Role of group IIa and group V secretory phospholipases A(2) in the metabolism of lipoproteins. Substrate specificities of the enzymes and the regulation of their activities by sphingomyelin.
Although many isoforms of secretory phospholipases A(2) (sPLA(2)) are known to be secreted by various inflammatory cells, and are present in plasma, their role in lipoprotein metabolism is unknown. We studied the in vitro hydrolysis of lipoprotein phospholipids by group IIa and group V sPLA(2), two structurally related enzymes with differing phospholipid specificities. The group V sPLA(2) was about 30 times more efficient than the group IIa enzyme in the hydrolysis of lipoprotein phosphatidylcholine (PC), and both enzymes were more active on high density liporotein (HDL) than on low density lipoprotein (LDL). The lower activity on LDL appears to be due to the higher sphingomyelin (SPH) concentration in this lipoprotein. PC hydrolysis in lipoproteins was stimulated significantly by enzymatic depletion of their SPH. The hydrolysis of PC in liposomes was inhibited by the incorporation of SPH, and this inhibition was reversed by treatment with sphingomyelinase. The incorporation of ceramide, on the other hand, stimulated the sPLA(2) activity significantly. Unlike most sPLA(2), which show no fatty acid preference, group V sPLA(2) released disproportionately more linoleate, and less arachidonate from lipoproteins. These studies show that group V sPLA(2) is physiologically more important than group IIa enzyme in lipoprotein metabolism, that the sPLA(2) activities are regulated by sphingomyelin and ceramide, and that the pathological effects of sPLA(2) may not be mediated through stimulation of eicosanoid synthesis.
Gesquiere
Laurence
L
Department of Medicine, Rush Medical College, Chicago, Illinois 60612, USA.
Cho
Wonhwa
W
Subbaiah
Papasani V
PV
D000818:Animals; D017815:Elapidae; D054501:Group II Phospholipases A2; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008074:Lipoproteins / Q000378:metabolism*; D008075:Lipoproteins, HDL / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D013109:Sphingomyelins / Q000494:pharmacology; D013379:Substrate Specificity
D007527:Isoenzymes; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010743:Phospholipids; D013109:Sphingomyelins; D010741:Phospholipases A; D054501:Group II Phospholipases A2