Cholesterol metabolism

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Cholesterol biosynthesis, regulation and important compounds

Cholesterol biosynthesis, regulation and important compounds

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  • All steroids have a similar cyclic nucleus resembling phenanthrene (rings A, B, and C) to which a cyclopentane ring
    (D) is attached. The carbon positions on the steroid nucleus are numbered as shown in Figure 15–14. It is
    important to realize that in structural formulas of steroids, a simple hexagonal ring denotes a completely saturated
    six-carbon ring with all valences satisfied by hydrogen bonds unless shown otherwise; ie, it is not a benzene ring.
    All double bonds are shown as such. Methyl side chains are shown as single bonds unattached at the farther
    (methyl) end. These occur typically at positions 10 and 13 (constituting C atoms 19 and 18). A side chain at
    position 17 is usual (as in cholesterol). If the compound has one or more hydroxyl groups and no carbonyl or
    carboxyl groups, it is a sterol,and the name terminates in -ol.

Transcript

  • 1. Dr. Vijay Marakala, MBBS, MD. Senior Lecturer BIOCHEMISTRY IMS, MSU.
  • 2. CHOLESTEROL No vegetable oil contains any cholesterol. Cholesterol is the major sterol in animal tissues. Only a little portion of the body cholesterol is derived from diet. The bulk of it is synthesized in the body.
  • 3. CHOLESTEROL BIOSYNTHESIS
  • 4. •All the carbon atoms of cholesterol are derived from acetyl CoA •Liver and Intestine are major sites of cholesterol
  • 5. STEPS OF DE NOVO CHOLESTEROL SYNTHESIS • Step 1—Biosynthesis of Mevalonate • Step 2—Formation of Isoprenoid Units • Step 3—Six Isoprenoid Units Form Squalene • Step 4—Formation of Lanosterol • Step 5—Formation of Cholesterol
  • 6. Acetoacetyl-CoA HMG-CoA Several steps
  • 7. 3 Acetyl-CoA HMG-CoA Mevalonate Isopentenyl pyrophosphate X6 Squalene Lanosterol Cholesterol C6 C5 C30 C30 C27
  • 8. Regulation of de novo synthesis of cholesterol HMG-CoA reductase Feedback regulation Hormonal regulation Nutritional regulation
  • 9. HMG-CoA reductase (active) HMG-CoA reductase (Inactive) Acetyl-CoA HMG-CoA Mevalonate CHOLESTEROL Insulin Glucagon Increased caloric intake, Thyroid hormone Bile acids, glucocorticoids, Dietary cholesterol P Dephosphorylation Phosphorylation + + + -
  • 10. Competitive inhibitor drugs of HMG- CoA REDUCTASE PARVASTATIN LOVASTATIN MEVASTATIN SIMVASTATIN FLUVASTATIN
  • 11. IMPORTANT COMPUNDS SYNTHESIZED FROM CHOLESTEROL
  • 12. CHOLESTEROL-BIOLOGICAL IMPORTANT COMPONDS CHOLESTEROL BILE ACIDS STEROID HORMONES VITAMIN D
  • 13. FORMATION OF BILE ACIDS • Bile acids are synthesized in the liver from cholesterol. • They contain 24 carbon atoms Cholic acid Chenodeoxycholic acid
  • 14. Cholesterol 7-α- hydroxyl cholesterol Bile acids Vitamin C O2 H2O 7-α- hydroxylase
  • 15. FORMATION OF STEROID HORMONES Cholesterol Progesterone Androgens Estrogens Glucocorticoids Mineralocorticoids
  • 16. Cholesterol 7-dehydrocholesterol CHOLECALCIFEROL [Vitamin D3] UV light Dehydrogenase FORMATION OF VITAMIN D
  • 17. BLOOD CHOLESTEROL Free cholesterol about 30% Ester form(cholesterol ester) is about 70% Blood levels are influenced by both genetic and environmental factors
  • 18. EXCRETION OF CHOLESTREROL • Cholesterol is excreted in faeces • Cannot be destroyed by oxidation to CO2 and H2O, because of absence of enzyme capable of catabolising the steroid nucleus • About 1gm of cholesterol is eliminated from the body per day
  • 19. DISORDER OF CHOLESTEROL METABOLISM FAMILIAL HYPERCHOLESTEROLAEMIA Deficiency or malfunction of LDL receptors Plasma LDL & cholesterol level are elevated ATHEROSCLEROSIS Deposition of cholesterol and other lipids in the arterial wall Leads to formation of plaque→endothelial damage→IHD