Influence of substrate concentration on the phase I and phase II metabolism of 4-methoxybiphenyl by rat isolated hepatocytes

Abstract

1. The metabolism of 4-methoxybiphenyl to 4-hydroxybiphenyl and its sulphate and glucuronic acid conjugates has been studied in rat isolated hepatocytes at various concentrations of 4-methoxybiphenyl. 2. The proportions of metabolites produced remained constant at concentrations of 4-methoxybiphenyl less than 25-50 microM, but at higher concentrations the pattern of metabolism changed, there being proportionally more unconjugated 4-hydroxybiphenyl and its glucuronide, and less 4-hydroxybiphenyl sulphate. 3. The amount of 4-hydroxybiphenyl sulphate produced approached a plateau at the highest level of overall metabolism, whereas the amount of 4-hydroxybiphenyl glucuronide produced was linearly related to the amount of unconjugated 4-hydroxybiphenyl detected. 4. These data are consistent with the view that sulphation acts as a high-affinity, low-capacity pathway, whereas glucuronidation acts as a low-affinity, high-capacity pathway.

1‐hydroxypyrene glucuronide as the major aqueous pyrene metabolite in tissue and gut fluid from the marine deposit‐feeding polychaete Nereis diversicolor

“…Most species have a preferred route of conjugation, but other routes are still available and utilized. Furthermore, the balance between different phase II pathways can depend on the concentration of phase I product delivered [33]. No increase in the number of pyrene conjugates formed was observed when terrestrial isopods were fed a single high dose of pyrene compared to continuous exposure of pyrene for 14 d in the food; however, the relative levels of pyrene metabolites did change [25].…”