PMID: 2370851Jul 1, 1990Paper

Unique role of oxygen in regulation of hepatic monooxygenation and glucuronidation

Molecular Pharmacology
Y R WuR G Thurman


The purpose of this study was to evaluate the hypothesis that NADPH supply in intact cells is regulated by oxygen tension. This was accomplished by studying monooxygenation in perfused livers from Ah locus-responsive C57BL/6J mice, where rates of monooxygenation are high. Elevation of flow rate decreases the hepatic O2 gradient and increases O2 delivery to the organ. Under these conditions, rates of p-nitroanisole O-demethylation were 2-3 times higher in perfused livers from fed or fasted mice at high (10 ml/min) compared with normal (5 ml/min) flow rates. Rates of monooxygenation were directly proportional to oxygen tension (half-maximal rates occurred with approximately 400 microM O2). On the other hand, rates were independent of oxygen concentration in isolated microsomes where NADPH was supplied in excess. The decrease in rate due to diminished O2 concentration in the intact organ could not be attributed to hypoxia, because O2 tension in the effluent perfusate exceeded 50 microM even when influent perfusate was saturated with 25% O2 and ATP/ADP ratios were in the normal range. Thus, monooxygenation of p-nitroanisole in perfused mouse liver is dependent on oxygen tension. Similarly, glucuronidation of p-nitrophenol was oxyge...Continue Reading

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