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The following points highlight the fourteen main processes to transport lipids in human.
1. The major plasma lipids do not circulate in the free form, rather free fatty acids (FFA) are bound to albumin, whereas cholesterol, triglycerides and phospholipids are transported in the form of lipoprotein complexes. The density of these lipoproteins is inversely proportional to their lipid content.
2. The proteins of the lipoproteins are called Apo proteins and the major Apo proteins are called apo E, apo C, apo B-48, and apo B- 100. Apo B-48 having a low molecular weight is the characteristic of the exogenous system, whereas apo B-100 having a high molecular weight is the characteristic of the endogenous system.
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3. Chylomicrons, formed in the intestinal mucosa during the absorption of the products of fat digestion, are very large lipoprotein complexes that enter the circulation through the lymphatic ducts. The plasma shows the milky appearance (lipemia) after meals due to the presence of many of these particles in the blood.
These chylomicrons are cleared from the circulation by the action of lipoprotein lipase which is present on the surface of the endothelium of the capillaries.
The triglycerides of these chylomicrons are broken down to glycerol and free fatty acid which then enter adipose cells and are re-esterified by the catalytic action of the lipoprotein lipase. Lipoprotein lipase, with the help of heparin as a cofactor, also removes triglycerides from circulating very low density lipoproteins’ (VLDL). Apoliprotein C-11 activates lipoprotein lipase.
4. Chylomicrons remain in the circulation as cholesterol-rich lipoproteins called chylomicron remnants which are carried to the liver where they bind to chylomicron remnant and LDL receptors and are degraded in lysosomes. The chylomicrons and their remnants form a transport system for ingested exogenous lipids.
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5. The endogenous system made up of VLDL, intermediate density lipoproteins (IDL), low density lipoproteins (LDL) and high density lipoproteins (HDL) transports triglycerides and cholesterol throughout the body.
6. VLDL are formed in the liver and transport triglycerides to extra-hepatic tissues.
7. IDL is formed when triglyceride is largely removed by the action of lipoprotein lipase. The IDL give up phospholipids and pick up cholesteryl esters formed from cholesterol in the HDL by the action of the plasma enzyme lecithin cholesterol acyltransferase (LCAT).
The liver takes up some IDL and the remaining IDL then lose more triglyceride and protein in the sinusoids of the liver and become LDL. During this conversion, they lose apo E but apo B-100 remains intact.
8. Cholesterol is provided to the tissues by LDL. This cholesterol is an essential constituent of cell membranes and is used by the gland cells to form steroid hormones.
9. LDL are taken up by receptor-mediated endocytosis in coated pits in the liver and most extra hepatic tissues. The receptors recognize the apo B-100 component of the LDL and bind apo E but not apo B-48. The human LDL receptor is a complex molecule made up of a cysteine-rich region of 292 amino acid residue that binds LDL.
10. Cholesterol in the cells inhibits intracellular synthesis of cholesterol by inhibiting HMG-CoA reductase, stimulates esterification of any excess cholesterol that is released and inhibits the synthesis of new LDL receptors.
11. Macrophage specially take up LDL which are modified by oxidation and antioxidants like vitamin E and, as a result, the progress of atherosclerosis becomes slow. The LDL receptor on macrophages and related cells is called Scavenger receptor.
12. Cholesterol leaves as well as enters cells. The cholesterol leaving the cells is absorbed in HDL, lipoproteins that are synthesized in the liver and the intestine. Some of the HDL contain apo E and bind to LDL receptors on other cells transporting cholesterol from one cell to another.
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13. Through LCAT, HDL provides the cholesteryl esters which are transferred to IDL and then back again to LDL.
14. Apo E is synthesized by astrocytes in the brain and by cells in the spleen, lung, ovary, kidney, and liver. Its concentration is highly increased in injured nerves where it plays an important role in nerve regeneration by adjusting the cholesterol concentration during the repair process.
