METAL-ION STIMULATION AND INHIBITION OF LYSOPHOSPHOLIPASE-D WHICH GENERATES BIOACTIVE LYSOPHOSPHATIDIC ACID IN RAT PLASMA

We found that lysophospholipase D (LPLD) in rat plasma prefers unsatur ated to saturated lysophosphatidylcholines as substrates, generating a biologically active lipid, lysophosphatidic acid, but it does not hyd rolyze diacyl-phospholipids. In this study, this LPLD required a metal ion for activity, Co2+ being the most effective, followed in order by Zn2+ Mn2+, and Ni2+. This metal-ion-stimulated LPLD with unique subst rate specificity, which has not been described previously, was suscept ible to thiol-blocking reagents and serine esterase inhibitors, but no t to a histidine-modifying reagent. Consistent with results using thio l-modifying agents, short-chain fatty aldehydes, secondary products of lipid peroxidation, were found to inhibit LPLD. Addition of dibutylhy droxytoluene or butylhydroxyanisole to the plasma increased the activi ty of this enzyme, probably in a manner independent of its antioxidant activity, since another antioxidant, propyl gallate, was rather inhib itory. These results suggest that rat plasma contains an active LPLD t hat differs in some properties from other members of the known phospho lipase D family detected in animal tissues and body fluids.