Cholesterol

Cholesterol
Identifiers
CAS number 57-88-5 YesY
PubChem 5997
ChemSpider 5775 YesY
UNII 97C5T2UQ7J YesY
KEGG D00040 YesY
ChEBI CHEBI:16113 YesY
ChEMBL CHEMBL112570 YesY
Jmol-3D images Image 1
Properties
Molecular formula C27H46O
Molar mass 386.65 g/mol
Appearance white crystalline powder[2]
Density 1.052 g/cm3
Melting point

148–150 °C[2]

Boiling point

360 °C (decomposes)

water 0.095 mg/L (30 °C)
Solubility soluble in methanol
Hazards
Flash point 209.3 ±12.4°C [1]
 YesY (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

Microscopic appearance of cholesterol crystals in water. Photo taken under polarized light.

Cholesterol, from the fluidity.

In addition to its importance within cells, cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile acids, and vitamin D.[3] Cholesterol is the principal sterol synthesized by animals; in vertebrates it is formed predominantly in the liver. Small quantities are synthesized in other cellular organisms (eukaryotes) such as plants and fungi. It is almost completely absent among prokaryotes (i.e., bacteria).

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”.[4]

Contents

[edit] Physiology

Since cholesterol is essential for all animal life, each cell synthesizes it from simpler molecules, a complex 37-step process which starts with the intracellular protein enzyme atherosclerosis.

For a man 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, primarily located within all the membranes of all the cells of the body. Typical daily dietary intake of additional cholesterol, in the United States, is 200–300 mg.[5]

However, most ingested cholesterol is esterified and esterified cholesterol is poorly absorbed. The body also compensates for any absorption of additional cholesterol by reducing cholesterol synthesis.[6] For these reasons, cholesterol intake in food has little, if any, effect on total body cholesterol content or concentrations of cholesterol in the blood.

Cholesterol is recycled. The liver excretes it in a non-esterified form (via bile) into the digestive tract. Typically about 50% of the excreted cholesterol is reabsorbed by the small bowel back into the bloodstream.

Some plants make cholesterol in very small amounts.[8] When intestinal lining cells absorb phytosterols, in place of cholesterol, they usually excrete the phytosterol molecules back into the GI tract, an important protective mechanism.

[edit] Function

Cholesterol is required to build and maintain [12]

Within the cell membrane, cholesterol also functions in intracellular transport, cell signaling and nerve conduction. Cholesterol is essential for the structure and function of invaginated [14]

Within cells, cholesterol is the precursor molecule in several biochemical pathways. In the liver, cholesterol is converted to bile, which is then stored in the gallbladder. Bile contains bile salts, which solubilize fats in the digestive tract and aid in the intestinal absorption of fat molecules as well as the fat-soluble vitamins, A, D, E, and K. Cholesterol is an important precursor molecule for the synthesis of vitamin D and the steroid hormones, including the adrenal gland hormones cortisol and aldosterone, as well as the sex hormones progesterone, estrogens, and testosterone, and their derivatives.[3]

Some research indicates cholesterol may act as an antioxidant.[15]

[edit] Dietary sources

[18]

From a dietary perspective, cholesterol is not found in significant amounts in plant sources.[24]

Fat-intake also plays a role in blood-cholesterol levels. This effect is thought[[29]

However, the The China Study uses epidemiological evidence to claim that casein raises blood cholesterol even more than the ingested saturated fat or cholesterol.[30]

[edit] Biosynthesis

All animal cells manufacture cholesterol with relative production rates varying by cell type and organ function. About 20–25% of total daily cholesterol production occurs in the statin drugs (HMG-CoA reductase competitive inhibitors).

Mevalonate is then converted to 3-isopentenyl pyrophosphate in three reactions that require [32]

fatty acid metabolism.

[edit] Regulation of cholesterol synthesis

Biosynthesis of cholesterol is directly regulated by the cholesterol levels present, though 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.[35]

[edit] Plasma transport and regulation of absorption

Cholesterol is only slightly soluble in triglycerides and cholesterol esters are carried internally. Phospholipids and cholesterol, being amphipathic, are transported in the surface monolayer of the lipoprotein particle.

In addition to providing a soluble means for transporting cholesterol through the blood, lipoproteins have cell-targeting signals that direct the lipids they carry to certain tissues. For this reason, there are several types of lipoproteins within blood called, in order of increasing density, apolipoproteins, which serve as ligands for specific receptors on cell membranes. In this way, the lipoprotein particles are molecular addresses that determine the start- and endpoints for cholesterol transport.

Chylomicrons, the least dense type of cholesterol transport molecules, contain apolipoprotein E in their shells. Chylomicrons are the transporters that carry fats from the intestine to muscle and other tissues that need fatty acids for energy or fat production. Cholesterol that is not used by muscles remains in more cholesterol-rich chylomicron remnants, which are taken up from here to the bloodstream by the liver.

VLDL molecules are produced by the liver and contain excess triacylglycerol and cholesterol that is not required by the liver for synthesis of bile acids. These molecules contain HTGL, taken up by the LDL receptor on the liver cell surfaces, and the other half continue to lose triacylglycerols in the bloodstream until they form LDL molecules, which have the highest percentage of cholesterol within them.

