Food restriction stimulates conjugation of p-nitrophenol in perfused rat liver.
Rates of conjugation of p-nitrophenol were studied in livers from normal and food-restricted rats perfused with either p-nitroanisole or p-nitrophenol. Female Sprague-Dawley rats had ad libitum access to a Purina 5001 nonpurified diet (control) or were given 65% of the intake of controls for 3 weeks. Livers were perfused with oxygenated Krebs-Henseleit buffer using a nonrecirculating system. Maximal rates of conjugation of p-nitrophenol, generated either from the O-demethylation of p-nitroanisole (200 microM) or from the infusion of p-nitrophenol (70 microM), were elevated significantly nearly twofold by food restriction. Thus, food restriction stimulates conjugation in the intact liver cell. Specifically, rates of conjugation were increased from 2.1 +/- 0.2 to 3.7 +/- 0.4 and from 3.3 +/- 0.6 to 5.8 +/- 0.5 mumol/g/h when 200 microM p-nitroanisole or 70 microM p-nitrophenol were infused, respectively. On the other hand, rates of conjugation were not affected by food restriction when low concentrations of p-nitroanisole (50 microM) or p-nitrophenol (20 microM) were infused. Further, food restriction did not alter rates of conjugation in isolated microsomes supplemented with excess UDPGA. Interestingly, both UDP-glucose and UDP-glucuronic acid were increased significantly in liver extracts from food-restricted rats when livers were perfused with high but not low concentrations of p-nitrophenol. Under these conditions, the increase in UDP-glucuronic acid was threefold. Moreover, food restriction increased carbohydrate release from the liver about twofold. Glycogen content was also increased significantly in liver extracts from 8.4 +/- 1.9 to 60.4 +/- 13.8 mmol/kg wet weight by food restriction. Taken together, these data support the hypothesis that food restriction stimulates conjugation of p-nitrophenol concentrations by increasing the supply of the pivotal cofactor UDP-glucuronic acid from carbohydrate reserves (e.g., glycogen).
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Department of Pharmacology, University of North Carolina at Chapel Hill 27599-7365, USA.
Kauffman
F C
FC
Thurman
R G
RG
D000818:Animals; D002241:Carbohydrates / Q000032:analysis; D005260:Female; D005508:Food Deprivation / Q000502:physiology*; D014453:Glucuronosyltransferase / Q000032:analysis; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D009596:Nitrophenols / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014535:Uridine Diphosphate Glucuronic Acid / Q000494:pharmacology
D002241:Carbohydrates; D009596:Nitrophenols; D014535:Uridine Diphosphate Glucuronic Acid; D014453:Glucuronosyltransferase; C024836:4-nitrophenol