6533b82efe1ef96bd129291d

RESEARCH PRODUCT

Interrelationship between demethylation of p-nitroanisole and conjugation of p-nitrophenol in rat liver

subject

description

The metabolism of p-nitroanisole (pNA) and p-nitrophenol (pNP) was studied in isolated rat livers perfused with a hemoglobin-free medium. The activity and viability of the surviving organ was tested by recording pH, “arterial” and “venous” oxygen tension as well as the disappearance of added pNP. pNA is converted to its primary metabolite pNP which, in turn, is excreted into the perfusion medium as conjugates. The coordination of pNA oxidation and the conjugation reactions of pNP were investigated. When 50 μM pNA is added as substrate 0.4±0.1 nmoles×ml−1×(g liver)−1 are excreted as pNP-glucuronide and 3.5±0.2 nmoles×ml−1×(g liver)−1 as the sulphate within 90 min. When pNP itself (50 μM) is the substrate there is a large increase in the glucuronide/sulphate ratio after 50 min to 2.1±0.2 nmoles×ml−1×(g liver)−1 pNP-glucuronide and 2.5±0.3 nmoles×ml−1×(g liver)−1 sulphate. It is concluded that the concentration of pNP in the liver cell determines the type of conjugate discharged. If the pNP concentration is high as in perfusion with pNP itself there is roughly equal formation of glucuronide and sulphate. If pNP concentration is low as in perfusion with its precursor pNA, sulphation prevails very markedly. A possible enzymatic explanation for this finding is discussed. Small, but detectable, quantities of pNP glucoside were found in the medium after perfusion with either pNA or pNP.