Cholesterol

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For the journal, see Cholesterol (journal).

Cholesterol
 Names

IUPAC name

Cholest-5-en-3β-ol

Preferred IUPAC name

(1R,3aS,3bS,7S,9aR,9bS,11aR)-9a,11a-Dimethyl-1-[(2R)-6-methylheptan-2-

yl]-2,3,3a,3b,4,6,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-

cyclopenta[a]phenanthren-7-ol

Other names

Cholesterin, Cholesteryl alcohol[1]

Identifiers

57-88-5 
CAS Number

3D model Interactive image

(JSmol)

ChEBI CHEBI:16113 

ChEMBL ChEMBL112570 
ChemSpider 5775 

ECHA 100.000.321 

InfoCard

IUPHAR/BPS 2718

KEGG D00040 

PubChem CID 5997

UNII 97C5T2UQ7J 

CompTox DTXSID3022401 

Dashboard (EP

A)

show

InChI

show

SMILES

Properties

Chemical C27H46O

formula

Molar mass 386.65 g/mol

Appearance white crystalline powder[2]

Density 1.052 g/cm3

Melting point 148 to 150 °C (298 to 302 °F; 421 to 423 K)[2]

Boiling point 360 °C (680 °F; 633 K) (decomposes)

Solubility in 0.095 mg/L (30 °C)[1]

water

Solubility soluble

in acetone, benzene, chloroform, ethanol, ether, hexane, is

opropyl myristate, methanol

Magnetic -284.2·10−6 cm3/mol

susceptibility (
 χ)

Hazards

Flash point 209.3 ±12.4 °C

Except where otherwise noted, data are given for materials in their standard

state (at 25 °C [77 °F], 100 kPa).

 verify (what is   ?)

Infobox references

Types of fats in food

 Saturated fat

 Unsaturated fat

o Monounsaturated fat

 ω−7

 ω−9

o Polyunsaturated fat

 ω−3

 ω−6

o Trans fat

o Interesterified fat

See also

 Fatty acid

 Essential fatty acid

 Conditionally essential fatty acid

 Triglyceride

 Cholesterol

 v
 t
 e

Cholesterol is any of a class of certain organic molecules called lipids. It is

a sterol (or modified steroid),  a type of lipid.  Cholesterol is biosynthesized by all
[3] [1]

animal cells and is an essential structural component of animal cell membranes. When

chemically isolated, it is a yellowish crystalline solid.
Cholesterol also serves as a precursor for the biosynthesis of steroid hormones, bile
acid  and vitamin D. Cholesterol is the principal sterol synthesized by all animals.
[4]
 In vertebrates, hepatic cells typically produce the greatest amounts. It is absent
among prokaryotes (bacteria and archaea), although there are some exceptions, such
as Mycoplasma, which require cholesterol for growth. [5]

François Poulletier de la Salle first identified cholesterol in solid form in gallstones in

1769. However, it was not until 1815 that chemist Michel Eugène Chevreul named the
compound "cholesterine". [6][7]

Contents

 1Etymology
 2Physiology
o 2.1Function in cells
 2.1.1Membranes
 2.1.2Substrate presentation
 2.1.3Signaling
 2.1.4Chemical precursor
o 2.2Metabolism
 3Biosynthesis and regulation
o 3.1Biosynthesis
o 3.2Regulation of cholesterol synthesis
o 3.3Plasma transport and regulation of absorption
o 3.4Metabolism, recycling and excretion
 4Dietary sources
o 4.1Medical guidelines and recommendations
 5Clinical significance
o 5.1Hypercholesterolemia
o 5.2Hypocholesterolemia
o 5.3Cholesterol testing
 6Interactive pathway map
 7Cholesteric liquid crystals
 8Stereoisomers
 9Additional images
 10See also
 11References
 12External links

Etymology[edit]
The word "cholesterol" comes from the Ancient Greek chole- (bile) and stereos (solid),
followed by the chemical suffix -ol for an alcohol.

Physiology[edit]
Cholesterol is essential for all animal life, with each cell capable of synthesizing it by
way of a complex 37-step process. This begins with the mevalonate or HMG-CoA
reductase pathway, the target of statin drugs, which encompasses the first 18 steps.
This is followed by 19 additional steps to convert the resulting lanosterol into
cholesterol.
A human male weighing 68 kg (150 lb) normally synthesizes about 1 gram (1,000 mg)
of cholesterol per day, and his body contains about 35 g, mostly contained within the
cell membranes. Typical daily cholesterol dietary intake for a man in the United States is
307 mg. [8]

Most ingested cholesterol is esterified, which causes it to be poorly absorbed by the gut.
The body also compensates for absorption of ingested cholesterol by reducing its own
cholesterol synthesis.  For these reasons, cholesterol in food, seven to ten hours after
[9]

ingestion, has little, if any effect on concentrations of cholesterol in the blood.

 However, during the first seven hours after ingestion of cholesterol, as absorbed fats
[10]

are being distributed around the body within extracellular water by the
various lipoproteins (which transport all fats in the water outside cells), the
concentrations increase. [11]

Plants make cholesterol in very small amounts.  In larger quantities they
[12]

produce phytosterols, chemically similar substances which can compete with

cholesterol for reabsorption in the intestinal tract, thus potentially reducing cholesterol
reabsorption.  When intestinal lining cells absorb phytosterols, in place of cholesterol,
[13]

they usually excrete the phytosterol molecules back into the GI tract, an important
protective mechanism. The intake of naturally occurring phytosterols, which encompass
plant sterols and stanols, ranges between ≈200–300 mg/day depending on eating
habits.  Specially designed vegetarian experimental diets have been produced yielding
[14]

upwards of 700 mg/day. [15]

Function in cells[edit]
Membranes[edit]

