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