LDL molecules, therefore, are the major carriers of cholesterol in the blood, and each one contains approximately 1,500 molecules of cholesterol ester. The shell of the LDL molecule contains just one molecule of apolipoprotein B100, which is recognized by the lysosomal acid lipase that hydrolyzes the cholesterol esters. Now within the cell, the cholesterol can be used for membrane biosynthesis or esterified and stored within the cell, so as to not interfere with cell membranes.

Synthesis of the LDL receptor is regulated by [35]

Also, HDL particles are thought to transport cholesterol back to the liver for excretion or to other tissues that use cholesterol to synthesize hormones in a process known as atheromatous disease progression within the arteries.

[edit] Metabolism, recycling and excretion

Cholesterol is susceptible to oxidation and easily forms oxygenated derivatives known as [40]

In biochemical experiments radiolabelled forms of cholesterol, such as tritiated-cholesterol are used. These derivatives undergo degradation upon storage and it is essential to purify cholesterol prior to use. Cholesterol can be purified using small Sephadex LH-20 columns.[41]

Cholesterol is oxidized by the liver into a variety of non-primary source needed]

[edit] Clinical significance

[edit] Hypercholesterolemia

According to the [48]

Conditions with elevated concentrations of oxidized LDL particles, especially “small dense LDL” (sdLDL) particles, are associated with atheroma formation in the walls of arteries, a condition known as atherosclerosis, which is the principal cause of coronary heart disease and other forms of cardiovascular disease. In contrast, HDL particles (especially large HDL) have been identified as a mechanism by which cholesterol and inflammatory mediators can be removed from atheroma. Increased concentrations of HDL correlate with lower rates of atheroma progressions and even regression. A 2007 study pooling data on almost 900,000 subjects in 61 cohorts demonstrated that blood total cholesterol levels have an exponential effect on cardiovascular and total mortality, with the association more pronounced in younger subjects. Still, because cardiovascular disease is relatively rare in the younger population, the impact of high cholesterol on health is still larger in older people.[49]

Elevated levels of the lipoprotein fractions, LDL, IDL and VLDL are regarded as atherogenic (prone to cause atherosclerosis).[51]

Elevated cholesterol levels are treated with a strict diet consisting of low saturated fat, trans fat-free, low cholesterol foods,citation needed]

Multiple human trials using HMG-CoA reductase inhibitors, known as [59]

Level dL Level L Interpretation
< 200 < 5.2 Desirable level corresponding to lower risk for heart disease
200–240 5.2–6.2 Borderline high risk
> 240 > 6.2 High risk

The 1987 report of [61]

However, as today’s testing methods determine LDL (“bad”) and HDL (“good”) cholesterol separately, this simplistic view has become somewhat outdated. The desirable LDL level is considered to be less than 100 mg/dL (2.6 citation needed]

Reference ranges for blood tests, showing usual, as well as optimal, levels of HDL, LDL and total cholesterol in mass and molar concentrations, is found in orange color at right, that is, among the blood constituents with the highest concentration.

Total cholesterol is defined as the sum of HDL, LDL, and VLDL. Usually, only the total, HDL, and triglycerides are measured. For cost reasons, the VLDL is usually estimated as one-fifth of the triglycerides and the LDL is estimated using the Friedewald formula (or a [63]

Given the well-recognized role of cholesterol in cardiovascular disease, some studies have shown an inverse correlation between cholesterol levels and mortality. A 2009 study of patients with acute coronary syndromes found an association of hypercholesterolemia with better mortality outcomes.[66]

The vast majority of doctors and medical scientists consider that there is a link between cholesterol and atherosclerosis as discussed above;[68]

[edit] Hypocholesterolemia

Abnormally low levels of cholesterol are termed hypocholesterolemia. Research into the causes of this state is relatively limited, but some studies suggest a link with depression, cancer, and cerebral hemorrhage. In general, the low cholesterol levels seem to be a consequence, rather than a cause, of an underlying illness.[49]

[edit] Cholesterol testing

The American Heart Association recommends testing cholesterol every five years for people aged 20 years or older.[69]

A blood sample after 12-hour fasting is taken by a doctor, or a home cholesterol-monitoring device is used to determine a lipoprotein profile. This measures total cholesterol, LDL (bad) cholesterol, HDL (good) cholesterol, and triglycerides. It is recommended to test cholesterol at least every five years if a person has total cholesterol of 200 mg/dL or more, or if a man over age 45 or a woman over age 50 has HDL (good) cholesterol less than 40 mg/dL, or there are other risk factors for heart disease and stroke. (In different countries measurements are given in mg/dL or mmol/L; 1 mmol/L is 38.665 mg/dL.)

[edit] Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. [70]

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Statin Pathway edit

[edit] Cholesteric liquid crystals

Some cholesterol derivatives (among other simple cholesteric lipids) are known to generate the thermometers and in temperature-sensitive paints.

[edit] See also

[edit] Additional images

[edit] References

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[edit] External links



Source: Wikipedia

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