Leukotriene B4 metabolism by hepatic cytochrome P-450

Leukotriene B4 (LTB) was found to be metabolized by suspensions of rat liver microsomes in the presence of NADPH and oxygen. The rate of LTB metabolism was also measured in reconstituted systems of both micelles and phospholipid vesicles containing cytochrome P-450-LM2, NADPH cytochrome P-450 reductase, and cytochrome b5. A 1 microM concentration of LTB was metabolized by rat hepatic microsomes at a rate of 4 pmol LTB/min/nmole P-450, and by vesicle and micelle reconstituted systems at 3 pmole/min/nmole P-450-LM2. At this rate a 10 g rat liver exposed to 1 microM LTB can metabolize 30 micrograms per hour. In that the leukotrienes are pharmacologically active at nanomolar concentrations, hepatic metabolism may be an important pathway of leukotriene inactivation.