Biochemistry of Cholesterol Metabolism: Lecture

Biochemistry of Cholesterol

1. Cholesterol metabolism and regulation Roll. 26-37

2. Cholesterol Biosynthesis LOCATION All tissues containing nucleated cells Liver (Major site) Intestine Adrenal cortex Reproductive tissues like gonads and placenta Smooth endoplasmic reticulum and cytosol

3. Requirement Acetyl-CoA NAD P H ATP

4. Steps of cholesterol biosynthesis Synthesis of mevalonate from acetyl-CoA Formation of isoprenoid units from mevalonate by loss of CO 2 Condensation of six isoprenoid unit to form squalene Cyclization of squalene give rise to a) parent steroid , lanosterol b) and then cholesterol

5. Step 1

6. Fate of HMG C o A

7. STEP 2

8. Isoprenoid Units I soprenoid, any of a class of organic compounds composed of  two or more units of hydrocarbons , with each unit consisting of five carbon atoms arranged in a specific pattern. Isoprene unit : C 5 H 8

9. STEP 3 GFS 2 3 6

10. Step 4a

11. SPF Supernatant protein factor P rotein that stimulates squalene epoxidation , mediates the transfer of squalene between two separable microsomal populations

12. Microsomes Microsomes are a collection of vesicles that are formed when cells are broken down in a laboratory N ot present in healthy, living cells . M ade up of three structural features: rough vesicles, smooth vesicles, and ribosomes. They are isolated by differential centrifugation To Study Enzyme inhibition Rates and efficiency of clearance Metabolite identification Drug-drug interactions

13. Epoxide Formation

14. STEP 4 b ER Membrane 14, 4, 8, 24

15. SUMMARY

16. Regulation

17. Inhibition by statins

18. SREBP Sterol regulatory element-binding proteins (SREBPs) SREBP cleavage-activating protein (SCAP) Insig (insulin-induced gene Protein

19. thank you

20. Credits Slides of respected Dr. Ankit sir Swayam Pattnaik - image Wikipedia