Regulation of cholesterol synthesis

Regulation of cholesterol synthesis

Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though the homeostatic mechanisms involved are only partly understood. A higher intake from food leads to a net decrease in endogenous production, whereas lower intake from food has the opposite effect. The main regulatory mechanism is the sensing of intracellular cholesterol in the endoplasmic reticulum by the protein SREBP (sterol regulatory element-binding protein 1 and 2).[22] In the presence of cholesterol, SREBP is bound to two other proteins: SCAP (SREBP-cleavage-activating protein) and Insig1. When cholesterol levels fall, Insig-1 dissociates from the SREBP-SCAP complex, allowing the complex to migrate to the Golgi apparatus, where SREBP is cleaved by S1P and S2P (site-1 and -2 protease), two enzymes that are activated by SCAP when cholesterol levels are low. The cleaved SREBP then migrates to the nucleus and acts as a transcription factor to bind to the SRE (sterol regulatory element), which stimulates the transcription of many genes. Among these are the low-density lipoprotein (LDL) receptor and HMG-CoA reductase. The former scavenges circulating LDL from the bloodstream, whereas HMG-CoA reductase leads to an increase of endogenous production of cholesterol.[23] A large part of this signaling pathway was clarified by Dr. Michael S. Brown and Dr. Joseph L. Goldstein in the 1970s. In 1985, they received the Nobel Prize in Physiology or Medicine for their work. Their subsequent work shows how the SREBP pathway regulates expression of many genes that control lipid formation and metabolism and body fuel allocation.

Cholesterol synthesis can be turned off when cholesterol levels are high, as well. HMG CoA reductase contains both a cytosolic domain (responsible for its catalytic function) and a membrane domain. The membrane domain functions to sense signals for its degradation. Increasing concentrations of cholesterol (and other sterols) cause a change in this domain's oligomerization state, which makes it more susceptible to destruction by the proteosome. This enzyme's activity can also be reduced by phosphorylation by an AMP-activated protein kinase. Because this kinase is activated by AMP, which is produced when ATP is hydrolyzed, it follows that cholesterol synthesis is halted when ATP levels are low.[24]

Cholesterol

Here we present you the newest information of the Cholesterol. We provide you the meaning of the Cholesterol and how to prevent this Cholesterol that come to our body.


Cholesterol is a waxy steroid of fat that is manufactured in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals.[2] It is an essential structural component of mammalian cell membranes. It is required to establish proper membrane permeability and fluidity. In addition cholesterol is an important component for the manufacture of bile acids, steroid hormones, and Vitamin D. Cholesterol is the principal sterol synthesized by animals; however, small quantities can be synthesized in eukaryotes such as plants and fungi. It is almost completely absent among prokaryotes including bacteria.[3] Although cholesterol is important and necessary for mammals, high levels of cholesterol in the blood can damage arteries and are potentially linked to diseases such as those associated with the cardiovascular system (heart disease).[4]

The name cholesterol originates from the Greek chole- (bile) and stereos (solid), and the chemical suffix -ol for an alcohol. François Poulletier de la Salle first identified cholesterol in solid form in gallstones, in 1769. However, it was only in 1815 that chemist Eugène Chevreul named the compound "cholesterine".[5]
Contents
[hide]

* 1 Physiology
o 1.1 Function
o 1.2 Dietary sources
o 1.3 Biosynthesis
o 1.4 Regulation of cholesterol synthesis
o 1.5 Plasma transport and regulation of absorption
o 1.6 Metabolism, recycling and excretion
* 2 Significance
o 2.1 Hypercholesterolemia
o 2.2 Hypocholesterolemia
o 2.3 Cholesterol testing
* 3 Interactive pathway map
* 4 Cholesteric liquid crystals
* 5 See also
* 6 Additional images
* 7 References
* 8 External links

[edit] Physiology

Since cholesterol is essential for all animal life, it is primarily synthesized from simpler substances within the body. However, high levels in blood circulation, depending on how it is transported within lipoproteins, are strongly associated with progression of atherosclerosis. For a person of about 68 kg (150 pounds), typical total body cholesterol synthesis is about 1 g (1,000 mg) per day, and total body content is about 35 g. Typical daily additional dietary intake in the United States is 200–300 mg.[citation needed] The body compensates for cholesterol intake by reducing the amount synthesized.

Cholesterol is recycled. It is excreted by the liver via the bile into the digestive tract. Typically about 50% of the excreted cholesterol is reabsorbed by the small bowel back into the bloodstream. Phytosterols can compete with cholesterol reabsorption in the intestinal tract, thus reducing cholesterol reabsorption.[6]