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The main isoform (isoform 1) of HMG-CoA reductase in humans is 888 amino acids long. It is a polytopic transmembrane protein (meaning it possesses many alpha helical transmembrane segments).
The following reaction involves the joining of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA, a process catalyzed by HMG-CoA synthase. [8] In the final step of mevalonate biosynthesis, HMG-CoA reductase, an NADPH-dependent oxidoreductase, catalyzes the conversion of HMG-CoA into mevalonate, which is the primary regulatory point in this pathway.
The mevalonate pathway of eukaryotes, archaea, and eubacteria all begin the same way. The sole carbon feed stock of the pathway is acetyl-CoA. The first step condenses two acetyl-CoA molecules to yield acetoacetyl-CoA. This is followed by a second condensation to form HMG-CoA (3-hydroxy-3- methyl-glutaryl-CoA). Reduction of HMG-CoA yields (R ...
This abnormal processing theoretically triggers the generation of antibodies targeting the HMG-CoA reductase protein resulting in SAAM. [1] Another theory postulates that the configuration of the HMG-CoA reductase protein may change when statin medications bind to it causing the protein to expose certain antigens that the immune system is not ...
Because statins are similar in structure to HMG-CoA on a molecular level, they will fit into the enzyme's active site and compete with the native substrate (HMG-CoA). This competition reduces the rate by which HMG-CoA reductase is able to produce mevalonate, the next molecule in the cascade that eventually produces cholesterol.
Statins (HMG-CoA reductase inhibitors) are particularly well suited for lowering LDL, the cholesterol with the strongest links to vascular diseases. In studies using standard doses, statins have been found to lower LDL-C by 18% to 55%, depending on the specific statin being used.
In archaea, HMG-CoA reductase is a cytoplasmic enzyme involved in the biosynthesis of the isoprenoids side chains of lipids. [3] Class I HMG-CoA reductases consist of an N-terminal membrane domain (lacking in archaeal enzymes), and a C-terminal catalytic region. The catalytic region can be subdivided into three domains: an N-domain (N-terminal ...
The mevalonate pathway (MVA pathway or HMG-CoA reductase pathway) and the MEP pathway are metabolic pathways for the biosynthesis of isoprenoid precursors: IPP and DMAPP. . Whereas plants use both MVA and MEP pathway, most organisms only use one of the pathways for the biosynthesis of isoprenoid precurs