The Cholesterol reference article from the English Wikipedia on 24-Jul-2004
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Cholesterol

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Cholesterol chemical structure
Cholesterol is a steroid lipid, found in the body tissues (and blood plasma) of vertebrates. It can be found in large concentrations within the liver, spinal cord, and brain. It plays a central role in many biochemical processes, but is best known for causing cardiovascular disease when present in elevated levels.

Table of contents
1 History of the name
2 Physiology
3 Role in disease
4 Cholesteric liquid crystals
5 See also
6 Sources
7 External links

History of the name

The name originates from the Greek chole- (bile) and stereos (solid), as researchers first identified cholesterol in solid form in gallstones.

Physiology

Synthesis

The HMG-CoA reductase pathwayEnlarge

The HMG-CoA reductase pathway

is primarily synthesized from acetyl CoA through the HMG-CoA reductase pathway in the liver (~1 g/day), although other sites include the intestines, adrenal glands and reproductive organs.

Properties

Mostly insoluble in water, it travels in the blood stream in the form of lipoproteins. Initially, it is carried from the intestinal mucosa to the liver in chylomicrons. In the liver it is converted into low-density lipoprotein (LDL) to carries cholesterol to the body cells, while high-density lipoprotein (HDL) carries it back to the liver for excretion.

It is interesting to note that the cholesterol in LDL cholesterol and the cholesterol in HDL cholesterol are identical. The only difference between the two is the carrier molecule (i.e. the lipoprotein).

Regulation

The production is directly regulated by the present cholesterol levels, and a higher intake in food leads to a net decrease in endogenous production. 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). In the presence of cholesterol, SREBP is bound to two other proteins: SCAP (SREBP-cleavage activating protein) and Insig-1. 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 1/2 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 "Sterol Regulatory Element" of a number of genes to stimulate their transcription. Amongst the genes transcribed are the LDL receptor and HMG-CoA reductase. The former scavenges circulating LDL from the bloodstream, while HMG-CoA reductase leads to an increase of endogenous production of cholesterol.

A large part of this mechanism was clarified by Dr Michael S. Brown and Dr Joseph L. Goldstein, who received the Nobel Prize in Physiology or Medicine for their work in 1985.

A study by Ockrene et al showed that there are seasonal variations in cholesterol levels in humans. Although no explanation could be found, it explains why more patients may be diagnosed with elevated cholesterol levels in winter.

Function

Cholesterol is an important component of the membranes of cells, providing stability. It is the major precursor for the synthesis of vitamin D, of the various steroid hormones, including cortisol, cortisone, and aldosterone in the adrenal glands, and of the sex hormones progesterone, estrogen, and testosterone. Further recent research show that cholesterol has an important role for the brain synapses as well as in the immune system.

Excretion

Cholesterol is excreted from the liver in bile; under certain circumstances it can crystallise in the gallbladder to become a major constituent of gallstones, although lecitin and bilirubin gallstones can also occur.

Role in disease

See also the main article hypercholesterolemia

In conditions featuring elevated LDL, cholesterol often forms plaque deposits in the walls of arteries, a condition known as atherosclerosis, which is a major contributor to coronary heart disease and other forms of cardiovascular disease.

The American Heart Association provides a set of guidelines for total (fasting) blood cholesterol levels and risk for heart disease:

Level mg/dL Level mmol/L Interpretation
<200 <5.2 Desirable level corresponding to lower risk for heart disease
200-239 5.2-6.2 Borderline high risk
>240 >6.2 High risk

However, as today's testing methods determine LDL ("bad") and HDL ("good") cholesterol separetely, this simplistic view has become somewhat outdated. The desirable LDL level is considered to be 75-130 mg/dl (1.9-3.3 mmol/L), and a ratio of total cholesterol to HDL—arguably the most useful measure—of less than 5:1 is thought to be healthy.

Cholesteric liquid crystals

Some cholesterol derivatives, (among others simple cholesteric lipids) are known to generate liquid crystalline phase called "cholesteric". The cholesteric phase is in fact a chiral nematic phase. It has ability to change the colour with the change of temperature. Therefore the cholesterol derivatives are commonly used as a temperature sensitive dyes used in liquid crystalline thermometers and temperature sensitive paints.

See also

Sources

External links