Biochemistry

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Cholesterol

Cholesterol is a steroidal lipid that is present in


all animal tissues.
A steroid is an organic compound with four
fused rings (designated A, B, C, and D) arranged
in a specific molecular configuration.

Role of liver in cholesterol


homeostasis
Liver plays important role in the maintenance of
a specific balance of cholesterol within the
body.
Cholesterol enters into the body via HDL ,diet
and By denovo synthesis of cholesterol.
Similarly cholesterol leaves the body by its
excretion through bile acids and bile salts
Moreover, it is also secreted in the form of free
cholesterol to maintain its normal amount
eithin the body but somestiimes its
concentration will be increased than normal
And its reason is still unknown.

Cells involved in production of


cholesterol:-
Virtually almost all cells are involved in
production of Cholesterol.
But Liver,adrenal cortex,Ovaries,small intestine
and Testes play a primary role.
Liver act as a main site for de novo cholesterol
synthesis contributing to approximately 80% of
total cholesterol synthesis in mammals

Site of occurrence
Cholesterol synthesise occure in WELL Fed state
.
In cytoplasm and Smooth endoplasmic
reticulum.
Energy expensive process.

Steps of cholesterol synthesis:-


1.Condensation of 3 Acetyl CoA to Mevalonate
2.Mevalonate to activated Isoprenoid units
3.Polymerization of 6 isoprenoid units to
Squalene
4.Cyclization of Squalene to form Lanosterol
5.Formation of Cholesterol from Lanosterol

1.Condensation of 3 Acetyl CoA


to
HMG Co-A
Two molecules of Acetyl coenzymeA combine in
the presence of thiolase enzyme to form
acetoacetyl CoA.Then ,this molecule will be
converted to HMG co-A IN the presence of
HMG co A synthase.This reaction also needs
Acetylco A molecule.

Mevalonate Synthesis
HMG Co-A then will be transformed to
Mevalonate in the presence of HMGCo-A
reductase which is a Rate limiting or rate
determining step .
This enzyme is regulated by different factors
such as hormonal regulation and gene
expressions etc
Mevalonate molecule then undergoes
phosphorylation by three molecules of ATP in
several steps that results in formation of 3
phospho 5 pyrophospho mevalonate.
After its Decarboxylation it will form the
isoprenoid Unit .
HMG CoA reductase
Statins inhibit this enzyme

Statins: Cholesterol. lowering medications that


reduce cardiovascular disease risk.
Atorvastatin (Lipitor)
Simvastatin Rosuvastatin (Crestor)
Pravastatin (Pravachol)Lovastatin

Requirements and energy Cost


• Acetyl CoA provides all carbon atoms.
• Reducing equivalents are supplied by NADPH.
• ATP provides energy.
• For production of one molecule of
cholesterol...
• 18 moles of acetyl CoA
.36 moles of ATP
• 16 moles of NADPH are required.

Fates of Cholesterol
About 65% of cholesterolin body present in the
form cholesterol eaterase.
7 dehydro Cholesterol converts to
VitaminD3 in presence of UV rays .
Cholic Acid forms Bile Salts
Cholesterol Precursor in
steriod hormones production.

Hypercholesterolemia
Gentic Disorder
High level of LDL ( bad cholesterol)
Result in Xanthomas and Coronary Artery
Diseases

Treatment
Low Fat diet
Statins
Nicotinic Acid

ATHEROSCLEROSIS
It is the formation and deposition of lipid-rich
plaques in the intima of arteries.
These plaques then become fibrous and may
occlude an artery and cause a myocardial in-
farct or a cerebral infarct.

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