Published on February 3, 2014
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) HMG CoA Reductase Mevalonate Prenylation of signalling peptides (ras, rho, etc.) Isopentenyl adenine (transfer RNA) Farnesyl Pyrophosphate Dolichols Cholesterol Inhibition of other key products of mevalonate may relate to nonlipid effects & rare side effects of statins.
Regulation 1. Dietary Cholesterol: Increase in Dietary 2. Feed-back Control: Increase in Cholesterol 3. cholesterol Causes Decrease in Denovo synthesis. causes Inhibition of HMGCoA Reductase synthesis (regulation of gene expression) and Inactivation of Remaining enzymes Liver: a) By LCAT mechanism b) Bile acids/salts c) Incorporation into VLDL
Metabolic Fates of Cholesterol Steroid Hormones Vitamin D Cholesterol Incorporation into Biological Membranes Bile Acids
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 Glucocorticoids (cortisol) Starvation Potassium excretion Hepatic gluconeogenesis Muscle protein degradation Adipose lipolysis Adrenal androgens Dehydroepiandroterone (DHEA) Precurser to potent androgens in extraadrenal tissues
Calcification Inhibitors in CKD and Dialysis Patients
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