Reaction of Phosphatidylcholine Hydroperoxide in Human Plasma: The Role of Peroxidase and Lecithin:Cholesterol Acyltransferase

Abstract

In order to elucidate the reason why phosphatidylcholine hydroperoxide is unstable in human plasma, 1-palmitoyl-2-linoleoylphosphatidylcholine hydroperoxide (PLPC-OOH) was incubated aerobically in human plasma at 37°C, and its decomposition products were measured. The major product was the corresponding alcohol (PLPC-OH) and this reduction probably occurred by an enzymatic process since no acceleration in ascorbate depletion and no significant decrease in other plasma antioxidants were observed upon addition of PLPC-OOH. Cholesteryl linoleate hydroperoxide and its alcohol (Ch18:2-OH) were also detected as minor products. Similarly, 1-stearoyl-2-arachidonoylphosphatidylcholine hydroperoxide gave its alcohol (SAPC-OH) as a major product and cholesteryl arachidonate hydroperoxide and its hydroxide (Ch20:4-OH) as minor products. These oxidized cholesteryl esters are likely to be produced by the action of lecithin:cholesterol acyltransferase (LCAT) present in high-density lipoprotein (HDL) since (a) incubation of PLPC-OH and SAPC-OH in human plasma gave Ch18:2-OH and Ch20:4-OH, respectively, (b) isolated human HDL converted PLPC-OH to Ch18:2-OH and SAPC-OH to Ch20:4-OH, while isolated human low-density lipoprotein was inactive for this conversion, and (c) formation of oxidized cholesteryl esters in plasma and HDL was inhibited by the LCAT inhibitor 5,5′-dithiobis(2-nitrobenzoic acid). A possible beneficial role of LCAT for converting phosphatidylcholine hydroperoxide to cholesteryl ester hydroperoxide is also discussed.