Influence of phosphatidylcholine molecular species composition on stability of the erythrocyte membrane.

Abstract

Membrane phospholipids comprise an impressive number of different molecular species which differ in their fatty acyl constituents. Obviously, this heterogeneity serves important functional parameters of the membrane, such as its permeability characteristics and the physical state of the lipid bilayer which, in turn, may control the activity of membranebound enzymes. To gain some insight into the impact individual species of a particular phospholipid may have on the structure and function of a membrane, an approach was used which enabled a modification of the phosphatidylcholine (PC) species composition in the membrane of the intact human erythrocyte in vitro, without altering the nature and content of any other membrane constituent (Lange et al., 1980; Kuypers et al., 1984~) . The human erythrocyte was chosen because the composition and organization of its lipid bilayer is known in great detail. PC comprises approximately 30% of the total phospholipid complement of this membrane and is distributed asymmetrically over both halves of the bilayer, 76% is found in the outer leaflet, and 24% in the inner one. The most abundant type of PC species found in the human erythrocyte membrane, accounting for over 70% of its total PC, is that having a saturated fatty acid (either palmitic or oleic acid) at the sn-1 and an unsaturated fatty acid at the sn-2 position of the glycerol backbone. The two major species are ( 1 -palmitoyl,2-oleoyl)and ( l-palmitoyl,2-linoleoyl)-PC, with each accounting for over one-third of this category. The remaining 20-25% of the PC is mainly composed of species containing either two saturated or two unsaturated fatty acyl chains (Op den Kamp et al., 1985). The molecular species compositions of both the outer and inner monolayer pools of PC are almost identical, which might be ascribed to the existence of transbilayer movements of PC molecules. It is worth noting, however, that the rate of these translocations strongly depends on the type of species: half-time values for this process varying from 4 up to 27 h at 37°C (Middelkoop et al., 1986). During the 120 days life span of the human erythrocyte, the composition of its membrane lipids appears to be highly conserved. To a certain extent, this also holds for the fatty acid composition of the phospholipids which, even under extreme variations in dietary fats, show changes that are less pronounced when compared with those that can be induced in the fatty acid pattern of the plasma lipids. However, a PCspecific transfer protein (PC-TP) that can be purified from bovine liver, provides a unique tool for the retailoring of the molecular species composition of PC in intact erythrocytes in vitro. Owing to the specific feature of the PC-TP of mediating a genuine one-for-one exchange of PC molecules (Wirtz & van Deenen, 1977), neither the total amount, nor the composition of the membrane phospholipids is altered this way (Lange et al., 1980; Kuypers et al., 1984~) . When intact