Biosynthesis of platelet-activating factor and enzyme inhibitors

Platelet-activating factor (PAF) is known to be synthesized by either a remodeling or de novo pathway. The enzymes responsible have been extensively studied by a number of laboratories. All evidence indicates the remodeling route is activated during inflammation and other hypersensitivity responses, whereas the de novo pathway is thought to be the source of PAF required for physiological functions. This article provides an update of what is currently known about the enzymatic systems that generate PAF as well as some preliminary findings we have obtained using potential inhibitors of the specific enzymes involved. Recent progress from our laboratory toward understanding the role of the CoA-independent and Co-A dependent transacylases in the formation of lyso-PAF and PAF is summarized.