Hepatic clearance of plasma low density lipoproteins. 1992

D K Spady
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8887.

An elevated plasma LDL concentration is a major risk factor for the development of atherosclerosis and coronary heart disease. The concentration of LDL in plasma is determined, to a large extent, by events in the liver, since this organ is the source of LDL (via VLDL) and is the major site of LDL catabolism. LDL uptake by the liver is mediated largely by receptor-dependent mechanisms and fully 80 to 90% of whole body receptor-dependent LDL catabolism occurs in the liver. The rate of receptor-dependent LDL uptake by the liver is influenced by dietary and genetic factors. Cholesterol and fatty acids are the major dietary factors that alter receptor-dependent LDL uptake by the liver and appear to do so by regulating LDL receptor gene transcription. Regulation of LDL receptor gene transcription by sterols is mediated by sterol regulatory elements within the LDL receptor promoter, but how the nucleus actually senses cellular cholesterol levels and how dietary fatty acids might influence this process remain to be elucidated. Genetic factors may affect the basal rate of receptor-dependent LDL transport or the sensitivity of the LDL receptor pathway to regulation by dietary lipids. An understanding of how dietary lipids regulate hepatic LDL transport and plasma LDL levels, and identification of the major genetic factors that determine responsiveness to dietary lipids is crucial to the development of safe and effective dietary guidelines and to the selection of individuals most likely to benefit from diet modification.

UI MeSH Term Description Entries
D008077 Lipoproteins, LDL A class of lipoproteins of small size (18-25 nm) and light (1.019-1.063 g/ml) particles with a core composed mainly of CHOLESTEROL ESTERS and smaller amounts of TRIGLYCERIDES. The surface monolayer consists mostly of PHOSPHOLIPIDS, a single copy of APOLIPOPROTEIN B-100, and free cholesterol molecules. The main LDL function is to transport cholesterol and cholesterol esters to extrahepatic tissues. Low-Density Lipoprotein,Low-Density Lipoproteins,beta-Lipoprotein,beta-Lipoproteins,LDL(1),LDL(2),LDL-1,LDL-2,LDL1,LDL2,Low-Density Lipoprotein 1,Low-Density Lipoprotein 2,LDL Lipoproteins,Lipoprotein, Low-Density,Lipoproteins, Low-Density,Low Density Lipoprotein,Low Density Lipoprotein 1,Low Density Lipoprotein 2,Low Density Lipoproteins,beta Lipoprotein,beta Lipoproteins
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D011973 Receptors, LDL Receptors on the plasma membrane of nonhepatic cells that specifically bind LDL. The receptors are localized in specialized regions called coated pits. Hypercholesteremia is caused by an allelic genetic defect of three types: 1, receptors do not bind to LDL; 2, there is reduced binding of LDL; and 3, there is normal binding but no internalization of LDL. In consequence, entry of cholesterol esters into the cell is impaired and the intracellular feedback by cholesterol on 3-hydroxy-3-methylglutaryl CoA reductase is lacking. LDL Receptors,Lipoprotein LDL Receptors,Receptors, Low Density Lipoprotein,LDL Receptor,LDL Receptors, Lipoprotein,Low Density Lipoprotein Receptor,Low Density Lipoprotein Receptors,Receptors, Lipoprotein, LDL,Receptor, LDL,Receptors, Lipoprotein LDL
D002791 Cholesterol, Dietary Cholesterol present in food, especially in animal products. Dietary Cholesterol
D004041 Dietary Fats Fats present in food, especially in animal products such as meat, meat products, butter, ghee. They are present in lower amounts in nuts, seeds, and avocados. Fats, Dietary,Dietary Fat,Fat, Dietary
D005227 Fatty Acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed) Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D001692 Biological Transport The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments. Transport, Biological,Biologic Transport,Transport, Biologic

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