Apoprotein E

In adult brain most cholesterol synthesis occurs in astrocytes. Apoprotein E (apoE) is the major apolipopro-tein of the CNS and it is secreted by astrocytes. In astrocyte cultures apoE appears in the media as cholesterol-rich particles of a size similar to peripheral HDL (5-12 nm) (Fig. 2-7). The ATP-dependent transporter ABCA1, expressed by both astrocytes and neurons, promotes the formation of the apoE-stabilized high-density lipoprotein (HDL)-sized particles from astrocytic cholesterol. 

Mahley R. W. (1988). Apoprotein E cholesterol transport protein with expanding role in cell biology. Science 240 622-630. 

R.C. Kowal, J. Herz, J.L. Goldstein, V. Esser and M.S. Brown, Low density lipoprotein receptor related protein mediates uptake of cholesteryl esters derived from apoprotein E-enriched lipoproteins, Proc. Natl. Acad. Sci. USA 86 (1989) 5810-5814. 

Wll. Weisgraber, K. H., and Mahley, R. W., Apoprotein (E-A-II) complex of human plasma lipoproteins. I. Characterization of this mixed disulfide and its identification in a high density lipoprotein subfraction. J. Biol. Chem. 253, 6281-6288 (1978). 

Phylloquinone is absorbed in the proximal small intestine, by an energy-dependent mechanism, and is incorporated into chylomicrons. Estrogens increase phylloquinone absorption in both male and female animals, and male animals are more susceptible to dietary vitamin K deprivation than females (loUy et al., 1977). Even after an overnight fast, about half the plasma vitamin K is present in chylomicron remnants, and only a quarter in low-density lipoprotein. The plasma concentration of phylloquinone is associated with genetic variants of apoprotein E, which determines the binding of chylomicron remnants to the liver lipoprotein receptor (Kohlmeier et al., 1996). 

Kallio, M., Salmenpera, L., Siimes, M., Perheentupa, J., Gylling, H., and Miettinen, T. A. (1997). Apoprotein E phenotype determines serum cholesterol in infants during both high-cholesterol breast feeding and low-cholesterol formula feeding. /. Lipid Res. 38, 759-764. 

The portion of a chylomicron that remains in the blood after LPL action is known as a chylomicron remnant. This remnant binds to receptors on hepatocytes (the major cells of the liver), which recognize apoprotein E, and is taken up by the process of endocytosis. Lysosomes fuse with the endocytic vesicles, and the... 

Type III hyperhpidemia is caused by a deficiency of apoprotein E. Analysis of the semm of patients with this disorder would exhibit which of the following ... 

The presence of apoprotein E in lipoproteins enables them to be taken up by hepatic cells. Provide a brief explanation for each of the following observations made of a person with a deficiency in apoprotein E synthesis. 

Function Transport dietary TAG and cholesterol from the intestines to the periphery Forward transport of endogenous TAG and cholesterol from liver to periphery Precursor of LDLs Cholesterol transport 1 Reverse transport of cholesterol from periphery to the liver 2 Stores apoprotein C2 and apoprotein E which it supplies to chylomicrons and VLDLs 3 Scavenges and recycles apolipoproteins released from chylomicrons and VLDL following lipoprotein lipase activity in the capillaries... 

Cole, T.G., Putsch, W., Kuisk, I., Gonen, B. and Schonfeld, G. (1983) Increases in dietary cholesterol and fat raise levels of apoprotein E-containing lipoproteins in the plasma of man. J. Clin. Endocrinol. Metab. 56, 1108-1115. 

Tan, M.H., Dickinson, M.A., Albers, J.J., Havel, R.J., Cheung, M.C. and Vigne, J. (1980) The effect of a high cholesterol and saturated fat diet on serum high-density lipoprotein-cholesterol, apoprotein A-I, and apoprotein E levels in normolipidemic humans. Am. J. Clin. Nutr. 33, 2559-2565. 

Give brief descriptions of the following (a) peptide (b) naturally occurring amino acids (c) metallo-protein (d) apoprotein (e) haem unit. 

Miura Y, Chiba T, Tomita I, Koizumi H, Miura S, Umegaki K, Hara Y, Ikeda M, Tomita T. Tea catecbins prevent the development of atherosclerosis in apoprotein E-deficient mice. J Nutr 2001 131 27-32. 

Apoprotein E, which binds to hepatic receptors for uptake of lipid-depleted chylomicron remnants. Chylomicron remnants are taken into the liver by receptor-mediated endocytosis, followed by hydrolysis of the proteins and the residual lipids. 

Poor affinity of some genetic variants of apoprotein E for the LDL receptor. This is the basis of some genetic susceptibility to atherosclerosis. 

Chemical modification of apoprotein E in the circulation, so reducing its affinity for the hepatic receptors. Commonly, this is secondary to oxidative damage to unsaturated fatty acids in LDL — hence the role of antioxidants in reducing the risk of atherosclerosis (section 7.4.3). High levels of homocysteine (section 11.11.3.3) can also lead to modification of apoprotein E. 

HDL, high density lipoprotein LDL, low density lipoprotein VLDL, very low density lipoprotein TAG, triacylglycerol FA, fatty acid IDL, intermediate density lipoprotein TCA, tricarboxylic acid CM, chylomicron DFIAP, dihydroxyacetone phosphate TAG, triacylglycerol FA, fatty acid ApoB, apoprotein B ApoC, apoprotein C LP lipase, lipoprotein lipase ApoE, apoprotein E... 

Among the apolipoproteins, polymorphism of apoprotein E apparently dictates a subject s chances for successful treatment of lipidemia. The apoE alleles are designated as E2, E3, and E4. The most common pattern (55%) is homozygosity for E3, which gives rise to the E3/E3 phenotype. The next most common phenotype is E3/E4 (26%). The least frequently observed phenotype is E2/E (1%), which is often associated with type III hyperlipoproteinemia. There is some evidence suggesting that subjects bearing the E4 allele have higher levels of LDL than those with the E3/E3 pattern they may also be more... 

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