Lysophosphatidic acids are new substrates for the phosphatase domain of soluble epoxide hydrolase.
Soluble epoxide hydrolase (sEH) is a bifunctional enzyme that has a C-terminus epoxide hydrolase domain and an N-terminus phosphatase domain. The endogenous substrates of epoxide hydrolase are known to be epoxyeicosatrienoic acids, but the endogenous substrates of the phosphatase activity are not well understood. In this study, to explore the substrates of sEH, we investigated the inhibition of the phosphatase activity of sEH toward 4-methylumbelliferyl phosphate by using lecithin and its hydrolyzed products. Although lecithin itself did not inhibit the phosphatase activity, the hydrolyzed lecithin significantly inhibited it, suggesting that lysophospholipid or fatty acid can inhibit it. Next, we investigated the inhibition of phosphatase activity by lysophosphatidyl choline, palmitoyl lysophosphatidic acid, monopalmitoyl glycerol, and palmitic acid. Palmitoyl lysophosphatidic acid and fatty acid efficiently inhibited phosphatase activity, suggesting that lysophosphatidic acids (LPAs) are substrates for the phosphatase activity of sEH. As expected, palmitoyl, stearoyl, oleoyl, and arachidonoyl LPAs were efficiently dephosphorylated by sEH (Km, 3-7 μM; Vmax, 150-193 nmol/min/mg). These results suggest that LPAs are substrates of sEH, which may regulate physiological functions of cells via their metabolism.
Research Center for Environmental Bioscience and Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda, Japan.
Ami
A
Oguro
Research Center for Environmental Bioscience and Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda, Japan. Electronic address: imaoka@kwansei.ac.jp.
Susumu
S
Imaoka
D002853:Chromatography, Liquid; D004851:Epoxide Hydrolases / Q000378:metabolism*; D006801:Humans; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D013379:Substrate Specificity
D008246:Lysophospholipids; D004851:Epoxide Hydrolases