Leukotriene B4 .OMEGA.-hydroxylase in rat liver microsomes: Identification as a cytochrome P-450 that catalyzed prostaglandin A1.OMEGA.-hydroxylation, and participation of cytochrome b5.

J-STAGE
  • Sumimoto Hideki
    Department of Biochemistry, Kyushu University School of Medicine
  • Kusunose Emi
    Toneyama Institute for Tuberculosis Research, Osaka City University Medical School
  • Gotoh Yoichi
    Department of Biochemistry, Kyushu University School of Medicine
  • Kusunose Masamichi
    Toneyama Institute for Tuberculosis Research, Osaka City University Medical School
  • Minakami Shigeki
    Department of Biochemistry, Kyushu University School of Medicine

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説明

The ω-hydroxylation of leukotriene B4 (LTB4) by rat liver microsomes requires NADPH and molecular oxygen, suggesting that the hydroxylation is catalyzed by a cytochrome P-450 (P-450)-linked monooxygenase system. The reaction is inhibited by CO, and the inhibition is reversed by irradiation of light at 450 nm in a light-intensity-dependent manner. The extent of the reversal is strongly dependent on the wavelength of the light used, the 450-nm light is most efficient. The finding provides direct evidence for the identification of the LTB4, ω-hydroxylase as a P-450. The P-450 seems to be also responsible for prostaglandin A1 (PGA1) ω-hydroxylation, but not for lauric aicd ω-hydroxylation. The LTB4, ω-hydroxylation is competitively inhibited by PGA1 but not affected by lauric acid. The K1 value for PGA1 of 38 μM agrees with the Km value for PGA1 ω-hydroxylation of 40 μM. LTB4 inhibits the PGA1 ω-hydroxylation by rat liver microsomes in a competitive manner with the K1 of 43 μM, which is consistent with the Km, for the LTB4 ω-hydroxylation of 42 μM. An antiserum raised against rabbit pulmonary PG ω-hydroxylase (P-450p-s) inhibits slightly the ω-hydroxylations of LTB4, and PGA1, while it has stronger inhibitory effect on lauric acid ω-hydroxylation. In addition to NADPH-cytochrome P-450 reductase, cytochrome b5 appears to participate in the LTB4 ω-hydroxylating system, since the reaction is inhibited by an antibody raised against the cytochrome b5 as well as one raised against the reductase.

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