THE DAMAGE TO PHOSPHOLIPIDS CAUSED BY FREE-RADICAL ATTACK ON GLYCEROLAND SPHINGOSINE BACKBONE

The effect of gamma-radiation on aqueous solutions of saturated phosph olipids, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dipal mitoyl-sn-glycero-3-phosphoglycerol (DPPG), 1-palmitoyl-2-lyso-sn-glyc ero-3-phosphocholine (lysoPC), and bovine brain sphingomyelin (SM) has been investigated. It is shown that the phospholipids with an OH grou p in beta-position to the P-O bond (DPPG and lysoPC), or to the amide bond (SM), undergo a free radical fragmentation. As a result of such f ragmentation, stearoylamide, palmitoxyacetone and phosphatidic acid ar e formed from SM, lysoPC and DPPG, respectively. In parallel with the formation of hydrophobic fragments, an accumulation of hydrophilic spe cies such as oxyacetone and phosphocholine in the irradiated DPPG and lysoPC dispersions was observed. On the basis of the data obtained for free radical transformation of phospholipids and their simplest analo gs, such as glycero-1-phosphate, triacetin and 1,2-isopropylidene glyc erol, it is suggested that the fragmentation of the radicals derived f rom the above compounds proceed by a concerted mechanism through a fiv e-membered transition state. The accumulation of hydrophobic fragments in phospholipid membranes is shown to influence the temperature and c o-operativity of the 'gel-to-liquid crystal' phase transition. An assu mption is made that the fragmentation of phospholipids caused by free radical attack on the hydrophilic moiety, along with lipid peroxidatio n, may constitute principal mechanisms of radiation-induced damage of biological membranes.