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

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 ( = 194) by liquid chromatography-t...

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Bibliographic Details
Published in:Drug metabolism and disposition 2019-08, Vol.47 (8), p.818-831
Main Authors: Ladumor, Mayur K, Bhatt, Deepak Kumar, Gaedigk, Andrea, Sharma, Sheena, Thakur, Aarzoo, Pearce, Robin E, Leeder, J Steven, Bolger, Michael B, Singh, Saranjit, Prasad, Bhagwat
Format: Article
Language:English
Subjects:
Acetaminophen
Acetaminophen - pharmacokinetics
Adolescent
Adolescents
Adult
Age
Age Factors
Aged
Analgesics
Area Under Curve
Biological Variation, Population - physiology
Child
Child, Preschool
Children
Chromatography, High Pressure Liquid
Cytochrome
Cytochrome P450
Cytochromes P450
Cytosol
Cytosol - metabolism
Drug Interactions - physiology
Enzymes
Ethnicity
Female
Humans
Infant
Infant, Newborn
Isoforms
Liquid chromatography
Liver
Liver - cytology
Liver - metabolism
Male
Mass spectrometry
Mass spectroscopy
Metabolism
Middle Aged
Minority & ethnic groups
Models, Biological
Neonates
Ontogeny
Protein turnover
Proteins
Proteomics
Regression analysis
Sex Factors
Sulfates - metabolism
Sulfation
Sulfotransferases - analysis
Sulfotransferases - metabolism
Tandem Mass Spectrometry
Young Adult
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Summary: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 ( = 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
ISSN:0090-9556
1521-009X
1521-009X
DOI:10.1124/dmd.119.086462