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 function of the enzyme HMG-CoA reductase?
HMG-CoA reductase is the rate-limiting enzyme of cholesterol biosynthesis. The expression level of this membrane-bound enzyme is controlled by many factors that in turn regulate cholesterol synthesis and cellular cholesterol homeostasis (reviewed in ).
How do HMG CoA reductase inhibitors lower cholesterol?
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 is HMG-CoA reductase a target for?
Thus, HMG-CoA reductase is a unique molecular target for anti-cancer therapy; it holds a pivotal role in the well-defined MVA pathway, and a specific family of inhibitors is available for immediate application in the cancer clinic. The mevalonate pathway.
Does HMG-CoA reductase make cholesterol?
3-Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase produces mevalonate, an important intermediate in the synthesis of cholesterol and essential nonsterol isoprenoids.
How does HMG-CoA work?
What Are HMG-CoA Reductase Inhibitors and How Do They Work? β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase inhibitors, more popularly known as statins, work by reducing the cholesterol levels in the body. HMG-CoA inhibitors interfere with the ability of the body to build cholesterol from dietary fat.
What does HMG-CoA stand for?
β-Hydroxy β-methylglutaryl-CoA (HMG-CoA), also known as 3-hydroxy-3-methylglutaryl-CoA, is an intermediate in the mevalonate and ketogenesis pathways.
What is the most serious side effect of all HMG CoA reductase inhibitors?
Very rarely, statins can cause life-threatening muscle damage called rhabdomyolysis (rab-doe-my-OL-ih-sis). Rhabdomyolysis can cause severe muscle pain, liver damage, kidney failure and death. The risk of very serious side effects is extremely low, and calculated in a few cases per million people taking statins.
How HMG-CoA is formed?
HMG-CoA is formed by condensation of acetyl-CoA and acetoacetyl-CoA, catalyzed by HMG-CoA synthase. HMG-CoA reductase catalyzes the production of mevalonate from HMG-CoA, in which the HMG-CoA reductase reaction is the rate-limiting step for cholesterol synthesis.
Where is HMG-CoA reductase found?
HMG-CoA reductase is anchored in the membrane of the endoplasmic reticulum, and was long regarded as having seven transmembrane domains, with the active site located in a long carboxyl terminal domain in the cytosol.
Is HMG-CoA reductase only in the liver?
HMG-CoA reductase (HMGR) catalyzes the rate-controlling step in cholesterol production. This enzyme is highly expressed in the liver, where it is subject to extensive hormonal and dietary regulation.
Why should HMG CoA reductase inhibitors be taken before bedtime?
They act by inhibiting the enzyme HMG CoA reductase, which controls synthesis of cholesterol in the liver. Most manufacturers of statins recommend that they are taken at night, on the basis of physiological studies which show that most cholesterol is synthesised when dietary intake is at its lowest.
Why do statins target HMG-CoA reductase?
Statins work by competitively blocking the active site of the first and key rate-limiting enzyme in the mevalonate pathway, HMG-CoA reductase. Inhibition of this site prevents substrate access, thereby blocking the conversion of HMG-CoA to mevalonic acid.
What is cholesterol degradation?
The bacterial degradation of cholesterol has been known to occur by a cholesterol oxidase (cholesterol : oxygen oxidoreductase, EC 1.1. 3.6), the enzyme which catalyses the oxidation of cholesterol to 4-cholesten-3-one, along with the reduction of oxygen to hydrogen peroxide (Smith and Brooks 1976).
Is HDL a cholesterol?
HDL (high-density lipoprotein), or “good” cholesterol, absorbs cholesterol and carries it back to the liver. The liver then flushes it from the body. High levels of HDL cholesterol can lower your risk for heart disease and stroke.
What is cholesterol biosynthesis?
Cholesterol levels in the body come from two sources, dietary intake and biosynthesis. Biosynthesis of cholesterol generally takes place in the endoplasmic reticulum of hepatic cells and begins with acetyl- CoA, which is mainly derived from an oxidation reaction in the mitochondria.
What regulates cholesterol biosynthesis?
Cholesterol synthesis is regulated at the step involving HMG-CoA reductase. The enzyme activity is regulated at the transcriptional level, that is, by changing the rate of synthesis of the mRNA encoding the enzyme. HMG-CoA reductase is regulated by phosphorylation and dephosphorylation also.
What is HMG CoA lyase deficiency?
HMG CoA lyase deficiency is an inherited disorder in which the body cannot process a protein called leucine or make ketones. Ketones are used for energy during periods of fasting.
What are CoA?
(Certificate Of Authenticity) A document that accompanies software which states that it is an original package from the manufacturer. It generally includes a seal with a difficult-to-copy emblem such as a holographic image.
What is the full form of CoA?
The Council of Architecture (COA) has been constituted by the Government of India under the provisions of the Architects Act, 1972, enacted by the Parliament of India, which came into force on 1st September, 1972.
What does HMG stand for medical?
Menotropin (also called human menopausal gonadotropin or hMG) is a hormonally active medication for the treatment of fertility disturbances. Frequently the plural is used as the medication is a mixture of gonadotropins. Menotropins are extracted from the urine of postmenopausal women.
Do statins age you faster?
However, it is not the only mechanism that has been shown to be, and which ones are causal has not really been determined. Interestingly, another study recently reported that statins could slow aging, as they were found to be associated with longer telomere length.
Which cholesterol drug is safest?
Still, all in all, the statins are the safest and best tolerated of all cholesterol-lowering medications.
What is the best cholesterol medication with the least side effects?
In the analysis of 135 previous studies, which included nearly 250,000 people combined, researchers found that the drugs simvastatin (Zocor) and pravastatin (Pravachol) had the fewest side effects in this class of medications. They also found that lower doses produced fewer side effects in general.
How many carbons are in HMG-CoA?
In the first, also called the mevalonate pathway, three molecules of acetyl-coenzyme A (CoA) are successively condensed by the action of acetyl-CoA acetyltransferase and cytosolic 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase to form HMG-CoA, which is then reduced with the loss of CoA, generating mevalonate, a six-.