Abstract
Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of catechol and phenolic drugs and xenobiotic compounds. Platelets and other tissues contain at least two forms of PST, forms that have been designated the “TL” and the “TS” forms. We measured the thermal stability of platelet TS PST in blood samples from 218 randomly selected unrelated subjects by heating platelet homogenates at 44° C for 15 min. Thermal stability was expressed as the ratio of the enzyme activity remaining after preincubation to that in an unheated sample, a heated/control (H/C) ratio. The frequency distribution of H/C ratios for this population sample was bimodal, with a nadir at an H/C ratio of 0.33. Of the 218 subjects studied, 29 (13.3%) had thermolabile TS PST (H/C<0.33). Platelet samples were then obtained from subjects with thermolabile and thermostable TS platelet PST. PST activity in these platelet samples had similar apparent Km constants for substrates. IC50 values for inhibition of TS PST by 2,6-dichloro-4-nitrophenol in these samples were also nearly identical. The results of experiments in which platelet homogenates from subjects with thermolabile and thermostable TS PST were mixed and the results of experiments in which platelet homogenates were subjected to gel filtration chromatography were compatible with the conclusion that individual differences in TS PST thermal stability were properties of PST itself. Finally, there was a significant familial aggregation of the trait of thermolabile TS PST when H/C ratios were measured in platelet homogenates from 231 members of 49 randomly selected families.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Anderson, R. J., and Jackson, B. L. (1984). Human platelet phenol sulfotransferase: Stability of two forms of the enzyme with time and presence of a racial difference. Clin. Chim. Acta 138185.
Anderson, R. J., and Weinshilboum, R. M. (1980). Phenolsulfotransferase in human tissue: Radiochemical enzymatic assay and biochemical properties. Clin. Chim. Acta 10379.
Anderson, R. J., Weinshilboum, R. M., Phillips, S. F., and Broughton, D. D. (1981). Human platelet phenol sulfotransferase: Assay procedure, substrate, and tissue correlations. Clin. Chim. Acta 110157.
Bonham-Carter, S. M., Glover, V., Sandler, M., Gillman, P. K., and Bridges, P. K. (1981). Human platelet phenolsulphotransferase: Separate control of the two forms and activity range in depressive illness. Clin. Chim. Acta 117333.
Bonham-Carter, S. M., Rein, G., Glover, V., Sandler, M., and Caldwell, J. (1983). Human platelet phenolsulphotransferase M and P: Substrate specificities and correlation with in vivo sulphoconjugation of paracetamol and salicylamide. Br. J. Clin. Pharmacol. 15323.
Campbell, N. R. C., and Weinshilboum, R. M. (1984). Human liver phenol sulfotransferase: Partial purification of the “TS” form. Fed. Proc. 43339.
Cleland, W. W. (1983). Computer programmes for processing enzyme kinetic data. Nature 198463.
Finney, D. F. (1971). Probit Analysis Cambridge University Press, Cambridge, England.
Foldes, A., and Meek, J. L. (1973). Rat brain phenolsulfotransferase—Partial purification and some properties. Biochim. Biophys. Acta 327365.
Hart, R. F., Renskers, K. J., Nelson, E. B., and Roth, J. A. (1979). Localization and characterization of phenol sulfotransferase in human platelets. Life Sci. 24125.
Keith, R. A., Van Loon, J., Wussow, L. F., and Weinshilboum, R. M. (1983). Thiol methylation pharmacogenetics: Heritability of human erythrocyte thiol methyltransferase activity. Clin. Pharmacol. Ther. 34521.
Langridge, J. (1968). Genetic and enzymatic experiments relating to the tertiary structure of β-galactosidase. J. Bacteriol. 961711.
Rein, G., Glover, V., and Sandler, M. (1981). Phenolsulphotransferase in human tissue: Evidence for multiple forms. In Sandler, M., and Usdin, E. (eds.), Phenolsulfotransferase in Mental Health Research Macmillan, London and Basingstoke, England, pp. 98–126.
Rein, G., Glover, V., and Sandler, M. (1982). Multiple forms of phenolsulphotransferase in human tissues: Selective inhibition by dichloronitrophenol. Biochem. Pharmacol. 311893.
Reiter, C., and Weinshilboum, R. M. (1982a). Acetaminophen and phenol: Substrates for both a thermostable and a thermolabile form of human platelet phenol sulphotransferase. J. Pharmacol. Exp. Ther. 22143.
Reiter, C., and Weinshilboum, R. (1982b). Platelet phenol sulfotransferase activity: Correlation with sulfate conjugation of acetaminophen. Clin. Pharmacol. Ther. 32612.
Reiter, C., Mwaluko, G., Dunnette, J., Van Loon, J., and Weinshilboum, R. (1983). Thermolabile and thermostable human platelet phenol sulfotransferase: Substrate specificity and physical separation. Naunyn-Schmied. Arch. Pharmacol. 324140.
Roy, A. B. (1981). Sulfotransferases. In Mulder, G. J. (ed.), Sulfation of Drugs and Related Compounds CRC Press, Boca Raton, Fla., pp. 83–130.
Sokal, R. R., and Rohlf, R. J. (1981). Biometry: The Principles and Practice of Statistics in Biological Research W. H. Freeman, San Francisco.
Weinshilboum, R. M. (1981). Enzyme thermal stability and population genetic studies: Application to erythrocyte catechol-0-methyltransferase and plasma dopamine-β-hydroxylase. In Gershon, E. S., Matthysse, S., Breakefield, X. O., and Ciaranello, C. D. (eds.), Genetic Strategies in Psychobiology and Psychiatry Boxwood Press, Pacific Grove, Calif. pp. 79–94.
Wilkinson, G. N. (1961). Statistical estimations in enzyme kinetics. Biochem. J. 80324.
Young, W. F., Jr., Laws, E. R., Jr., Sharbrough, F. W., and Weinshilboum, R. M. (1984). Phenol sulfotransferase: Correlation of brain and platelet activities in twelve patients. Clin. Res. 32:481A.
Author information
Authors and Affiliations
Additional information
This work was supported in part by NIH Grant GM 28157. Dr. Weinshilboum is a Burroughs Wellcome Scholar in Clinical Pharmacology.
Rights and permissions
About this article
Cite this article
Van Loon, J., Weinshilboum, R.M. Human platelet phenol sulfotransferase: Familial variation in thermal stability of the TS form. Biochem Genet 22, 997–1014 (1984). https://doi.org/10.1007/BF00499627
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00499627