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Sulphotransferase (ST) is a family of enzymes responsible for metabolism and detoxication of endobiotics and xenobiotics. We investigated the hepatic acinar distribution of three sulphotransferases: phenol sulphotransferase (PST), oestrogen sulphotransferase (EST), and hydroxysteroid sulphotransferase (HST) in male and female rat livers by measurement of enzyme activities in isolated periportal and perivenous hepatocytes. The distribution was confirmed by immunohistochemistry. EST activity was located predominantly in the perivenous hepatocytes in male rats but not in female rats, where residual activity is catalysed by another ST. HST activity was not significantly different in periportal and perivenous hepatocytes in either male or female rats. For PST, a more widespread distribution was observed, with slight predominance in the periportal regions. The results indicate heterogeneous distribution of ST isoenzymes in the periportal and perivenous hepatocytes isolated from male and female rat livers. BIOCHEM PHARMACOL 51; 3: 369–374, 1996.

1 Phenol- and catechol- sulphotransferase activities were measured with p-nitrophenol and dopamine as substrates in platelets obtained from 100 newborns and 100 healthy adults. 2 Mean +/- (s.d.) estimates of catechol sulphotransferase activity were 7.07 +/- 5.93 (adult) and 13.3 +/- 6.42 (newborn) pmol min(-1) mg(-1) protein, respectively (P < 0.001). The coefficients of variation were 84% (adult) and 48% (newborn). The frequency distribution of sulphotransferase activity was symmetric and did not deviate significantly from normality in newborn platelets, but was positively skewed in adult platelets. 3 Mean +/- (s.d.) estimates of phenol sulphotransferase activity were 3.01 +/- 3.21 (adult) and 4.80 +/- 4.34 (newborn) pmol min(-1) mg(-1), respectively (P < 0.001). The coefficients of variation were 107% (adult) and 90% (newborn). The frequency distribution of sulphotransferase activity was positively skewed in both newborn and adult platelets. 4 Since sulphotransferase activity in platelets is well-expressed at birth and a prenatal development of sulphotransferase has been described in mid-gestational human foetal liver, the newborn should be able to sulphate drugs.

Phenol sulphotransferase (PST) activity in rat platelet cytosol for p-nitrophenol (PNP) sulphation was found to have a similar dependence on PNP concentration and thermostability to that in rat liver cytosol. The activities of PST isoenzyme for the sulphation in the μM range of PNP in rat platelets and rat liver were significantly correlated. Thus, measurement of PST activity in platelets could be a useful and practical method for predicting this activity in liver.

Arylsulphatase II of Aspergillus oryzae exhibits both hydrolytic and sulphotransferase activities. The kinetic data suggest the formation of an intermediate covalent enzyme-sulphate complex with transfer of sulphate from donor to acceptor proceeding via a Ping Pong mechanism. The unusual kinetic behaviour when 2-hydroxy-5-nitrophenyl sulphate is the substrate is also consistent with this mechanism.

Phenol sulphotransferase from cat and rabbit liver cytosol has been investigated using 4-nitrophenylsulphate as primary sulphate donor. The first stage of the reaction involves sulphation of cofactor adenosine 3',5'-diphosphate to adenosine 3'-phosphate 5'-phosphosulphate, which in turn acts as sulphate donor for other phenolic acceptors. Adenosine 3',5'-diphosphate is regenerated in this second stage, so that the overall reaction is a sulphate transfer from 4-nitrophenylsulphate to the phenolic acceptor. High acceptor concentrations lead to inhibition of the reaction; very low concentrations give deviation from Michaelis-Menten kinetics. From the kinetic data, a mechanism is suggested in which an enzyme-adenosine 3'-phosphate 5'-phosphosulphate complex is formed in situ, with which the acceptor then interacts to give the final sulphate transfer. The system employed here is useful for the study of phenol sulphotransferase in view of the difficulty in obtaining adequate amounts of adenosine 3'-phosphate 5'-phosphosulphate from commercial sources.

The kinetics of the reversible sulphotransferase-catalysed reaction between p-nitrophenol and 3′-phosphoadenylyl sulphate to give p-nitrophenyl sulphate and adenosine 3′,5′-diphosphate have been investigated using a partially purified sulphotransferase from guinea-pig liver. From a study of the initial velocities of the reactions in the forward and reverse directions at different substrate concentrations, and of the inhibitory effects of the products on the forward reaction, it was concluded that the mechanism was that of a rapid equilibrium random bi bi reaction upon which was superimposed the formation of a dead-end complex of the enzyme, p-nitrophenol and adenosine 3′,5′-diphosphate. Studies of the specificity of the enzyme have been made. Attempts to detect a transfer reaction between p-nitrophenyl sulphate and 2-naphthol with adenosine 3′,5′-diphosphate as a cofactor were unsuccessful.