Figure 5

Schematic illustrating albumin bound and free LysoPCs relative to circulating phosphatidylcholine (PC)-containing particles and sPLA2 enzymes. According to current theory, the sPLA2 enzyme "scoots" along the PC vesicle cleaving the A2 fatty acid to produce lysoPC (see text). The desorbed or free lysoPC may be toxic and but this toxicity is neutralized by albumin binding. It is suggested that when excessive lysoPCs are produced during periods of high enzyme activity, they become sPLA2 enzyme inhibitors acting at the point of advancing PC hydrolysis. This configuration would allow for the formation of the Enzyme-Inhibitor-Substrate (ESI) complex, a feature of the uncompetitive inhibition demonstrated in this study. Exogenous lysoPCs may augment this process. It is unclear whether the lysoPC acting as an inhibitor is bound to albumin, but in the present experiments, physiological concentrations of albumin had no discernable effect on the inhibition.