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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.
HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, official symbol HMGCR) is the rate-controlling enzyme (NADH-dependent, EC 1.1.1.88; NADPH-dependent, EC 1.1.1.34) of the mevalonate pathway, the metabolic pathway that produces cholesterol and other isoprenoids.
Mevastatin (compactin, ML-236B) is a hypolipidemic agent that belongs to the statins class.. It was isolated from the mold Penicillium citrinum by Akira Endo in the 1970s, and he identified it as a HMG-CoA reductase inhibitor, [1] i.e., a statin.
Thus, the presence of anti-HMG CoA reductase antibodies in someone who uses a statin and has myopathy strongly supports the diagnosis. [3] CK levels increase to 10-100 times above normal (2000–20,000 IU/L) in more than 90% of cases.
The discovery of HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, called statins, was a breakthrough in the prevention of hypercholesterolemia and related diseases. Hypercholesterolemia is considered to be one of the major risk factors for atherosclerosis which often leads to cardiovascular , cerebrovascular and peripheral ...
Most efficacious in lowering LDL-C levels, statins block the action of HMG-CoA reductase through competitive inhibition. [18] HMG-CoA reductase, an enzyme found in hepatocytes, is responsible for the conversion of HMG-CoA to mevalonic acid for cholesterol biosynthesis. Inhibition of this enzyme reduces the synthesis and thus, availability of ...
As a reversible competitive inhibitor, pravastatin sterically hinders the action of HMG-CoA reductase by occupying the active site of the enzyme. Taking place primarily in the liver, this enzyme is responsible for the conversion of HMG-CoA to mevalonate in the rate-limiting step of the biosynthetic pathway for cholesterol. Pravastatin also ...
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.