ENZYMES, RESEPTORS, ANTIOXIDANTS AND LIPID

ENZYMES, RESEPTORS, ANTIOXIDANTS AND LIPIDS

Enzymes

Lipoprotein lipase (LPL), found in muscle and adipose tissue capillaries, hydrolyses lipoprotein triglycerides. Hepatic lipase also hydrolyses lipoprotein triglyceride and is involved in the conversion of IDL to LDL. Cholesterol synthesis is controlled by 3-hydroxy-3methylglutaryl coenzyme A reductase (HMG-CoA reductase). Non-hepatic cells receive most of their cholesterol from LDL not from endogenous synthesis. A fall in cell cholesterol up regulates HMG-CoA reductase. A great deal of the lipoprotein-cholesterol that is secreted subsequently returns to the liver, either on LDL or from reverse transport on HDL.

Lecithin cholesterol acyltransferase (LCAT), which accompanies HDL, esterifies free cholesterol, the ester moving to the HDL core. HDL3 becomes the larger HDL2; this process may be reversed by hepatic lipase. LCAT aids the removal of phospholipids and free cholesterol from VLDL during catabolism, and also their passage to HDL.

Lipids exchange between lipoproteins and there is active enzyme-mediated transfer. Cholesterol ester transfer proteins (CETP) pass HDL cholesterol ester to VLDL with reverse movement of triglycerides: this limits the accumulation of cholesterol ester in HDL, However, excess cholesterol ester in VLDL may not be physiologically appropriate.

Receptors

Lipoproteins are recognizes apoB100, and IDL apoE, taking up cholesterol into the cell. Higher cholesterol levels in the cell lead to :
1. Increased acyl cholesterol acyltransferase (ACAT) activity with cholesterol re-esterification.
2. Inhibition of HMG-CoA reductase and cholesterol synthesis.
3. Decreased new LDL-receptor synthesis and membrane insertion.
LRP binds multiple apoE copies on chylomicron remnants, facilitating their hepatic removal.

Atherosclerotic plaques are an inflammatory response to vessel wall injury; they contain macrophages and T lymphocytes, and have cytokine and growth factor expression. Endothelium modifies LDL, with phospholipid peroxidation and apoB degradation.

Activated macrophage with acetyl-LDL or oxidized-LDL receptors avidly remove modified LDL. Macrophage uptake may be a helpful scavenging mechanism, but in excess macrophage become lipid-laden foam cells of the fatty streak, which have a pivotal role in atherogenesis.

Antioxidants

Antioxidants may protect LDL from oxidative damage, and may be anti-atherogenic. The antioxidants vitamin E and β-carotene are carried on LDL. Changes in diabetic metabolism that predispose to lipoprotein oxidation may accelerate atherogenesis.


See images as description on the links below :
1.Lipid (cholesterol); transport, penetration, and balance
2.Forming of The Mixed micelle
3.Helical wheel projection of a portion of ApoA-I