RNF145 The involvement of AMFR and Trc8 has been contested. Phosphorylation Short-term regulation of HMG-CoA reductase is achieved by inhibition by phosphorylation (of Serine 872, in humans). Decades ago it was believed that a cascade of enzymes controls the activity of HMG-CoA reductase: an HMG-CoA reductase kinase was thought to inactivate the enzyme, and the kinase in turn was held to be activated via phosphorylation by HMG-CoA reductase kinase kinase. An excellent review on regulation of the mevalonate pathway by Nobel Laureates Joseph Goldstein and Michael Brown adds specifics: HMG-CoA reductase is phosphorylated and inactivated by an AMP-activated protein kinase, which also phosphorylates and inactivates acetyl-CoA carboxylase, the rate-limiting enzyme of fatty acid biosynthesis. Thus, both pathways utilizing acetyl-CoA for lipid synthesis are inactivated when energy charge is low in the cell, and concentrations of AMP rise. There has been a great deal of research on the identity of upstream kinases that phosphorylate and activate the AMP-activated protein kinase. Fairly recently, LKB1 has been identified as a likely AMP kinase kinase, which appears to involve calcium/calmodulin signaling. This pathway likely transduces signals from leptin, adiponectin, and other signaling molecules. See also Oxidoreductase References Further reading External links Cholesterol Synthesis - has some good regulatory details - the HMG-CoA Reductase Structure in Interactive 3D EC 1.1.1