Cholesterol
Introduction
Cholesterol from
the Ancient Greek chole (bile) and stereos (solid),
followed by the chemical suffix -ol for
an alcohol is an organic molecule. Cholesterol is biosynthesized
by all animal cells and is an essential structural component of animal cell
membranes. It is a complex monohydric secondary alcohol of
the sterol class. With fatty acids it forms waxes.
Chemistry
and Properties
It is
a sterol (or modified steroid), a type of lipid.
It is a stable white, crystalline substance, insoluble in water but readily
soluble in chloroform, ether, alcohol and other fat-solvents. The crystals have
a rhombic or rectangular shape, with one corner broken off.
Distribution
The distribution of
cholesterol is as follows-
(1) It is present in
all cells-both in the cell membrane and cytoplasm. It is a part of the element
constant
(2) All body fluids
contain cholesterol excepting cerebrospinal fluid (CSF) in which the amount is
negligible.
(3) It may exist in the
Free State as well as in the form of esters, but these two forms are not
equally distributed everywhere. In bile it is present only in the free form.
(4) Brain contains 17% of it and it is mainly
in free form and suprarenal glands contain the largest amount.
(5) Blood cholesterol
Normal blood cholesterol varies between 150-200 mg per 100 ml which is equally
distributed between plasma and corpuscles. But in the corpuscles it is present
chiefly in the free form, while in the plasma the major part remains as esters.
(6) The free
cholesterol content of a tissue is characteristic and normally remains very
constant but the cholesterol esters may vary in amount.
(7) The distribution of
cholesterol in different types of muscles is directly proportional to their
degree of activity. The cardiac and smooth muscles have more cholesterol
content than the voluntary muscles. Moreover, the amount of cholesterol in any
tissue is roughly proportional to their degree of activity.
(8) Cholesterol and
phospholipids always remain together. Moreover, there appears to be a definite
ratio between phospholipids and cholesterol for each tissue.
Synthesis
of cholesterol
The sequence of
reactions in the path of cholesterol synthesis is given below-
1. Activation of
acetate to acetyl CoA.
2. Condensation of two
acetyl CoA molecules to form acetoacetyl CoA.
3. Formation of HMG
CoA.
4. Formation of mevalonic
acid.
5. Mevalonic acid is
phosphorylated by ATP to form 3-diphosphomevalonic acid.
6. The
diphosphomevalonic acid after losing CO and H₂O gives rise to isopentenyl
pyrophosphate.
7. The above compound isomerizes
to form 3-3-dimethylallyl pyrophosphate which combines with isopentenyl
pyrophosphate to give geranyl pyrophosphate.
8. Another molecule of
isopentenyl pyrophosphate combines with geranyl pyrophosphate to form farnesyl
pyrophosphate.
9. Two molecules of
farnesyl pyrophosphate combine to forms qualene.
10. An oxidocyclase
converts squalene to lanosterol.
Absorption
and Storage
More than 50% and
sometimes up to 80% of cholesterol which is absorbed from intestines is
secreted by liver and is a part of bile. Ingested cholesterol requires fat for
its absorption from the lumen of the intestine into the lymphatics. These are esterified
with fatty acids in the intestinal epithelium during their passage into the
lymphatics.
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 intake in diet is 300
mg daily for average person.
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 ingestion, has little effect on concentrations of
cholesterol in the blood. During the first seven hours after ingestion of
cholesterol, as absorbed fats 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.
Plants
make cholesterol in very small amounts. In larger quantities they
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, 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. A good portion
of cholesterol remains in the cells of reticulo endothelial system. It is
utilized in various body functions and mostly recycled.
Functions
of cholesterol
1. Essential constituent of all cells-It is a part of the element constant
of the cells. 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 non polar 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 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.
2. Controls cell permeability and transport-As it maintains integrity
of cell membrane it controls the permeability of the cells. Within the cell membrane, cholesterol also functions
in intracellular transport, cell signaling and nerve conduction.
3. Prevents haemolysis- Low blood cholesterol is associated with
haemolysis.
4. Defensive action- Cholesterol is intimately related to the
defensive mechanism of the body. During acute infections blood cholesterol
falls and tends to rise during recovery.
5. Fat transport- A large part of fat is transported through blood as
cholesterol esters.
6. Formation of cholic acid (bile salts) -Cholesterol is the mother
substance from which cholic acid is synthesized. Cholic acid is a constituent
of bile salts.
7. Antilipotropic action- Cholesterol feeding increases the
deposition of fat in the liver. This effect is due to the formation of cholesterol
esters and depression of phospholipid formation in the liver.
8. Controls cell division-Rapidly growing tissues are very rich in
cholesterol, such as, the granulation tissues of healing ulcer and rapidly
growing tumours, etc.
9. Antagonistic to phospholipids-Its physicochemical properties are
antagonistic to phospholipids; hence, they are always found together.
10. Parent substance-It is a parent substance of all the steroid
hormones of sex glands, adrenal cortex as well as Vitamin D.
Excretion
of cholesterol
Excretion takes place
in the following ways:
(1) Through bile-It is found as free
cholesterol but a good part of it is reabsorbed from the intestine.
(2) Through feces-A part of the bile
cholesterol undergoes bacterial putrefaction in the intestine and is excreted
as coprosterol. But a small amount of free cholesterol is also found in the
stool.
(3) Through urine-It appears in the urine
only in traces, but appears in larger amounts in different diseases namely in
hypercholesteremia.
(4) Through skin-Sebum, secretion of the
sebaceous glands of the skin contains large quantities of cholesterol and thus
drying of the skin is prevented by sebum due to its cholesterol constituent.
Blood
cholesterol in pregnancy- During pregnancy blood
cholesterol rises and rapidly comes back to normal after delivery. It may be
that this rise is due to hyperactivity of the adrenal cortex, produced during
pregnancy and the exact function is not known. It may be associated with the
rapid cell division and the tissue differentiation of the foetus. This high
cholesterol ensures the supply of the mother substance from which large amounts
of sex hormones are manufactured during pregnancy.
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