Cytochrome P-450 Epoxygenase Dependent Formation of Novel Endogenous Epoxyeicosatrienoyl-Phospholipids

Abstract

The steroselective nature of the c/s-epoxyeicosatrienoic acids (EETs) present, in vivo, in rat liver and kidney and human kidney confirmed their biosynthetic origin and established the epoxygenase as an additional member of the arachidonate metabolic cascade (1,2). A functional role for this pathway has been suggested by the potent biological activities attributed to its products (3). A unique feature of the endogenous EETs was their presence, in vivo, esterified to the sn-2 position of several glycerophospholipids (PLs) (2). The EET-PLs were formed endogenously and under normal, physiological conditions (2). In the rat liver, EET-PL formation involves a multistep process initiated by cytochrome P450 stereospecific epoxidation of arachidonic acid, ATP dependent EET activation and EET enantiomer specific EET-CoA lysolipid acylation (2). These results suggested an in vivo role for cytochrome P450 in the biosynthesis of novel phospholipid pools.