1. The activities of the ethoxycoumarin O-deethylase (ECOD), epoxide hydrolase (EH), UDP-glucuronyl transferase (GT), glutathione S-transferase (GST), acetyl transferase (AT) and sulphotransferase (ST) were measured in 6 liver, 8 lung, 8 kidney, 8 intestinal mucosa and 22 urinary bladder mucosa specimens from human subjects. EH and GT were studied with styrene oxide and 1-naphthol, respectively, as substrates, GST, AT and ST were studied with benzo(a)pyrene-4,5-oxide, p-aminobenzoic acid and 2-naphthol, respectively. 2. The enzyme activities were detectable at significant rates in liver, lungs, kidneys and gut. In urinary bladder, EH, GT, GST and ST only were detectable. The liver catalyzed the various reactions at higher rates than did other tissues. 3. Of the extrahepatic tissues, the intestinal mucosa contained the highest activities of AT (50% of liver) and ST (30% of liver), whereas kidneys contained the highest activity of GT (50% of liver) and GST (80% of liver). GST was the enzyme with the widest tissue distribution.
Acetyltransferase with p-aminobenzoic acid (PABA) as substrate was investigated in the cytosolic fraction of the placenta, liver, adrenals, lungs, kidneys, intestine from human fetuses and the liver, lungs, kidneys and intestinal mucosa from adult subjects. All tissue specimens assayed catalyzed the acetylation of PABA at a significant rate. The activity (expressed as nmol of product formed/min/mg protein; mean ± SE) was 1.10 ± 0.59 in the fetal liver, 0.66 ± 0.04 in the placental and 3.87 ± 0.53 in the adult liver cytosol. Among the fetal tissues, the adrenals had the highest (2.36 ± 0.78) and the gut the lowest activity (0.71 ± 0.11). The acetyltransferase activity (mean ± SE) in the lungs, kidneys and intestinal mucosa from adult subjects was 1.19 ± 0.15; 1.34 ± 0.04 and 3.80 ± 0.34, respectively.
Sulfotransferase with 2-naphthol as substrate was investigated in the cytosolic fraction of human fetal liver, lungs, kidneys, adrenal glands, intestine and placenta and also in liver, lungs, kidneys, intestinal and urinary bladder mucosa from human adult subjects. All tissue specimens assayed catalyzed the sulfation of 2-naphthol at a significant rate. The activity (expressed as pmole per minute per milligram protein; mean ± SD) was 211 ± 197 (n = 46) fetal liver; 22 ± 12 (n = 29) placenta; 625 ± 205 (n = 42) human adult liver. In fetal kidneys (576 ± 177; n = 6) and gut (558 ± 293; n = 6) the activity was twice as high as in liver. In the lungs (273 ± 125; n = 6) and in the adrenals (174 ± 119; n = 19) the sulfotransferase activity was comparable with the hepatic one. In human adult extrahepatic tissues the highest activity was found in the intestinal mucosa (153 ± 49; n = 4) and the lowest one in the urinary bladder mucosa (16 ± 4; n = 4). This paper shows that the sulfotransferase has a wide distribution in the human fetus and the distribution pattern of this enzyme is different in the human fetus and adult subject.
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.
Glutathione S-transferase (GST) was investigated with benzo(a)pyrene-4,5-oxide (BPO) as substrate in tissue specimens from 26 fetal and 27 adult livers and 27 placentas. The average (+/- SEM) of GST activity in the cytosol was 1.80 +/- 0.18 (fetal liver), 3.05 +/- 0.30 (adult liver) and 1.18 +/- 0.07 (placenta) nmol/min/mg. GST was also investigated in human fetal and adult lungs, kidneys and gut. In these tissues the average (+/- SEM) GST activity ranged between 0.71 +/- 0.12 (adult intestine) and 2.11 +/- 0.18 (fetal lungs) nmol/min/mg. Whereas in the fetal liver the conjugation of BPO was catalyzed at a rate of about two-thirds of the adult rate, similar or higher GST activities were found in the fetal non-hepatic tissues as compared to the adult organs. No correlation was found between the activity of the GST in fetal liver and placenta and the gestational age (11-25 weeks). GST develops before the 11th week of gestation and it does not undergo changes during the mid-gestation. No correlation was found between GST activity in adult liver and age (32-70 years).
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