Differential effect of lysophospholipids on activities of human plasma paraoxonase1, either soluble or lipid-bound.
Interaction of paraoxonase1 (PON1) with lysophospholipids was examined with respect to activity regulation and binding property. Paraoxonase activity of purified PON1 was partially inhibited by palmitoyl-lysophosphatidyl-glycerol (palmitoyl-lysoPG) and lysophosphatidylinositol (lysoPI), which had a stimulatory effect on arylesterase and diazoxonase activities. The selective inhibition of paraoxonase activity by palmitoyl-lysoPG, characterized by noncompetitiveness and charge interaction, was also observed with HDL- or dimyristoylphosphatidylcholine (DMPC)-bound PON1. Meanwhile, lysophosphatidylcholine (lysoPC) stimulated all three activities of purified PON1, although it stimulated DMPC-bound or HDL-bound PON1 to a lesser extent. The stimulatory action of lysophospholipids was observed around their CMC, suggesting that micelle formation of lysophospholpids might be involved in the stimulation of PON1 activity. Presumably in support of this, the tryptophan fluorescence intensity of PON1 was increased by lysophospholipids at concentrations required for the stimulation of PON1 activity. Separately, lysoPC stimulation was less remarkable for DMPC-bound PON1 than for either dimyristoylphosphatidylserine (DMPS)- or dimyristoylphosphatidylglycerol-bound PON1, suggesting a tight association between PON1 and DMPC. In support of this, the stimulatory role of apolipoprotein A-I was less prominent for DMPC-bound PON1 than for DMPS-bound PON1. Taken together, these data suggest that the inhibition of paraoxonase activity by lysoPG or lysoPI may be due to binding to a site distinct from the active center, whereas the stimulation by lysophospholipid may be ascribed to the micelle formation around the lipid-associable region of PON1.
Park
Cheon Ho
CH
College of Pharmacy, Chungnam National University, Daejon, Korea.
Nguyen
Su Duy
SD
Kim
Mee Ree
MR
Jeong
Tae-Sook
TS
Sok
Dai-Eun
DE
D016632:Apolipoprotein A-I / Q000378:metabolism; D043303:Aryldialkylphosphatase / Q000097:blood / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D001665:Binding Sites; D004134:Dimyristoylphosphatidylcholine / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005453:Fluorescence; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D012995:Solubility; D014364:Tryptophan / Q000737:chemistry
D016632:Apolipoprotein A-I; D004791:Enzyme Inhibitors; D008055:Lipids; D008081:Liposomes; D008246:Lysophospholipids; C025449:lysophosphatidylinositol; D014364:Tryptophan; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human; D004134:Dimyristoylphosphatidylcholine