Metabolism of chloramphenicol by glutathione S-transferase in human fetal and neonatal liver.
The glutathione S-transferases of human fetal and neonatal liver catalyse the conjugation of glutathione with chloramphenicol at a low but measurable rate. The highest rates were 1.30 nmol/min/mg protein in a preterm neonate of 26 weeks of gestation and 1.11 nmol/min/mg in a fetus of 22 weeks of gestation, while the lowest measurable was 0.1 nmol/min/mg in a fetus of 17 weeks of gestation. The activity did not correlate with gestational age, but appeared dependent on the concentration of glutathione in the reaction mixture. The rate rose by a factor of three, from 0.39 nmol/min/mg protein with no added glutathione to 1.24 nmol/min/mg with 2 mumol/ml added to the reaction mixture. Chloramphenicol-aldehyde was detectable in the reaction mixture when a liver extract was incubated with glutathione but the proposed intermediate, glutathione-chloramphenicol, could not be demonstrated. Differences in activity with chloramphenicol or a model substrate, under varying conditions, indicate that different isoenzymes are concerned with the conjugation of glutathione to the two substrates. These data support the hypothesis that when glucuronide conjugation is depressed by immaturity, chloramphenicol is metabolised via other pathways.
Holt
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Karim Centre for Meningitis Research, RPMS Institute of Obstetrics and Gynaecology, Queen Charlotte's and Chelsea Hospital, London, UK.
Hurley
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Harvey
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D000447:Aldehydes / Q000378:metabolism; D002701:Chloramphenicol / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004137:Dinitrochlorobenzene / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005865:Gestational Age; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000196:embryology* / Q000201:enzymology*
D000447:Aldehydes; D004137:Dinitrochlorobenzene; D002701:Chloramphenicol; D005982:Glutathione Transferase; D005978:Glutathione