Effect of Glucose on 7-hydroxycoumarin Glucuronide Production in Periportal and Pericentral Regions of the Liver Lobule

Overview

Journal Biochem J

Specialty Biochemistry

Date 1985 Mar 15

PMID 3985943

Authors

J G Conway

F C Kauffman

R G Thurman

Affiliations

Soon will be listed here.

Abstract

The effect of starvation and glucose addition on glucuronidation was assessed in sublobular regions of the lobule in perfused livers from phenobarbital-treated rats. Fibre-optic micro-light guides were placed on periportal and pericentral areas on the surface of livers to monitor the fluorescence (excitation 366 nm, emission 450 nm) of free 7-hydroxycoumarin from the tissue surface. After infusion of 7-hydroxycoumarin (80 microM) under normoxic conditions, steady-state increases in fluorescence were reached in 6-8 min in both regions. Subsequently, the formation of non-fluorescent 7-hydroxycoumarin glucuronide was inhibited completely by perfusion with N2-saturated perfusate containing 20 mM-ethanol. The difference in fluorescence between anoxic and normoxic perfusions was due to glucuronidation under these conditions. In livers from fed rats, rates of glucuronidation in periportal and pericentral regions of the liver lobule were 8 and 19 mumol/h per g, respectively. In contrast, rates of glucuronidation were 3 and 9 mumol/h per g, respectively, in periportal and pericentral regions of livers from starved rats. Infusion of glucose (20 mM) had no effect on rates of glucuronidation in livers from fed rats; however, glucose increased rates of glucuronidation rapidly (half-time, t0.5 = 1.5 min) in periportal and pericentral regions to 7 and 17 mumol/h per g, respectively in livers from starved rats. These results indicate that the rapid synthesis of the cofactor UDP-glucuronic acid derived from glucose is an important rate-determinant for glucuronidation of 7-hydroxycoumarin in both periportal and pericentral regions of livers from starved rats.

References

Marshall W, McLean A . The effect of oral phenobarbitone on hepatic microsomal cytochrome P-450 and demethylation activity in rats fed normal and low protein diets. Biochem Pharmacol. 1969; 18(1):153-7. DOI: 10.1016/0006-2952(69)90020-3. View

DeBaun J, Smith J, Miller E, Miller J . Reactivity in vivo of the carcinogen N-hydroxy-2-acetylaminofluorene: increase by sulfate ion. Science. 1970; 167(3915):184-6. DOI: 10.1126/science.167.3915.184. View

Crisp D, Pogson C . Glycolytic and gluconeogenic enzyme activities in parenchymal and non-parenchymal cells from mouse liver. Biochem J. 1972; 126(4):1009-23. PMC: 1178509. DOI: 10.1042/bj1261009. View

Scholz R, Hansen W, Thurman R . Interaction of mixed-function oxidation with biosynthetic processes. 1. Inhibition of gluconeogenesis by aminopyrine in perfused rat liver. Eur J Biochem. 1973; 38(1):64-72. DOI: 10.1111/j.1432-1033.1973.tb03034.x. View

JOLLOW D, Thorgeirsson S, Potter W, Hashimoto M, Mitchell J . Acetaminophen-induced hepatic necrosis. VI. Metabolic disposition of toxic and nontoxic doses of acetaminophen. Pharmacology. 1974; 12(4-5):251-71. DOI: 10.1159/000136547. View

Dileepan K, WAGLE S, Hofmann F, Decker K . Distribution profile of glucokinase and hexokinase in parenchymal and sinusoidal cells of rat liver during development. Life Sci. 1979; 24(1):89-95. DOI: 10.1016/0024-3205(79)90284-4. View

Felsher B, Carpio N, VanCouvering K . Effect of fasting and phenobarbital on hepatic UDP-glucuronic acid formation in the rat. J Lab Clin Med. 1979; 93(3):414-27. View

Moldeus P, Andersson B, Gergely V . Regulation of glucuronidation and sulfate conjugation in isolated hepatocytes. Drug Metab Dispos. 1979; 7(6):416-9. View

Ji S, Lemasters J, Thurman R . A non-invasive method to study metabolic events within sublobular regions of hemoglobin-free perfused liver. FEBS Lett. 1980; 113(1):37-42. DOI: 10.1016/0014-5793(80)80489-3. View

10.

Schwarz L . Modulation of sulfation and glucuronidation of 1-naphthol in isolated rat liver cells. Arch Toxicol. 1980; 44(1-3):137-45. DOI: 10.1007/BF00303190. View

11.

Reinke L, Belinsky S, Evans R, Kauffman F, Thurman R . Conjugation of p-nitrophenol in the perfused rat liver: the effect of substrate concentration and carbohydrate reserves. J Pharmacol Exp Ther. 1981; 217(3):863-70. View

12.

Pang K, Terrell J . Conjugation kinetics of acetaminophen by the perfused rat liver preparation. Biochem Pharmacol. 1981; 30(14):1959-65. DOI: 10.1016/0006-2952(81)90206-9. View

13.

Thurman R, Reinke L, Belinsky S, Evans R, Kauffman F . Co-regulation of the mixed-function oxidation of p-nitroanisole and glucuronidation of p-nitrophenol in the perfused rat liver by carbohydrate reserves. Arch Biochem Biophys. 1981; 209(1):137-42. DOI: 10.1016/0003-9861(81)90265-4. View

14.

Koster H, Halsema I, Scholtens E, Knippers M, Mulder G . Dose-dependent shifts in the sulfation and glucuronidation of phenolic compounds in the rat in vivo and in isolated hepatocytes. The role of saturation of phenolsulfotransferase. Biochem Pharmacol. 1981; 30(18):2569-75. DOI: 10.1016/0006-2952(81)90584-0. View

15.

Singh J, Schwarz L . Dependence of glucuronidation rate on UDP-glucuronic acid levels in isolated hepatocytes. Biochem Pharmacol. 1981; 30(23):3252-4. DOI: 10.1016/0006-2952(81)90528-1. View

16.

Price V, JOLLOW D . Increased resistance of diabetic rats to acetaminophen-induced hepatotoxicity. J Pharmacol Exp Ther. 1982; 220(3):504-13. View

17.

Fischer W, Ick M, Katz N . Reciprocal distribution of hexokinase and glucokinase in the periportal and perivenous zone of the rat liver acinus. Hoppe Seylers Z Physiol Chem. 1982; 363(4):375-80. DOI: 10.1515/bchm2.1982.363.1.375. View

18.

Aw T, Jones D . Secondary bioenergetic hypoxia. Inhibition of sulfation and glucuronidation reactions in isolated hepatocytes at low O2 concentration. J Biol Chem. 1982; 257(15):8997-9004. View

19.

Kashiwagi T, Ji S, Lemasters J, Thurman R . Rates of alcohol dehydrogenase-dependent ethanol metabolism in periportal and pericentral regions of the perfused rat liver. Mol Pharmacol. 1982; 21(2):438-43. View

20.

Mulder G, Meerman J . Sulfation and glucuronidation as competing pathways in the metabolism of hydroxamic acids: the role of N,O-sulfonation in chemical carcinogenesis of aromatic amines. Environ Health Perspect. 1983; 49:27-32. PMC: 1569136. DOI: 10.1289/ehp.834927. View