Modulation of sulfation and glucuronidation of 1-naphthol in isolated rat liver cells

Schwarz, Leonard

doi:10.1007/bf00303190

Cited by 34 publications

(6 citation statements)

References 23 publications

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“…With higher concentrations of substrate, however, maximal rates were 5-fold greater in livers from fed than in those from starved rats (Fig. 1), confirming earlier work in perfused livers and isolated hepatocytes (Schwartz, 1980;Reinke et al, 1981;Thurman et al, 1981;Aw & Jones, 1984). It is well documented that UDP-glucuronic acid content 3.…”

Section: Discussionsupporting

confidence: 82%

“…Isolated hepatocytes and perfused livers from starved rats have lower rates of glucuronidation than do preparations from fed rats, most likely owing to limited rates of UDP-glucuronic acid synthesis (Reinke et al, 1981). This hypothesis is supported by the observation that addition of carbohydrate stimulates glucuronidation markedly in livers from starved rats (Schwartz, 1980;Reinke et al, 1981;Thurman et al, 1981;Aw & Jones, 1982. The purpose of the present work was to evaluate the importance of UDP-glucuronic acid supply on glucuronidation in periportal and pericentral regions of the liver lobule of the perfused rat liver.…”

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confidence: 89%

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Effect of glucose on 7-hydroxycoumarin glucuronide production in periportal and pericentral regions of the liver lobule

Conway¹,

Kauffman²,

Thurman³

1985

Biochemical Journal

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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.

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Section: Discussionsupporting

confidence: 82%

mentioning

confidence: 89%

Effect of glucose on 7-hydroxycoumarin glucuronide production in periportal and pericentral regions of the liver lobule

Conway¹,

Kauffman²,

Thurman³

1985

Biochemical Journal

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“…In experiments with isolated rat hepatocytes three methods are available in principle to manipulate the sulfotransferase activity ofthe cells. Firstly, it has been demonstrated that there is a rapid equilibrium between medium and cellular inorganic S levels (27)(28)(29). Rat liver cells also have the capacity to generate S by oxidation of the sulfur-containing amino acids methionine and cysteine (28).…”

Section: Resultsmentioning

confidence: 99%

“…Firstly, it has been demonstrated that there is a rapid equilibrium between medium and cellular inorganic S levels (27)(28)(29). Rat liver cells also have the capacity to generate S by oxidation of the sulfur-containing amino acids methionine and cysteine (28). Therefore, considerable S depletion is obtained by keeping cells in medium without S and possible precursors.…”

Section: Resultsmentioning

confidence: 99%

Metabolism of reverse triiodothyronine by isolated rat hepatocytes.

Rooda¹,

Loon²,

Tj³

1987

J. Clin. Invest.

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Reverse triiodothyronine (rT3) is metabolized predominantly by outer ring deiodination to 3,3'-diiodothyronine (3,3'-T2) in the liver. Metabolism of rT3 and 3,3'-T2 by isolated rat hepatocytes was analyzed by Sephadex LH-20 chromatography, high performance liquid chromatography, and radioimmunoassay, with closely agreeing results. Deiodinase activity was inhibited with propylthiouracil (PTU) and sulfotransferase activity by sulfate depletion or addition of salicylamide or dichloronitrophenol. Normally, little 3,3'-T2 production from rT3 was observed, and 1251 was the main product of both 3,13'-'25iT2 and 13',5'-25IlrT3. PTU inhibited rT3 metabolism but did not affect 3,3'-T2 clearance as explained by accumulation of 3,3'-T2 sulfate. Inhibition of sulfation did not affect rT3 clearance but 3,3'-T2 metabolism was greatly diminished. The decrease in I formation from rT3 was compensated by an increased recovery of 3,3'-T2 up to 70% of rT3 metabolized. In conclusion, significant production of 3,3'-T2 from rT3 by rat hepatocytes is only observed if further sulfation is inhibited.

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“…Formation of the cosubstrate for sulphate conjugation, PAPS, depends critically on the availability of inorganic sulphate, and conjugation may be restricted by its depletion (Mulder & Keulemans, 1978;Krijgsheld et al, 1982). Sulphate is depleted by low protein diets and administration of substrates for conjugation but activity can be restored with sodium sulphate or compounds such as cysteine and N-acetylcysteine which are metabolised to inorganic sulphate (Schwartz, 1980;Krijgsheld et a/., 1981;Lin & Levy, 1981). There may also be competition between substrates for sulphate conjugation (Levy & Yamada, 1971).…”

Section: Sulphate Conjugationmentioning

confidence: 99%

Drug conjugation in clinical toxicology

Prescott

1984

Biochemical Society Transactions

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Conjugation is an important mechanism for the rapid inactivation and extensive removal of drugs and poisons from the body, and as such it is of major significance in clinical toxicology. The capacity for conjugation of some drugs is large, but with others, saturation may occur with overdosage or even high therapeutic doses. Glutathione conjugation is an important mechanism of protection against toxicity produced by heavy metals, alkylating agents and some compounds which undergo metabolic activation.

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Modulation of sulfation and glucuronidation of 1-naphthol in isolated rat liver cells

Cited by 34 publications

References 23 publications

Effect of glucose on 7-hydroxycoumarin glucuronide production in periportal and pericentral regions of the liver lobule

Effect of glucose on 7-hydroxycoumarin glucuronide production in periportal and pericentral regions of the liver lobule

Metabolism of reverse triiodothyronine by isolated rat hepatocytes.

Drug conjugation in clinical toxicology

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