Park Cheon Ho, Nguyen Su Duy, Kim Mee Ree, Jeong Tae-Sook, Sok Dai-Eun
College of Pharmacy, Chungnam National University, Daejon, Korea.
Lipids. 2006 Apr;41(4):371-80. doi: 10.1007/s11745-006-5108-4.
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.
就活性调节和结合特性而言，对对氧磷酶1（PON1）与溶血磷脂的相互作用进行了研究。纯化的PON1的对氧磷酶活性受到棕榈酰溶血磷脂酰甘油（棕榈酰溶血PG）和溶血磷脂酰肌醇（溶血PI）的部分抑制，而这两种物质对芳基酯酶和对二氮磷酶活性具有刺激作用。棕榈酰溶血PG对氧磷酶活性的选择性抑制具有非竞争性和电荷相互作用的特征，在与高密度脂蛋白（HDL）或二肉豆蔻酰磷脂酰胆碱（DMPC）结合的PON1中也观察到了这种现象。同时，溶血磷脂酰胆碱（溶血PC）刺激了纯化的PON1的所有三种活性，尽管它对与DMPC结合或与HDL结合的PON1的刺激程度较小。溶血磷脂的刺激作用在其临界胶束浓度（CMC）附近观察到，这表明溶血磷脂的胶束形成可能参与了PON1活性的刺激。据推测，支持这一点的是，在刺激PON1活性所需的浓度下，溶血磷脂会增加PON1的色氨酸荧光强度。另外，溶血PC对与DMPC结合的PON1的刺激作用比对与二肉豆蔻酰磷脂酰丝氨酸（DMPS）或二肉豆蔻酰磷脂酰甘油结合的PON1的刺激作用不那么明显，这表明PON1与DMPC之间存在紧密的结合。支持这一点的是，载脂蛋白A-I对与DMPC结合的PON1的刺激作用比对与DMPS结合得PON1的刺激作用不那么突出。综上所述，这些数据表明，溶血PG或溶血PI对对氧磷酶活性的抑制可能是由于与活性中心不同的位点结合，而溶血磷脂的刺激作用可能归因于PON1脂质结合区域周围的胶束形成。
