TY - JOUR
T1 - Leukotriene b ω-hydroxylase in rat liver microsomes
T2 - Identification as a1 cytochrome P-450 that catalyzes prostaglandin a ω-hydroxylation, and participation of cytochrome b5
AU - Sumimoto, Hideki
AU - Kusunose, Emi
AU - Gotoh, Yoichi
AU - Kusunose, Masamichi
AU - Minakami, Shigeki
PY - 1990/8
Y1 - 1990/8
N2 - 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 LTB ω-hydroxylase as a P-450. The P-450 seems to be also responsible for prostaglandin A, (PGA aj-hydroxylation, but not for laurie aicd ω-hydroxylation. The LTB. ω-hydroxylation is competitively inhibited by PGAI, but not affected by lauric acid. The K, value for PGAI of 38 M agrees with the X value for PGA ω-hydroxylation of 40 μM. LTB inhibits the PGAI ω-hydroxylation by rat liver microsomes in a competitive manner with the K, of 43 pM, which is consistent with the K for the LTB ω-hydroxylation of 42 μM. An antiserum raised against rabbit pulmonary PG ω-hydroxylase (P-450p-2 inhibits slightly the ω-hydroxylations of LTB and PGAI, 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 LTB ω-hydroxylating system, since the reaction is inhibited by an antibody raised against the cytochrome b as well as one raised against the reductase.
AB - 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 LTB ω-hydroxylase as a P-450. The P-450 seems to be also responsible for prostaglandin A, (PGA aj-hydroxylation, but not for laurie aicd ω-hydroxylation. The LTB. ω-hydroxylation is competitively inhibited by PGAI, but not affected by lauric acid. The K, value for PGAI of 38 M agrees with the X value for PGA ω-hydroxylation of 40 μM. LTB inhibits the PGAI ω-hydroxylation by rat liver microsomes in a competitive manner with the K, of 43 pM, which is consistent with the K for the LTB ω-hydroxylation of 42 μM. An antiserum raised against rabbit pulmonary PG ω-hydroxylase (P-450p-2 inhibits slightly the ω-hydroxylations of LTB and PGAI, 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 LTB ω-hydroxylating system, since the reaction is inhibited by an antibody raised against the cytochrome b as well as one raised against the reductase.
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U2 - 10.1093/oxfordjournals.jbchem.a123183
DO - 10.1093/oxfordjournals.jbchem.a123183
M3 - Article
C2 - 2172223
AN - SCOPUS:0025468895
VL - 108
SP - 215
EP - 221
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 2
ER -