XXXX sulfotransferase 1A1 activity in @entity1 liver: kinetic properties, interindividual variation and re-evaluation of the suitability of @entity11921 as a probe substrate.

@entity1 @entity4913 @entity70552 @entity3971 @entity11921
Sulfation is an important metabolic pathway in @entity1 for xenobiotics, hormones and neurotransmitters, and is catalysed by the cytosolic sulfotransferase (SULT) enzymes. @entity3971 SULTs, especially @entity4913 , are particularly important in xenobiotic and drug metabolism because of their broad substrate specificity and extensive tissue distribution. A common variant @entity4913 allozyme ( @entity4913 *2) exists in the population, and is less stable than the wild-type @entity4913 *1. @entity11921 is widely used as a substrate for quantifying @entity4913 activity. However, our kinetic experiments suggest that @entity11921 is not an ideal substrate when determining @entity4913 activity in @entity1 liver. Assays with a bank of 68 @entity1 liver cytosols revealed three distinct kinetic profiles for @entity11921 sulfation in the population: linear, biphasic and inhibition. Sulfation of @entity11921 by purified, recombinant @entity4913 *1 and @entity4913 *2 shows marked substrate inhibition, with inhibition at @entity11921 concentrations greater than 4 and 10 microM, respectively. Furthermore, sulfation of @entity11921 by purified recombinant @entity70552 was significant at concentrations of @entity11921 less than 10 microM. Western blots showed that the @entity4913 levels in liver are highly variable between liver samples and that no correlation was observed between @entity4913 activity and protein level in liver cytosols. However, a correlation between @entity4913 activity and protein level was observed in @entity1 placental cytosols, where @entity70552 is not expressed. We believe that in @entity1 liver other SULT isoforms (particularly @entity70552 ) contribute to the sulfation of @entity11921 . Therefore, @entity11921 is not an ideal substrate with which to quantitate @entity4913 activity in @entity1 liver tissue.
