Lipid Transport by Apolipoprotein AI: Structure and Function

Autor: E. L. Gong, A. V. Nichols, A. R. Tall
Rok vydání: 1993
Předmět:
Zdroj: Human Apolipoprotein Mutants III ISBN: 9783642846366
Popis: Numerous epidemiologic studies have established a strong inverse relationship between plasma HDL levels and coronary heart disease (CHD) (Miller, 1987). Recent studies suggest that factors influencing levels and metabolism of HDL include both the composition and size of HDL and the fractional catabolic rates of apoAl or apoAll (Brinton et al., 1991). Factors modulating HDL composition and size include lipid transfer proteins (cholesteryl ester transfer protein {CETP} and phospholipid transfer protein {PLTP}) as well as enzymes, such as lecithin:cholesterol acyltransferase {LCAT} and lipases, hepatic triglyceride lipase {HTGL} and lipoprotein lipase {LPL}. Like mature HDL in human plasma, HDL precursors (designated as nascent HDL or nHDL) are also potentially subject to the above modulating agents. However, except for LCAT little is known what effect these factors may have on the structural and metabolic properties of the precursor particles or how such remodeling may influence the channeling of precursors towards specific HDL subpopulations in human plasma. LCAT-mediated transformation of apoAl-containing discoidal analogs of precursor nHDL to HDL-like products is characterized by a strong positive correlation between the size of the precursor particles and the size of their core-containing transformation products (Figure 1) (Nichols, 1990). Thus, modulation-induced change in size of nHDL particles by transfer proteins or enzymes would be expected to correspondingly shift the size of their LCAT-transformation products. In view of the association between HDL level and HDL particle size and composition, reduction in nHDL size may contribute to lower HDL levels and increased risk of CHD. Since nHDL lack core lipids and consist almost exclusively of phospholipid, unesterified cholesterol and apolipoproteins, their remodeling mainly involves phospholipid depletion as facilitated by CETP and PLTP and phospholipid lipolysis as facilitated by HTGL.
Databáze: OpenAIRE