1. Metabolism of mevalonic acid and early steps in the biosynthesis of cholesterol. The structures and names of the intermediates in the synthetic pathway for mevalonic acid, cholesterol and other isoprenoids are shown in the center, with the names of the enzymes on the left and the metabolites that may be elevated due to a deficiency of mevalonate kinase shown on the right. 3-Hydroxy-3-methylglutaryl-CoA is derived from fatty acid oxidation. The first step of isoprenoid biosynthesis involves peroxisomal 3-hydroxy-3-methylglutaryl-CoA reductase, which reductively decarboxylates the CoA thioester group of the substrate with NADP+ to release carbon dioxide, CoA, and 3-R-mevalonic acid. This enzyme is highly regulated in its activity by phosphorylation and dephosphorylation. Its rate of degradation may be affected by oxygenated sterols. Its synthesis is controlled at the transcriptional level by end products of isoprenoid biosynthesis and in particular by sterols. The reductase reaction is not reversible.
Source: Branched Chain Organic Acidurias, The Online Metabolic and Molecular Bases of Inherited Disease
Citation: Valle D, Beaudet AL, Vogelstein B, Kinzler KW, Antonarakis SE, Ballabio A, Gibson K, Mitchell G. The Online Metabolic and Molecular Bases of Inherited Disease; 2014 Available at: Accessed: January 23, 2018
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