Sulfation of acetaminophen in isolated rat hepatocytes. Relationship to sulfate ion concentrations and intracellular levels of 3'-phosphoadenosine-5'-phosphosulfate.
The relationships among sulfate ion concentration, rates of acetaminophen (APAP) sulfation, and intracellular levels of the cofactor for sulfation, 3'-phosphoadenosine-5'-phosphosulfate (PAPS) were examined in isolated rat hepatocytes. APAP sulfation rates increased as the sulfate ion concentration was raised to 1.0 mM, after which further increases in sulfate ion concentration failed to influence rates of sulfation. Cellular PAPS levels were directly related to the sulfate ion concentration both in the presence and absence of APAP. However, PAPS levels were reduced by as much as 93% in the presence of APAP. At sulfate ion concentrations below 1.0 mM, the dependence of both rates of sulfation and levels of PAPS on the availability of sulfate ion indicates that rates of sulfation may be limited by the availability of PAPS when sulfate ion concentrations are in the physiological range. Because higher sulfate ion concentrations (greater than 1.0 mM) increased intracellular concentrations of PAPS without producing corresponding increases in APAP sulfation, phenol sulfotransferase activity may be rate limiting in the presence of high concentrations of sulfate ion.
Sweeny
D J
DJ
Department of Pharmacology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Reinke
L A
LA
D000082:Acetaminophen / Q000378:metabolism*; D000227:Adenine Nucleotides / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013431:Sulfates / Q000378:metabolism*
D000227:Adenine Nucleotides; D013431:Sulfates; D000082:Acetaminophen; D010724:Phosphoadenosine Phosphosulfate