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Ontogeny of Hepatic Sulfotransferases and Prediction of Age-Dependent Fractional Contribution of Sulfation in Acetaminophen Metabolism

Authors :
J. Steven Leeder
Deepak Kumar Bhatt
Mayur K. Ladumor
Andrea Gaedigk
Robin E. Pearce
Michael B. Bolger
Aarzoo Thakur
Saranjit Singh
Bhagwat Prasad
Sheena Sharma
Source :
Drug Metab Dispos
Publication Year :
2019
Publisher :
American Society for Pharmacology & Experimental Therapeutics (ASPET), 2019.

Abstract

Cytosolic sulfotransferases (SULTs), including SULT1A, SULT1B, SULT1E, and SULT2A isoforms, play noteworthy roles in xenobiotic and endobiotic metabolism. We quantified the protein abundances of SULT1A1, SULT1A3, SULT1B1, and SULT2A1 in human liver cytosol samples (n = 194) by liquid chromatography–tandem mass spectrometry proteomics. The data were analyzed for their associations by age, sex, genotype, and ethnicity of the donors. SULT1A1, SULT1B1, and SULT2A1 showed significant age-dependent protein abundance, whereas SULT1A3 was invariable across 0–70 years. The respective mean abundances of SULT1A1, SULT1B1, and SULT2A1 in neonatal samples was 24%, 19%, and 38% of the adult levels. Interestingly, unlike UDP-glucuronosyltransferases and cytochrome P450 enzymes, SULT1A1 and SULT2A1 showed the highest abundance during early childhood (1 to

Details

ISSN :
1521009X and 00909556
Volume :
47
Database :
OpenAIRE
Journal :
Drug Metabolism and Disposition
Accession number :
edsair.doi.dedup.....e2491450e204b7d223d0abebb4496632
Full Text :
https://doi.org/10.1124/dmd.119.086462