What pathway is HMG-CoA reductase?
mevalonate pathway
HMG-CoA Reductase (or 3-hydroxy-3-methyl-glutaryl-CoA reductase or HMGR) is the rate-controlling enzyme of the mevalonate pathway, responsible for cholesterol and other isoprenoid biosynthesis. HMGR is a transmembrane protein, containing 8 domains, that is anchored in the membrane of the endoplasmic reticulum.
What deactivates HMG-CoA reductase?
HMG-CoA reductase is inactivated by phosphorylation (13). This reaction is catalyzed by a protein kinase family, AMP-activated protein kinases (19), and the inactivated enzyme can be reactivated by phosphatase (20).
How is the activity of HMG-CoA reductase reduced?
Statins inhibit HMG-CoA reductase and reduce cellular cholesterol synthesis [1]. Lower intracellular cholesterol concentrations cause over-expression of the LDL receptor in the plasma membrane of hepatocytes.
What is HMG CoA pathway?
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl-CoA, is an intermediate in the mevalonate and ketogenesis pathways. HMG-CoA is a metabolic intermediate in the metabolism of the branched-chain amino acids, which include leucine, isoleucine, and valine.
How does cholesterol inhibit HMG-CoA reductase?
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.
How do statins inhibit HMG-CoA reductase?
Statins act by inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and thereby reducing cholesterol synthesis. In addition to bonds formed by the HMG-like moiety, statins exhibit different types and numbers of binding interactions in association with structural differences.
What happens if HMG-CoA reductase is inhibited?
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 happens if HMG-CoA reductase activity is inhibited?
Inhibition of HMG-CoA reductase reduces cholesterol biosynthesis in the liver. Synthetic drugs, statins, are commonly used for the treatment of hypercholesterolemia. Due to the side effects of statins, natural HMG-CoA reductase inhibitors of plant origin are needed.
What enzyme does HMG-CoA inhibit?
Also known as statins, HMG-CoA reductase inhibitors work by inhibiting the synthesis of cholesterol in the liver by the enzyme HMG-CoA reductase.
How does inhibition of HMG-CoA reductase cause lowering of cholesterol and LDL levels?
How do HMG-CoA reductase work?
Introduction. Also known as statins, HMG-CoA reductase inhibitors work by inhibiting the synthesis of cholesterol in the liver by the enzyme HMG-CoA reductase.