Human 3′-phosphoadenosine 5′-phosphosulfate synthetase (PAPS-S) pharmaco-genetics: Gene cloning and chromosomal localization

Sulfation is an important pathway in the metabolism of many drugs, other xenobiotics, neurotransmitters and hormones. Sulfate conjugation is catalyzed by cytosolic sulfotransferase enzymes which require PAPS. Sulfation can be regulated by PAPS availability. For example, PAPS levels can be controlled, in part, by inorganic sulfate concentrations. We set out to determine whether genetic variation in the activity or properties of PAPS-S might be another factor regulating individual differences in sulfate conjugation. The human PAPS-S cDNA has recently been cloned. We have now cloned and characterized the gene for human PAPS-S. This gene contained 12 exons and mapped to human chromosome 4q21.2-4q24 by PCR. We identified 8 potential PAPS-S single nucleotide polymorphisms (SNPs), 4 of which altered encoded amino acid. Identification of SNPs within the PAPS-S gene will enable us to determine whether these polymorphisms might be responsible for individual variations in PAPS levels and, therefore, might contribute to variation in sulfation in humans.