Leukotriene B ω-Hydroxylase in Rat Liver Microsomes: Identification as a Cytochrome P-450 That Catalyzes Prostaglandin A1 ω-Hydroxylation, and Participation of Cytochrome b5

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Abstract
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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