Binding continued lipoprotein

An alternative metabolic pathway is available to a VLDL. in this process, the particle loses its apo E as it matures to an IDL. Without apo E, the particle is not efficiently taken up by the liver but continues to circulate in the bkKdstream. Continued removal of TGs from an IDL produces a lipoprotein particle called an LDL that is enriched in cholesteryl esters. After conversion to an LDL, only a single apo B molecule remains on the surface of the particle. This protein binds only relatively weakly to an LDL receptor. Consequently, LDLs have residence times in the circulation of about 3 days. Eventually, LDLs are taken up by various tissues. The receptor that binds an LDL, called an LDL receptor, is similar, or perhaps identical, to the receptors that bind circulating IDLs and mediate their entry into hepatocytes. 

The use of vacutainer tubes and heparin was shown to alter the determination of protein binding. Heparin was shown to decrease the plasma binding of certain drugs including phenytoin, propranolol, lidocaine, diazepam, quinidine, and verapamil. This is also an in vitro artifact attributable to continued ex vivo activity of the lipoprotein lipase enzyme and accumulation of fatty acids in the blood collection tube. 

Fig. 1. Oxidation hypothesis. Proposes minimally modified LDL is formed due to oxidation in the arterial intimal space. This LDL can still be taken up by the LDL receptor, but minimally modified LDL promotes release of proinflammatory mediators from monocytes and acts as a monocyte inhibition factor (MIF), reducing the motility of monocytes and thus leading to recruitment of macrophages (J4, W9). Macrophages further oxidize LDL (OxLDL), release inflammatory mediators, and rapidly take up OxLDL and other lipoproteins via the unregulated scavenger receptor that binds modified apo B to form lipid-laden foam cells. OxLDL is cytotoxic to a variety of cells in culture and may disrupt endothelial tissue, causing the release of inflammatory mediators and the entry of more LDL into the intimal space. Continued accumulation of monocytes and their differentiation into macrophages leads to a vicious cycle (J4, W9). Adapted from reference J4.

Understanding of the biological activities of oxidatively modified lipids depends, at least in part, on knowledge of the receptors to which they bind and the signaling pathways that are affected. Research over the last three decades has enabled the identification of several important receptors, although it is likely that others will continue to be discovered. Much work has been carried out on the platelet activation factor (PAF) receptor, which recognizes a number of truncated oxidized phospholipids (McIntyre, 2012). A lipoprotein-associated phospholipase A2, PAF-acetylhydrolase, can hydrolyze oxidized chains at the sn-2 position of phospholipids... 

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