1. Cholesterol metabolism

2. Cholesterol Cholesterol is the precursor of all other steroids
Plays an important structural role in membranes
Cholesterol is synthesized from acetyl-CoA
Cholesterol synthesis in the liver is regulated
Excess cholesterol is excreted from the liver

3. Reverse cholesterol transport
Plasma low-density lipoprotein (LDL) is the vehicle of uptake of cholesterol and cholesteryl ester into many tissues
Reverse cholesterol transport
Free cholesterol is removed from tissues by plasma high-density lipoprotein (HDL) and transported to the liver
Eliminated from the body
either unchanged or after conversion to bile acids

4. CHOLESTEROL is derived about equally
FROM THE DIET
& FROM BIOSYNTHESIS
Endoplasmic reticulum and the cytosol.
The biosynthesis of cholesterol may be divided into five steps
Synthesis of mevalonate
Formation of Isoprenoid units

5. Six isoprenoid units condense to form squalene
Squalene cyclizes to give rise to lanosterol.
Cholesterol is formed from lanosterol

9. Regulation of cholesterol synthesis
at the HMG-CoA reductase step
In starving animals is accompanied by a decrease in the activity
Inhibited by dietary cholesterol
Hepatic synthesis
Regulating the rate of protein synthesis
Posttranslational modification
Increase HMG-CoA reductase activity
Insulin or thyroid hormone
Decrease
Glucagon or glucocorticoids

11. Regulation of cholesterol synthesis
In the liver
regulated partly by cholesterol in the diet
In tissues
Cholesterol balance is maintained between the factors causing gain of cholesterol and the factors causing loss of cholesterol

12. FACTORS INFLUENCE THE CHOLESTEROL BALANCE IN TISSUES
Cell cholesterol increase is due to
Uptake of cholesterol-containing lipoproteins
By receptors, eg,
The LDL receptor
The scavenger receptor
Uptake of free cholesterol from cholesterol-rich lipoproteins to the cell membrane
Cholesterol synthesis
Hydrolysis of cholesteryl esters by the enzyme cholesteryl ester hydrolase

13. FACTORS INFLUENCE THE CHOLESTEROL BALANCE IN TISSUES
Decrease is due to
efflux of cholesterol from the membrane to HDL
esterification of cholesterol
Utilization of cholesterol for synthesis of other steroids

14. The LDL Receptor High-affinity Low-affinity Scavenger pathway
The apo B-100, E receptor
Highly Regulated
Low-affinity
not regulated
Scavenger pathway

15. Influx of cholesterol Inhibits HMG-CoA synthase, HMG-CoA reductase
Stimulates ACAT activity
Down-regulates synthesis of the LDL receptor

17. Transport of cholesterol between the tissues in humans.

18. Reverse cholesterol transport
HDL (preβ-HDL, discoidal, or HDL3) takes up cholesterol from the tissues and LCAT esterifies it and deposits it in the core of HDL, which is converted to HDL2.
The cholesteryl ester in HDL2 is taken up by the liver, either directly or after transfer to VLDL, IDL, or LDL via the cholesteryl ester transfer protein.

19. CHOLESTEROL IS EXCRETED FROM THE BODY
AS CHOLESTEROL
BILE ACIDS (SALTS)
a major pathway for the elimination of cholesterol.

21. Atherosclerosis & Coronary Heart Disease
HDL (HDL2) concentrations and coronary heart disease
the most predictive relationship is the LDL:HDL cholesterol ratio.

22. Diet Can Play an Important Role in Reducing Serum Cholesterol
polyunsaturated and monounsaturated fatty acids
Up-regulation of LDL receptors
Saturated fatty acids cause the formation of smaller VLDL particles
Contain relatively more cholesterol
Utilized by extrahepatic tissues at a slower rate

23. Factors associated with elevation of plasma FFA Regular exercise
Lowers plasma LDL
Raises HDL

24. Reduction of Serum Cholesterol & Triacylglycerol
Diet
Hypolipidemic Drugs
Block the reabsorption of bile acids
cholestyramine resin
blocking the absorption of cholesterol
Sitosterol
Statins
Clofibrate and gemfibrozil
decreasing the secretion of triacylglycerol and cholesterol-containing VLDL by the liver
Stimulate hydrolysis of VLDL

25. Reduction of Serum Cholesterol & Triacylglycerol
Probucol
increase LDL catabolism via receptor independent Pathways
Antioxidant properties
Nicotinic acid
inhibiting adipose tissue lipolysis
reduces the flux of FFA
Inhibiting VLDL production by the liver.

26. Disorders of the Plasma Lipoproteins
Primary (Dyslipoproteinemias)
Are Inherited
Secondary abnormal lipoprotein patterns