This drug also acts on the mevalonate
pathway and inhibits farnesyl pyrophosphatase, which is the key enzyme in cholesterol synthesis.
In recent years the Mathematical Biology Group at the University of Reading, in collaboration with colleagues at Syngenta has been developing mathematical models of the mevalonate
pathway - a key regulatory pathway in cholesterol biosynthesis.
MVK mutation causes underactivity of mevalonate
kinase, which leads to increased mevalonic acid (11).
In our group, we have researched that three-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) catalyzes the conversion of HMG-CoA to mevalonate
and is considered the rate-limiting enzyme in the overall pathway of cholesterol biosynthesis (Istvan and Deisenhofer, 2000) and have an important role in PPAR signaling pathway.
Statins inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in the multistep mevalonate
cascade for cholesterol synthesis. Statins are widely used in the prevention of cardiovascular disease by lowering cholesterol. Beyond their cholesterol reduction effect, statins have been shown to have pleiotropic effects.,, Accumulating evidences indicated that the inhibition of the mevalonate
pathway by statins induced ER stress and apoptosis in cancerous and noncancerous cells.,,, In this study, we explored the beneficial effect of simvastatin on ox-LDL-induced ER stress and apoptosis in human vascular endothelial cells.
This enzyme is the rate-limiting step in mevalonate
Isoprenoids and Novel Inhibitors of Mevalonate
We analyzed pregnancies at risk of [beta]-thalassemia and mevalonate
kinase deficiency (MKD).
[4-6] Thyroid hormone has a major effect on the lipoprotein metabolism, which stimulates the hepatic de novo cholesterol synthesis by inducing the 3-hydroxy-methyl-glutaryl-coenzyme A (HMG-CoA) reductase that catalyses the conversion of HMG-CoA to mevalonate
, the first step in the biosynthesis of cholesterol.
Their mechanism was shown to go through inhibition of liver HMG-CoA reductase, influencing cholesterol synthesis by producing mevalonate
and lowering low-density lipoprotein (LDL).
Statin and other chemical inhibitors of the mevalonate
pathway can suppress isoprenylation of Rho proteins  and have been tested in many clinical trials.
The sterols are biosynthesized in plant cells via mevalonate
or isoprenoids route, where SQ is also metabolized.