Biochem 501 Lecture 28: Cholesterol Regulation and Lipoproteins

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Biochem 501 Lecture 28: Cholesterol Regulation and Lipoproteins
2013-11-12 14:16:04
Biochem 501

Biochem 501
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  1. Regulation of Cholesterol Synthesis
  2. High Cholesterol is correlated with what
    Heart Disease
  3. Lipoproteins
    Blood borne proteins that transport Cholesterol/lipids
  4. Transport of exogenously derived cholesterol/triglys
    Carried to tissues by lipoproteins called chylomycrons. Try to give off to cells that need it before getting to liver
  5. Transport of endogenously derived choles/triglys
    Carried from liver by very low density lipoproteins (VLDL), after delivery they are intermediate density lipoproteins (IDL), then low density lipoproteins (LDL) which are taken to liver/peripheral tissue cells by receptor mediated endocytosis
  6. Hypercholesterolemia
    • Caused by absence of LDL receptors in liver
    • Causes: Elevation of plasma LDL cholesterol, deposition of cholesterol on blood vessel walls/heart attacks)
  7. What carries excess cholesterol from tissues?
    • High density lipoproteins, to the liver.
    • This cholesterol can be excreted via bile acids
  8. What carries "good" cholesterol and what carries "bad" cholesterol
    • HDL carries good and LDL carries bad.
    • HDL carries good because it is leaving body
    • LDL carries bad because it is depositing it places it shouldn't be.
  9. Blood plasma levels show a massive increase in what after a fatty meal?
    • Lipoproteins, make plasma milky
    • Fat will separate to top after centrifuge or letting it sit, is lighter than plasma
  10. Relative size of Lipoproteins
    • Chylomicrons>VLDL>IDL>LDL>HDL
    • Relative density is opposite
  11. Lipoproteins and what they carry
    • Chylomicrons: Dietary triacylglycerols
    • VLDL,IDL, LDL: Endogenous triacylglycerols, cholesterol esters, cholesterol
    • HDL: Cholesterol Esters and Cholesterol
  12. Apolipoproteins
    • The protein component of lipoproteins, lipoproteins are the whole package
    • Denser lipoproteins have a higher percentage of apoprotein in their make up
  13. Visualization of Lipoproteins size and make-up
  14. Formation of Cholesterol Esters

  15. Lipoprotein Structure
  16. LDL Receptor
  17. Process of Receptor Mediated Endocytosis
  18. Triacylglycerol to fatty acid cycle Part One
  19. Triacylglycerol to fatty acid cycle Part Two
  20. Triacylglycerol to fatty acid cycle Part Three
  21. Model for Plasma Triglyceride/Cholesterol Transport
  22. LDL Receptor Function: Normal
  23. LDL Receptor Function: Hypercholesterolemia
  24. LDL Receptor Function: High-Cholesterol Diet
  25. Atherosclerosis
    • Plaque build-up in blood vessel

    1.Infection damages inner lining of artery (red)

    • 2.As part of the healing process cholesterol is deposited on the damaged area
    • (yellow)

    3.A thin layer of congealed blood forms over the cholesterol (red)

    4.This layer prevents the body from removing the cholesterol plaque
  26. Consequences of Atherosclerosis
  27. Treatment of Atherosclerosis
    • Reduce Cholesterol Levels
    • Feed Lovastatin/Compactin to inhibit HMG-CoA reductase
    • OR
    • Feed Cholestyramine to reduce hepatic cholesterol pool
    • Cholesterol then binds to bile salts and is removed
    • This lowered hepatic cholesterol level upregulates LDL receptor levels and helps reduce "bad" cholesterol
  28. Statins do what, how?
    • Reduce LDL levels by inhibiting HMG-CoA reductase
    • This increases LDL receptors which decrease LDL levels