Evaluation of sulfate esters and glucuronides by enzymatic means

Roy, A.B.

doi:10.1016/0003-2697(87)90193-x

Cited by 13 publications

(1 citation statement)

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“…No cleavage of the gluc- uronide occurred in the absence of enzyme. The enzymatic cleavage of the glucuronide was inhibited by 10 mM saccharic acid 1,4-lactone (Figure 3C), which is a competitive inhibitor of 3-glucuronidase (17). The complexity of the 19F NMR spectrum of 2-chloro-2,2-difluoroethyl glucuronide, which is characterized by two Vhf = H.3 Hz triplets separated by 4 Hz (Figures 2 and 3), can be explained by second-order spectral interactions (21).…”

Section: Resultsmentioning

confidence: 96%

Metabolism of the hydrochlorofluorocarbon 1,2-dichloro-1,1-difluoroethane

Harris¹,

Anders²

1991

Chem. Res. Toxicol.

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1,2-Dichloro-1,1-difluoroethane (HCFC-132b) is a potential substitute for some ozone-depleting chlorofluorocarbons and a model for other 1,1,1,2-tetrahaloethanes under consideration as chlorofluorocarbon substitutes. Male Fischer 344 rats were given 10 mmol/kg HCFC-132b dissolved in corn oil by intraperitoneal injection. An NMR assay for covalent binding of HCFC-132b metabolites to liver proteins was negative, whereas binding was observed in halothane-treated rats. Total urinary metabolites excreted by rats given HCFC-132b during the first 24 h amounted to 1.8 +/- 0.1% of the injected dose, as determined by 19F NMR. During the first 6 h, metabolites of HCFC-132b corresponding to 2-chloro-2,2-difluoroethyl glucuronide, unknown metabolite A, chlorodifluoroacetic acid, and chlorodifluoroacetaldehyde hydrate [both free and conjugated (unknown metabolite B)] were excreted in urine in the approximate ratio 100:9:3:7, respectively. Metabolite A is apparently an O-conjugate of 2-chloro-2,2-difluoroethanol; unconjugated 2-chloro-2,2-difluoroethanol was not detected in urine. The 19F NMR spectrum of metabolite B indicates the formation of a hemiacetal of chlorodifluoroacetaldehyde. Repeated exposure of rats to HCFC-132b significantly increased both the rate of chlorodifluoroacetic acid excretion and the relative fraction of the HCFC-132b dose excreted as chlorodifluoroacetic acid in urine. Incubation of HCFC-132b with rat hepatic microsomes yielded chlorodifluoroacetaldehyde hydrate as the only fluorinated product. The in vitro metabolism of HCFC-132b was increased in microsomes from pyridine-treated rats as compared with control rats, and HCFC-132b metabolism was inhibited by p-nitrophenol, indicating that the cytochrome P-450 isoform IIE1 is largely responsible for the initial hydroxylation of HCFC-132b.

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Section: Resultsmentioning

confidence: 96%