Transport of cholesterol.
.ur current model for cholesterol transport is summarized in Figure 10. In this figure we have put together the various steps in cholesterol transport that were described previously in this review. Under normal conditions, cholesterol metabolism and transport are well regulated. If the transport system is overloaded for a long time, however, hypercholesterolemia caused mainly by increased plasma LDL may develop in several species, including humans. Under such circumstances reverse transport of cholesterol may also fail, giving rise to deposits of cholesterol. Tissue macrophages may be responsible for this lipid accumulation, because receptor-mediated (adsorptive) endocytosis of lipoprotein-associated cholesterol in these cells is not under negative-feedback control. The deposits are mainly found in tissues poorly supplied with blood and lymph: the skin, tendons, the cornea, and arteries. Overload of cholesterol transport may be the result of too much fat and cholesterol in the diet, giving rise to cholesterol-rich lipoproteins from the gut and to increased production of liver (formula; see text) VLDL, which in humans ends up as LDL. In many individuals, however, no hypercholesterolemia is seen, even after eating large amounts of a "western" diet for decades; others may develop increased LDL on a relatively "prudent" diet. Obviously many of the factors and mechanisms in cholesterol transport are influenced by genetic factors. Although studies of several inborn errors of lipid metabolism have given information about some mechanisms, the quantitatively more important differences in genetic patterns, which determine whether or not a western diet will result in hyperlipidemia, are not well known. Perhaps studies of different forms of apoB and apoE and of HDL subgroups and hyper-alpha-lipoproteinemia will explain why certain individuals develop hypercholesterolemia and premature atherosclerosis. All the recent information related to cholesterol metabolism and transport gives rise to new questions. There are many problems of interest for future research: What are the metabolic differences between the apoB produced in the liver and that produced in the gut? To what extent is the protein moiety of LDL modified in the plasma of blood and lymph and in interstitial tissue? Are such modifications important to whether LDL uptake goes through the classic LDL pathway or through the macrophage (i.e., scavenger?) pathway? Are some changes in apoB important for liver recognition of LDL?(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D001692:Biological Transport; D001808:Blood Vessels / Q000378:metabolism; D002784:Cholesterol / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D002788:Cholesterol Esters / Q000097:blood / Q000502:physiology; D006801:Humans; D007421:Intestine, Small / Q000378:metabolism; D008074:Lipoproteins / Q000096:biosynthesis / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008563:Membrane Lipids / Q000502:physiology; D008954:Models, Biological; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000378:metabolism; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
D002788:Cholesterol Esters; D008074:Lipoproteins; D008563:Membrane Lipids; D014280:Triglycerides; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D007862:Phosphatidylcholine-Sterol O-Acyltransferase; D002787:Sterol Esterase