Sulfation pharmacogenetics: correlation of human platelet and small intestinal phenol sulfotransferase.
Phenol sulfotransferase (PST) catalyzes the sulfate conjugation of phenolic drugs. All human tissues studied contain a thermostable (TS) form of PST, which catalyzes the sulfate conjugation of "simple" phenols such as p-nitrophenol, and a thermolabile (TL) form, which catalyzes the sulfation of dopamine and other monoamines. In the present study we tested the hypothesis that genetically controlled levels of TS and TL PST activity in the platelet, as well as inherited variations in the thermal stability of platelet TS PST, might reflect those same characteristics of the enzyme in the less accessible tissue, human small intestinal mucosa. Platelet TS and TL PST activities and TS PST thermal stability were measured in blood samples from 45 randomly selected healthy subjects, and 14 of those subjects were selected to have intestinal biopsies performed. There was a significant correlation between levels of platelet and jejunal mucosal TS PST activity (rs = 0.574, p less than 0.030), but there was not a significant correlation between levels of TL PST activity in the two tissues (rs = 0.265, p = 0.368). There was also a significant correlation between the trait of TS PST thermal stability in the two tissues (rs = 0.828, p less than 0.0001). These observations suggest that inherited variations in TS PST activity and thermal stability in an easily obtained tissue, the platelet, might be used to predict individual differences of those properties of the enzyme in the human small intestine, an organ that plays an important role in drug metabolism.
Sundaram
R S
RS
Department of Pharmacology, Mayo Clinic, Rochester, MN 55905.
Van Loon
J A
JA
Tucker
R
R
Weinshilboum
R M
RM
D000328:Adult; D015239:Arylsulfotransferase / Q000235:genetics / Q000378:metabolism*; D001792:Blood Platelets / Q000201:enzymology*; D004795:Enzyme Stability; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology*; D007583:Jejunum / Q000201:enzymology*; D008297:Male; D008875:Middle Aged
D015239:Arylsulfotransferase