3. INTRODUCTION
Cholesterol is a waxy, fat-like substance
that's found in all the cells in your body.
cholesterol to make hormones, vitamin D
etc.
Cholesterol is also found in foods from
animal sources, such as egg yolks, meat,
and cheese.
Cholesterol is a lipid with a unique
structure consisting of four fused
hydrocarbon rings forming the bulky
steroid structure. There is a hydrocarbon
tail linked to one end of the steroid and a
hydroxyl group linked to the other end.
4. CONT….
What are HDL, LDL, and VLDL?
HDL stands for high-density lipoprotein. It is called
the "good" cholesterol because it carries
cholesterol from other parts of your body back to
your liver. Your liver then removes the cholesterol
from your body.
LDL stands for low-density lipoprotein. It is called
the "bad" cholesterol because a high LDL level leads
to the buildup of plaque in your arteries.
VLDL stands for very low-density lipoprotein. It is
also a "bad" cholesterol because it too contributes
to the buildup of plaque in your arteries. But VLDL
and LDL are different; VLDL carries triglycerides and
LDL carries cholesterol.
5. BIOSYNTHESIS OF CHOLESTEROL
Slightly less than half of the cholesterol in the body derives from biosynthesis de
novo.
The cholesterol biosynthesis pathway involves enzymes that are in the
cytoplasm, microsomes (ER), and peroxisomes. Synthesis of cholesterol, like that
of most biological lipids, begins from the two-carbon acetate group of acetyl-
CoA.
The acetyl-CoA utilized for cholesterol biosynthesis.
The isoprenoid intermediates of cholesterol biosynthesis can be diverted to
other synthesis reactions.
The process of cholesterol synthesis can be considered to be composed of five
major steps where the reactions that culminate in the synthesis of isopentenyl
pyrophosphate, and its isomeric form dimethylallyl pyrophosphate, are
commonly referred to as the mevlonate pathway:
6. CONT….
1.HMG-CoA Synthesis
Acetyl-CoA units are converted to mevalonate by a series of reactions that begins
with the formation of HMG-CoA.
The cytoplasmic thiolase enzyme involved in cholesterol biosynthesis.
2. Mevalonate Synthesis
HMG-CoA is then converted to mevalonate by HMG-CoA reductase, HMGR (this
enzyme is bound in the endoplasmic reticulum, ER).
he reaction catalyzed by HMGR is the rate limiting step of cholesterol
biosynthesis,
3. Isopentenylpyrophosphate (IPP) Synthesis
mevalonate 5-diphosphate, an ATP-dependent decarboxylation yields
isopentenyl pyrophosphate (IPP) which is an activated isoprenoid molecule.
7. CONT….
4.Squalene Synthesis
The synthesis of squalene, from FPP, represents the first cholesterol-specific step
in the cholesterol synthesis pathway.
several intermediates in the pathway can be diverted to the production of other
biologically relevant molecules. The synthesis of squalene is catalyzed by the
NADPH-requiring enzyme.
5. Squalene to Cholesterol
Squalene then undergoes a two step cyclization to yield lanosterol. The first
reaction in this two-step cyclization is catalyzed by the enzyme, squalene
epoxidase (also called squalene monooxygenase).
Through a series of 19 additional reactions, lanosterol is converted to
cholesterol. These 19 reaction steps are catalyzed by nine different enzymes that
are localized either to the ER or to the peroxisomes.
9. DEGRADATION OF CHOLESTEROL
Cholesterol will be convert into bile acid steroid & vitamin d.
Bile acid
The bile acids are synthesized in the liver from cholesterol.
Bile acids are amphipathic in nature.
Participate in digestion & absorption of lipids.
On conjugation with glycine or taurine , conjugated bile acids formed, namely
Glycocholic acid & taurocholic acid.
Fecal excretion of bile salts is only route for removal of cholesterol from body.
11. CLINICAL SIGNIFICANCE
Hypercholesterolemia
High cholesterol, also known as
hypercholesterolemia, is a major risk factor for
heart disease and stroke.
High cholesterol is associated with an elevated risk
of cardiovascular disease.
High cholesterol has also been linked to diabetes
and high blood pressure.
Reduced blood flow can result in angina (chest
pain)or in a heart attack if a blood vessel gets
blocked completely
If a arteries vessel carrying blood to the brain is
blocked completely, you could have a stroke.
High blood pressure (also called hypertension) and
high cholesterol also are linked.
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Hypocholesterolemia
Abnormally low levels of cholesterol are termed
hypocholesterolemia.
but some studies suggest a link with depression,
cancer, and cerebral hemorrhage.
A genetic defect in cholesterol synthesis causes
Smith-Lemli-Opitz syndrome.
Hyperthyroidism, or any other endocrine
disturbance which causes upregulation of the LDL
receptor, may result in hypocholesterolemia.
Cholesterol testing
The American Heart Association recommends
testing cholesterol every 4–6 years for people aged
20 years or older.
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
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This measures total cholesterol, LDL ("bad") cholesterol, HDL ("good")
cholesterol, and triglycerides.
HDL ("good") cholesterol less than 1 mmol/L (40 mg/dL), or there are other risk
factors for heart disease and stroke. Other risk factors for heart disease include
diabetes mellitus, hypertension (or use of anti-hypertensive medication), low
HDL level, family history of coronary artery disease (CAD) and
hypercholesterolemia, and cigarette smoking.
15. INTRODUCTION
Hormones are chemical messengers that
transport of signal from one cell to another
Steroid act via intracellular receptors
Steroids are lipophilic, low-molecular
weight compounds derived from cholesterol
that play a number of important
physiological roles.
. If their biological function is essential,
terms like " a glucocorticoid " or " sex
steroids “
The parental precursor of steroids -
cholesterol
17. BIOSYTHESIS OF STEROID HORMONES
steroid hormones are synthesized from the
enzymaticaly modified cholesterol.
produced directly from cholesterol, the
precursor molecule for all C18, C19 and C21
steroids.
adrenal cortex.
Composed of 3 layers (zones).
outer zone (zona glomerulosa) produces
aldosterone (mineralocorticoid).
middle zone (zona fasciculata) produces cortisol
(glucocorticoid).
inner zone (zona reticularis) produces androgens.
18.
19. SIDE EFFECT OF STEROID
liver disease, such as liver tumors and cysts.
kidney disease.
heart disease, such as heart attack and stroke.
high blood pressure.
azoospermia (absence of sperm in semen).
menstrual irregularities in women.
altered mood, irritalibity, increased aggression, depression or suicidal
tendencies.
THE END
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