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 does HMG CoA synthase do?
Uniquely among condensing enzymes, 3-hydroxy-3-methylglutaryl (HMG)–CoA synthase (HMGS) catalyzes the formation of a carbon–carbon bond by activating the methyl group of an acetylated cysteine.
How does inhibition of HMG-CoA reductase cause lowering of cholesterol and LDL levels?
HMG-CoA reductase inhibitors lower plasma LDL cholesterol by one or a combination of the following mechanisms: (1) enhanced catabolism by upregulation of hepatic LDL receptors, (2) production of an LDL particle that is a better ligand for the LDL receptor, (3) reduced production of LDL apoB due to either decreased …
Why is HMG-CoA reductase is an ideal target for cholesterol reducing medications?
Normally in mammalian cells this enzyme is competitively suppressed so that its effect is controlled. This enzyme is the target of the widely available cholesterol-lowering drugs known collectively as the statins, which help treat dyslipidemia….HMG-CoA reductase.
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Does cholesterol inhibit HMG-CoA reductase?
Statins. 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.
How statins bind to and inhibit their target HMG-CoA?
Statins act by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme of the mevalonate pathway. 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).
Which enzyme is required for the synthesis of ketone bodies as well as cholesterol?
In eukaryotes, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is a key enzyme that catalyses the synthesis of a precusor of cholesterol as well as non-sterol isoprenoids, mevalonate.
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.
How does atorvastatin lower cholesterol?
Lipitor (atorvastatin) is a cholesterol-lowering medication that belongs to the statin class of drugs. Statins lower cholesterol levels in the blood by blocking 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, an enzyme that’s needed for the liver to produce cholesterol.
How do statins reduce cholesterol?
Statins work by slowing down the production of LDL-cholesterol in the liver, where it’s made. Because the liver isn’t making so much cholesterol, it then takes cholesterol out of your blood to make bile with, so your blood cholesterol levels fall.
Why is atorvastatin used to treat elevated cholesterol values?
Atorvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.
How do statins lower cholesterol?