Abstract
Apolipoprotein A-I (apo A-I) is synthesized by hepatic and intestinal cells as preproapo A-I encompassing 267 amino acids of known sequence. Intracellular cleavage of 18 aminoterminal amino acids results in proapolipoprotein A-I that is the secreted isoform of apo A-I abundant in chylomicrons, intestinal and hepatic HDL precursors. A yet unidentified metalloenzyme removes the aminoterminal hexapeptid. The resulting mature apo A-I is the major protein component of HDL, the cofactor of the cholesterol esterifying enzyme lecithin:cholesterolacyltransferase (LCAT), and the putative ligand of a specific HDL receptor which helps to promote cholesterol efflux from many cells. Because of its in vitro functions apo A-I is supposed to be a key protein in reverse cholesterol transport, by which excess cholesterol is transported from peripheral cells to the liver for final deposition into the biliary tract (reviewed in Tall et al. 1990, Johnson et al. 1991). This model is supported by the epidemiological finding of an inverse correlation between HDL-cholesterol serum concentration and the risk for myocardial infarction (Gordon and Rifkind 1989), by the finding of an increased prevalence-of low HDL-cholesterol in kindreds with a high incidence of myocardial infarction (Breslow 1988), and by the observation of prevented atherosclerosis in transgenic mice overexpressing the human apo A-I gene (Rubin et al. 1991).
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© 1993 Springer-Verlag Berlin Heidelberg
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von Eckardstein, A., Jonas, A., Castro, G., Fruchart, JC., Funke, H., Assman, G. (1993). Structure-Function Relationships of Apolipoprotein A-I Variants . In: Sirtori, C.R., Franceschini, G., Brewer, B.H. (eds) Human Apolipoprotein Mutants III. NATO ASI Series, vol 73. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84634-2_23
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DOI: https://doi.org/10.1007/978-3-642-84634-2_23
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