projects into the cytosol.1,2 HMGR is controlled by feedback regulation from sterols and non-sterol metabolites derived from mevalonate.2,3,4 Binding of cholesterol derived from internalized LDL receptors suppresses HMGR. The enzyme is responsible for catalyzing the rate-limiting step in cholesterol biosynthesis. Mevalonate, which is converted to isopentenyl pyrophosphate, is the building block for cholesterol and non-sterol isoprenoids. The four-electron reduction of HMG-CoA catalyzed by HMGR to form mevalonate is the committed step in the biosynthesis of sterols and isoprenoids.5 Potent inhibitors of HMGR, collectively called statins, are effective in lowering mortality due to hypercholesterolemia by lowering serum cholesterol levels.6
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1. Crystal structure of the catalytic portion of human HMG-
2. Human 3-
3. Multivalent feedback regulation of HMG CoA reductase, a control mechanism coordinating isoprenoid synthesis and cell growth. J. Lipid Res. 21(5), 505-517 (1980).
4. Accelerated degradation of HMG CoA reductase mediated by binding of insig-
5. Structural mechanism for statin inhibition of HMG-
6. Safety of statins. Curr. Opin. Lipidol. 19(6), 558-562 (2008).