Thiol Methyltransferase in Humans: Development and Tissue Distribution

Abstract

Thiol methyltransferase (EC 2.1.1.9, TMT) activity was measured with 2-mercaptoethanol in the microsomal fraction of 12 placenta and 31 fetal and 33 adult liver specimens. TMT activity (nmol/min incubation/mg protein; mean ± SD) was 0.61 ± 0.25 (placenta), 0.74 ± 0.45 (fetal liver), and 4.51 ± 2.29 (adult liver). TMT activity was also measured in extrahepatic tissues and it was about one order of magnitude lower in fetal lungs, kidney and intestine as compared with the fetal liver. A similar distribution pattern was also observed in adult tissues except that in the kidney TMT activity was one third of the hepatic one. Studies of enzyme kinetics showed that fetal and adult hepatic TMT obeyed non-Michaelis-Menten kinetics when 2-mercaptoethanol was the varying substrate. Average values of Km for the higher and lower affinity phases were 0.03 and 14.05 mmol/l, respectively (fetal liver) and 0.005 and 14.57 mmol/l, respectively (adult liver). This paper shows that TMT develops prenatally and its distribution pattern is consistent with that of other microsomal enzymes, being preferentially associated with the liver both in the human fetus and in adult subject.

Interindividual variability in the N‐sulphation of desipramine in human liver and platelets.

“…Such variability is greater than that described for the O-sulphation of 2-naphthol (Pacifici et al, 1988) and ethinyloestradiol (Temellini et al, 1991) in human liver. This prompted us to characterize further the interindividual variability of DMI N-sulphation in human liver.…”

“…N-ST activity is widely distributed in the body, its average activity in extrahepatic tissues being 2-7 fold lower than that in the liver. The rate of hepatic N-sulphation of DMI showed a 3-4 fold greater interindividual variability than those of 2-naphthol (Pacifici et al, 1988) and ethinyloestradiol (Temellini et al, 1991) O-sulphation. The coefficient of variation for platelet N-ST activity was twice that for hepatic N-ST activity.…”

“…Anderson et al (1981) found a 15-fold variation of platelet O-sulphotransferase activity. This compared with a 5-7-fold variation in its hepatic activity (Pacifici et al, 1988;Temellini et al, 1991).…”

“…The paucity of data on human liver N-and O-sulphotransferases makes it difficult to assess whether these enzymes are under common or different control. The limited evidence available, based on interindividual variability of 2-naphthol (Pacifici et al, 1988) and ethinyloestradiol (Temellini et al, 1991) sulphation, the symmetric frequency distribution histogram of O-sulphotransferase (Temellini et al, 1991) and the higher rate of O-sulphotransferase in ileum than colon (Cappiello et al, 1990b;Pacifici et al, 1989) suggests that O-sulphotransferase and N-ST activity are under independent control. The rates of p-nitrophenol-and dopamine-sulphation measured in 100 human livers do not correlate with the rate of DMI N-ST (unpublished data).…”

“…Sulphation of hydroxy groups has been described in human liver and in blood platelets. The hepatic sulphation of 2-naphthol (Pacifici et al, 1988) and ethinyloestradiol (Temellini et al, 1991) varies over a range of 5 and 7-fold, respectively, whereas, in platelets, the sulphation of 3-methoxy-4-hydroxyphenylglycol (Anderson et al, 1981) and minoxidil (Johnson & Baker, 1987) varies over a range of 15-fold. Sulphation at nitrogen atoms has received little attention although alkyl-and aryl-amines are N-sulphated in rat liver (Iwasaki et al, 1983(Iwasaki et al, , 1986Johnson et al, 1982;Ramaswamy & Jakoby, 1987). The (Iwasaki et al, 1986).…”