Development of the Glucuronyltransferase and Sulphotransferase towards 2-Naphthol in Human Fetus

Abstract

The activity of the microsomal glucuronyltransferase (GT) was measured in 34 fetal and 27 adult human livers with 2-naphthol as substrate. The average ( ± SD) enzyme activity was 0.07 ± 0.07 nmol/min/mg protein (fetal) and 7.98 ± 4.19 nmol/min/mg protein (adult) livers. The adult to fetal ratio of the GT activity was 114. The activity of the cytosolic sulphotransferase (ST) was measured with 2-naphthol as substrate in 30 fetal and 23 adult livers. ST activity (mean ± SD) was 0.18 ± 0.12 nmol/min/mg protein (fetal) and 0.63 ± 0.22 nmol/min/mg protein (adult). The adult to fetal ratio of the ST activity was 3.5. The postnatal development of GT is more marked than that of ST. In the fetal livers, the rate of 2-naphthol sulfation correlated (p < 0.01) with the rate of 2-naphthol glucuronidation, whereas they did not correlate in the adult livers. No relationship was observed between the activity of the GT or ST and gestational age. The correlation existing between ST and GT in human fetus might suggest that the two enzymes are under a common developmental pattern which seems to be independent of gestational age. The activity of the GT with morphine as substrate was measured in 25 fetal and 29 adult livers and found to be 0.23 ± 0.20 nmol/ min/mg protein (fetal) and 1.85 ± 0.98 nmol/min/mg protein (adult). Thus, the adult to fetal ratio of morphine glucuronidation was 8. The isoenzyme of the GT catalyzing the conjugation of planar molecules such as 2-naphthol seems to be less developed than that catalyzing the conjugation of bulkier molecules such as morphine in fetus at midgestation.

Embryonic turkey liver: activities of biotransformation enzymes and activation of DNA-reactive carcinogens

“…Enzyme activity levels are expressed in nmoles/minute · gram except for GST activity which is expressed in micromoles/ minute · gram. Values represent the mean ± SEM of four samples per group and analyzed by ANOVA (* p<0.05) embryonic liver are ALD (33 pmoles/min · mg protein; Cresteil et al 1985), EH (48-224 pmoles/min · mg protein; Omiecinski et al 1994) and GLUT (70-340 pmoles/min · mg protein; Leaky et al 1987;Pacifici et al 1989). It is difficult to compare enzyme activities of embryonic and fetal human liver with those of embryonic turkey liver, since most assays utilized to measure enzyme activities in embryonic and fetal human liver involved methods and substrates different from those utilized in our studies.…”

Population clinical pharmacology of children: modelling covariate effects

“…The foetus is capable of metabolising morphine (hepatic enzyme uridine 5′-diphosphate glucuronosyl transferase-2B7, UGT2B7) from 15 weeks gestation [46,47]. The neonate can use sulphate conjugation as an alternative route for substrates, such as morphine or acetaminophen, before glucuronidation matures.…”

Urinary 1-hydroxypyrene and 2-naphthol concentrations in male Koreans

“…In contrast to pyrene, which is absorbed through not only the respiratory tract but also the gastrointestinal tract and skin, naphthalene is mainly absorbed by inhalation (Keimig and Morgan 1986). Absorbed naphthalene undergoes rapid hydroxylation to 1-and 2-naphthol, and conjugates to form more water-soluble derivatives, which are excreted in urine (Paci®ci et al 1989, Tingle et al 1993.…”