Cholesterol composes about 30% of all animal cell membranes. It is required to build

and maintain membranes and modulates membrane fluidity over the range of
physiological temperatures. The hydroxyl group of each cholesterol molecule interacts
with water molecules surrounding the membrane, as do the polar heads of
the membrane phospholipids and sphingolipids, while the bulky steroid and
the hydrocarbon chain are embedded in the membrane, alongside the nonpolar fatty-
acid chain of the other lipids. Through the interaction with the phospholipid fatty-acid
chains, cholesterol increases membrane packing, which both alters membrane
fluidity  and maintains membrane integrity so that animal cells do not need to build cell
[16]

walls (like plants and most bacteria). The membrane remains stable and durable without
being rigid, allowing animal cells to change shape and animals to move.
The structure of the tetracyclic ring of cholesterol contributes to the fluidity of the cell
membrane, as the molecule is in a trans conformation making all but the side chain of
cholesterol rigid and planar.  In this structural role, cholesterol also reduces the
[17]

permeability of the plasma membrane to neutral solutes,  hydrogen ions,

[18]

and sodium ions. [19]

Substrate presentation[edit]
Cholesterol regulates the biological process of substrate presentation and the enzymes
that use substrate presentation as a mechanism of their activation. (PLD2) is a well-
defined example of an enzyme activated by substrate presentation.  The enzyme [20]

is palmitoylated causing the enzyme to traffic to cholesterol dependent lipid domains

sometimes called "lipid rafts". The substrate of phospholipase
D is phosphatidylcholine (PC) which is unsaturated and is of low abundance in lipid
rafts. PC localizes to the disordered region of the cell along with the polyunsaturated
lipid phosphatidylinositol 4,5-bisphosphate (PIP2). PLD2 has a PIP2 binding domain.
When PIP2 concentration in the membrane increases, PLD2 leaves the cholesterol-
dependent domains and binds to PIP2 where it then gains access to its substrate PC
and commences catalysis based on substrate presentation.

Substrate presentation; PLD (blue oval) is sequestered into cholesterol-dependent lipid domains (green lipids)
by palmitoylation. PLD also binds PIP2(red hexagon) domains (grey shading) located in the disordered region of the cell with
phosphatidylcholine (PC). When cholesterol decreases or PIP2 increases in the cell, PLD translocates to PIP2 where it is
exposed to and hydrolizes PC to phosphatidic acid (red spherical lipid).

Signaling[edit]

Cholesterol is also implicated in cell signaling processes, assisting in the formation

of lipid rafts in the plasma membrane, which brings receptor proteins in close proximity
with high concentrations of second messenger molecules.  In multiple layers, [21]

cholesterol and phospholipids, both electrical insulators, can facilitate speed of

transmission of electrical impulses along nerve tissue. For many neuron fibers,
a myelin sheath, rich in cholesterol since it is derived from compacted layers
of Schwann cell membrane, provides insulation for more efficient conduction of
impulses.  Demyelination (loss of some of these Schwann cells) is believed to be part
[22]

of the basis for multiple sclerosis.

Cholesterol binds to and affects the gating of a number of ion channels such as
the nicotinic acetylcholine receptor, GABA  receptor, and the inward-rectifier potassium
A

channel.  Cholesterol also activates the estrogen-related receptor alpha (ERRα), and

[23]

may be the endogenous ligand for the receptor.  The constitutively active nature of

[24][25]

the receptor may be explained by the fact that cholesterol is ubiquitous in the body.
 Inhibition of ERRα signaling by reduction of cholesterol production has been identified
[25]

as a key mediator of the effects of statins and bisphosphonates on bone, muscle,

and macrophages.  On the basis of these findings, it has been suggested that the
[24][25]

ERRα should be de-orphanized and classified as a receptor for cholesterol. [24][25]

Chemical precursor[edit]
Within cells, cholesterol is also a precursor molecule for several biochemical pathways.
For example, it is the precursor molecule for the synthesis of vitamin D in the calcium
metabolism and all steroid hormones, including the adrenal
gland hormones cortisol and aldosterone, as well as the sex
hormones progesterone, estrogens, and testosterone, and their derivatives. [4][26]

Metabolism[edit]
Cholesterol is recycled in the body. The liver excretes cholesterol into biliary fluids,
which are then stored in the gallbladder, which then excretes them in a non-
esterified form (via bile) into the digestive tract. Typically, about 50% of the excreted
cholesterol is reabsorbed by the small intestine back into the bloodstream. [27]

Biosynthesis and regulation[edit]

Biosynthesis[edit]
All animal cells (exceptions exist within the invertebrates) manufacture cholesterol, for
both membrane structure and other uses, with relative production rates varying by cell
type and organ function. About 80% of total daily cholesterol production occurs in
the liver and the intestines;  other sites of higher synthesis rates include the brain,
[28]

the adrenal glands, and the reproductive organs.

Synthesis within the body starts with the mevalonate pathway where two molecules
of acetyl CoA condense to form acetoacetyl-CoA. This is followed by a second
condensation between acetyl CoA and acetoacetyl-CoA to form 3-hydroxy-3-
methylglutaryl CoA (HMG-CoA). [29]

This molecule is then reduced to mevalonate by the enzyme HMG-CoA reductase.

Production of mevalonate is the rate-limiting and irreversible step in cholesterol
synthesis and is the site of action for statins (a class of cholesterol-lowering drugs).
Mevalonate is finally converted to isopentenyl pyrophosphate (IPP) through two
phosphorylation steps and one decarboxylation step that requires ATP.

Three molecules of isopentenyl pyrophosphate condense to form farnesyl

pyrophosphate through the action of geranyl transferase.
Two molecules of farnesyl pyrophosphate then condense to form squalene by the action
of squalene synthase in the endoplasmic reticulum.
[29]