TY - JOUR
T1 - Human 3′-phosphoadenosine 5′-phosphosulfate synthetase (PAPS-S) pharmaco-genetics
T2 - Gene cloning and chromosomal localization
AU - Otterness, P. M.
AU - Mitchell, S.
AU - Moon, E.
AU - Kim, U. J.
AU - Weinshilboum, R. M.
PY - 1999
Y1 - 1999
N2 - 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.
AB - 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.
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U2 - 10.1016/S0009-9236(99)80231-8
DO - 10.1016/S0009-9236(99)80231-8
M3 - Article
AN - SCOPUS:33749107579
SN - 0009-9236
VL - 65
SP - 175
JO - Clinical pharmacology and therapeutics
JF - Clinical pharmacology and therapeutics
IS - 2
ER -