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 unsaturated to saturated lysophosphatidylcholines as substrates, generating a biologically active lipid, lysophosphatidic acid, but it does not hydrolyze 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 substrate specificity, which has not been described previously, was susceptible to thiol-blocking reagents and serine esterase inhibitors, but not to a histidine-modifying reagent. Consistent with results using thiol-modifying agents, short-chain fatty aldehydes, secondary products of lipid peroxidation, were found to inhibit LPLD. Addition of dibutylhydroxytoluene or butylhydroxyanisole to the plasma increased the activity of this enzyme, probably in a manner independent of its antioxidant activity, since another antioxidant, propyl gallate, was rather inhibitory. These results suggest that rat plasma contains an active LPLD that differs in some properties from other members of the known phospholipase D family detected in animal tissues and body fluids.
Tokumura
A
A
Faculty of Pharmaceutical Sciences, The University of Tokushima, Japan. tokumura@ph.tokushima-u.ac.jp
Miyake
M
M
Yoshimoto
O
O
Shimizu
M
M
Fukuzawa
K
K
D008243:1-Acylglycerophosphocholine O-Acyltransferase / Q000097:blood / Q000187:drug effects; D000447:Aldehydes / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002412:Cations; D002614:Chelating Agents / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008246:Lysophospholipids / Q000097:blood* / Q000378:metabolism; D008297:Male; D008670:Metals / Q000097:blood / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000097:blood / Q000187:drug effects* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000099189:Lysophospholipase D
D008243:1-Acylglycerophosphocholine O-Acyltransferase; D000447:Aldehydes; D000975:Antioxidants; D002412:Cations; D002614:Chelating Agents; D004492:Edetic Acid; D004533:Egtazic Acid; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D008670:Metals; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D