Nutritionally and chemically induced impairment of sulfate activation and sulfation of xenobiotics in vivo.
Sulfation requires 3'-phosphoadenosine 5'-phosphosulfate (PAPS) as the sulfate donor. In the search for methods to inhibit sulfation reactions via impairment of PAPS synthesis, two experimental conditions have been tested in rats. A low-sulfur diet, which does not deplete hepatic glutathione, reduced inorganic sulfate but not PAPS levels in the liver and moderately decreased sulfation of acetaminophen. Administration of molybdate, which is an alternative substrate for intestinal and renal sulfate transport as well as for ATP-sulfurylase, depleted both sulfate and PAPS in liver and markedly inhibited sulfation of acetaminophen. Therefore, administration of molybdate may be used as an experimental tool to study the role of sulfation in the fate and effect of xenobiotics.
Gregus
Z
Z
Department of Pharmacology, University Medical School of Pécs, Hungary.
Oguro
T
T
Klaassen
C D
CD
D000082:Acetaminophen / Q000378:metabolism* / Q000652:urine; D000818:Animals; D001646:Bile / Q000378:metabolism; D004032:Diet; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008982:Molybdenum / Q000008:administration & dosage / Q000494:pharmacology*; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism*; D051381:Rats; D013430:Sulfate Adenylyltransferase / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism*; D013455:Sulfur / Q000008:administration & dosage; D015262:Xenobiotics / Q000378:metabolism*
D013431:Sulfates; D015262:Xenobiotics; C044659:molybdate; D000082:Acetaminophen; D010724:Phosphoadenosine Phosphosulfate; D013455:Sulfur; D008982:Molybdenum; D013430:Sulfate Adenylyltransferase; D005978:Glutathione