What happens when you inhibit HMG-CoA reductase?
Inhibition of HMG-CoA reductase, a rate-limiting enzyme in hepatic cholesterol synthesis by statins, results in the reduction of intracellular cholesterol content that in turn induces an increase in SREBP-2-mediated hepatic LDL receptor synthesis (Sahebkar and Watts, 2013b) (Chapter 11).
What role does the enzyme reductase play in cholesterol regulation?
HMG CoA reductase produces mevalonate, an important intermediate in the synthesis of cholesterol and essential nonsterol isoprenoids. The reductase is subject to an exorbitant amount of feedback control through multiple mechanisms that are mediated by sterol and nonsterol end-products of mevalonate metabolism.
How does insulin regulate HMG-CoA reductase?
Insulin stimulates HMG-CoA reductase activity likely by increasing the rate of transcription, whereas glucagon acts by opposing this effect. Deficiencies in those hormones that act to increase hepatic HMG-CoA reductase gene expression lead to elevations in serum cholesterol levels.
How does an HMG CoA reductase inhibitor lower serum lipid?
Recently, a new class of lipid-lowering drugs, HMG CoA reductase inhibitors, have been introduced. These drugs act by decreasing liver cholesterol synthesis resulting in up-regulation of LDL receptors, increased clearance of LDL from plasma, and diminution of plasma LDL levels.
What regulates HMG-CoA synthase?
HMG-CoA synthase promoter activity is regulated by insulin or EGF. Luciferase activity in HaCaT keratinocytes transfected with a luciferase reporter construct containing the wild-type HMG-CoA synthase promoter.
Which of the following hormones increases synthesis of cholesterol by regulating the enzyme HMG-CoA reductase?
The insulin or thyroid hormones increases HMG-CoA reductase activity and ultimately cholesterol biosynthesis.
What does HMG-CoA reductase reduce?
HMG-CoA reductase inhibitors reduce total cholesterol, low-density lipoprotein cholesterol, and triglycerides concentrations and increase high-density lipoprotein in the blood.
What is the medical significance of HMG-CoA reductase?
Clinical significance. The medical significance of HMG-CoA reductase has continued to expand beyond its direct role in cholesterol synthesis following the discovery that statins can offer cardiovascular health benefits independent of cholesterol reduction. Statins have been shown to have anti-inflammatory properties,…
How is the activity of the enzyme HMG-CoA regulated?
The activity of the enzyme is regulated by changes in transcription, translation (mechanism unknown) and protein stability.
Are there any statins that inhibit HMG-CoA reductase?
Statins, which inhibit HMG-CoA reductase, the rate limiting step in cholesterol synthesis, are thought to exert much of their LDL-C lowering effect by increasing hepatic availability of LDL receptors. The first statin, lovastatin, was approved by the FDA in 1987.
Which is the enzyme that converts HMG-CoA to mevalonic acid?
HMGCR catalyzes the conversion of HMG-CoA to mevalonic acid, a necessary step in the biosynthesis of cholesterol. Normally in mammalian cells this enzyme is competitively suppressed so that its effect is controlled.