All about Cholesterol ( for undergrads)
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Transcript of All about Cholesterol ( for undergrads)
Cholesterol and Compounds
AD
Cholesterol Def:
It is a steroid alcohol of animal tissue having 27 Carbon units, which performs essential functions in body.
Normal Blood Cholesterol: 150-250 mg/dl
Liver has a central role in regulating blood cholesterol level.
CHOLESTEROL SYNTHESIS, TRANSPORT, AND EXCRETION
A little more than half the cholesterol of the body arises by synthesis (about 700 mg/d), and the remainder is provided by the average diet. The liver accounts for 10% of total synthesis in humans, the intestine for about another 10%.
Microsomal (endoplasmic reticulum) and cytosol fraction of the cell is responsible for cholesterol synthesis.
HMG CoA Reductase(More Than Cholesterol Synthesis)
3Acetyl CoA (2C)
HMG CoA(6C)
Mevalonate
Farnesyl Pyrophosphate
Cholesterol
HMG CoA ReductaseIsopentenyl
adenine(transfer RNA)
Prenylation ofsignalling peptides(ras, rho, etc.)
Dolichols
Inhibition of other key products of mevalonate may relate tononlipid effects & rare side effects of statins.
Regulation
1. Dietary Cholesterol: Increase in Dietary cholesterol Causes Decrease in Denovo synthesis.
2. Feed-back Control: Increase in Cholesterol causes Inhibition of HMGCoA Reductase synthesis (regulation of gene expression) and Inactivation of Remaining enzymes
3. Liver: a) By LCAT mechanism
b) Bile acids/saltsc) Incorporation into VLDL
Metabolic Fates of Cholesterol
Cholesterol
Steroid Hormones
Vitamin D Bile Acids
Incorporation into Biological Membranes
Types of Bile Acids/Salts
Primary bile acids Good emulsifying
agents All OH groups on same
side pKa = 6 (partially
ionized)
Conjugated bile salts Amide bonds with
glycine or taurine Very good emulsifier
pKa lower than bile acids
Recycling of Bile Acids Enterohepatic
circulation 98% recycling of
bile acids
Steroid Hormone Metabolism:Adrenal Steroid Hormones
Aldosterone C21 derivative of cholesterol Promotes renal Sodium retention
Potassium excretion Glucocorticoids (cortisol)
Starvation Hepatic gluconeogenesis Muscle protein degradation Adipose lipolysis
Adrenal androgens Dehydroepiandroterone (DHEA)
Precurser to potent androgens in extra-adrenal tissues