Human cytosolic sulfotransferase SULT1A1

Hempel, Nadine; Gamage, Niranjali; Martin, Jennifer L.; McManus, Michael E.

doi:10.1016/j.biocel.2006.10.002

Cited by 59 publications

(49 citation statements)

References 18 publications

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“…Figure 3 displays SULT expression "pies" of the most important human cytosolic transferases in human tissues. SULT1A1 is predominantly expressed in the liver (Hempel et al, 2007). In contrast to SULT1A1, the SULT1A3 enzyme was not detected in human adult liver.…”

Section: Human Forms Of Cytosolic Sults and Tissue Distributionmentioning

confidence: 82%

Phase II Drug Metabolism

Jančová¹,

Siller²

2012

Topics on Drug Metabolism

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Section: Human Forms Of Cytosolic Sults and Tissue Distributionmentioning

confidence: 82%

Phase II Drug Metabolism

Jančová¹,

Siller²

2012

Topics on Drug Metabolism

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“…Among several other important functions, sulfonation is also known to have a role in modulating the action of hormones and neurotransmitters and appears to be especially important during early human development (21,25,26,(47)(48)(49)(50)(51). There are various human sulfotransferases (both cytosolic and membrane-bound), but human cytosolic sulfotransferase SULT1A1, which acts on acetaminophen, has a broad substrate range and is one of the most important sulfotransferases for xenobiotic sulfonation as well as acting on several endogenous substrates (26,51). Additionally, a key feature of sulfonation in higher organisms is that all such reactions use PAPS as the universal sulfonate donor.…”

Section: Resultsmentioning

confidence: 99%

Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism

Clayton

Baker

Lindon

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

697

573

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We provide a demonstration in humans of the principle of pharmacometabonomics by showing a clear connection between an individual's metabolic phenotype, in the form of a predose urinary metabolite profile, and the metabolic fate of a standard dose of the widely used analgesic acetaminophen. Predose and postdose urinary metabolite profiles were determined by 1 H NMR spectroscopy. The predose spectra were statistically analyzed in relation to drug metabolite excretion to detect predose biomarkers of drug fate and a human-gut microbiome cometabolite predictor was identified. Thus, we found that individuals having high predose urinary levels of p-cresol sulfate had low postdose urinary ratios of acetaminophen sulfate to acetaminophen glucuronide. We conclude that, in individuals with high bacterially mediated p-cresol generation, competitive O-sulfonation of p-cresol reduces the effective systemic capacity to sulfonate acetaminophen. Given that acetaminophen is such a widely used and seemingly well-understood drug, this finding provides a clear demonstration of the immense potential and power of the pharmacometabonomic approach. However, we expect many other sulfonation reactions to be similarly affected by competition with p-cresol and our finding also has important implications for certain diseases as well as for the variable responses induced by many different drugs and xenobiotics. We propose that assessing the effects of microbiome activity should be an integral part of pharmaceutical development and of personalized health care. Furthermore, we envisage that gut bacterial populations might be deliberately manipulated to improve drug efficacy and to reduce adverse drug reactions.T he effects of drug treatments can vary greatly between different individuals, and pharmacogenomics has been widely advocated as a potential means of personalizing human drug treatments to increase drug efficacy and to decrease adverse reactions (1-6). However, environmental factors (such as nutritional status, gut bacterial activities, age, disease, and other drug use) are also important determinants of individual metabolic phenotypes, which modulate drug metabolism, efficacy, and toxicity. Such environmental complications, which may also alter gene expression, will tend to limit the usefulness of predictions of drug-induced responses that are based only on genomic differences (7,8). For instance, for many classes of compound, enzyme induction state, which is environmentally determined, influences drug metabolism and toxicity and this is not captured in genomic data. Recognizing this important limitation of pharmacogenomics, a different approach to personalized drug treatment has recently been proposed wherein predose metabolite profiling would instead be used to predict a subject's responses to potential drug interventions (9). This ''pharmacometabonomic'' approach has a number of major advantages, which include the ready availability and relative ease of analysis of biofluids, such as urine and blood plasma, as well as the fact that ...

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“…Sulfotransferases (SULTs) are one of the major superfamily of phase II drug metabolizing enzymes (Bojarova and Williams, 2008;Chapman et al, 2004;Gamage et al, 2006;Hempel et al, 2007;Kauffman, 2004;Rath et al, 2004;Runge-Morris and Kocarek, 2005;Wang and James, 2006). They catalyze the sulfation of hydroxyl-containing compounds.…”

Section: Introductionmentioning

confidence: 99%

“…Sulfation of xenobiotics is mainly associated with detoxification: biotransformation of a relatively hydrophobic xenobiotic into a more water-soluble sulfuric ester that is readily excreted. However, there are numerous important exceptions wherein the formation of chemically reactive sulfuric esters is an essential step in the metabolic pathways leading to carcinogenic responses (Hempel et al, 2007;Gallucci and Mickle, 2006).…”

Section: Introductionmentioning

confidence: 99%

Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

Zhou¹

2010

American Journal of Pharmacology and Toxicology

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Problem statement: Sulfotransferases (SULTs) are important phase II drug metabolizing enzymes. They also regulate the biological activities of various hormones. To the best of our knowledge, psychostimulants regulation of SULTs is basically not studied except one article reported that Methamphetamine (METH) treatment induced rat amygdale rSULT1A1 mRNA 4.3 fold by using microarray method to identify a series of candidate genes after single-dose METH treatment. The psychostimulant METH is used to treat disorders such as attention deficit, narcolepsy and obesity. It is also a highly addictive drug that causes serious social problems. The abuse of this drug leads to the damage of monoaminergic systems in the mammalian brain. It is important to understand how SULT expressions are regulated by psychostimulants. Approach: This study was performed to evaluate the effect of METH on SULT gene expressions in rat liver and brain. METH (0, 1, 5, 20 mg kg −1 day −1 ) was used to treat male and female rats for 7 days by oral administration. Rat livers and brains were collected 24 h after the final drug treatment. Western blot and real-time RT-PCR were used to investigate the effect of METH on SULT protein and mRNA expression, respectively, in rat liver and brain. Results: Proteins and mRNAs of rSULT1A1, rSULT2A1 and rSULT1E1 were induced in liver and brain of both male and female rats following METH treatment. rSULT1E1 was induced at much higher level compared to that of rSULT1A1 and rSULT2A1. Brain inductions were found to be much higher than those found in liver. Conclusion: These data suggest an important role of the central dopaminergic system in the regulation of liver and brain rSULT expressions.

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Human cytosolic sulfotransferase SULT1A1

Cited by 59 publications

References 18 publications

Phase II Drug Metabolism

Phase II Drug Metabolism

Pharmacometabonomic identification of a significant host-microbiome metabolic interaction affecting human drug metabolism

Methamphetamine Regulation of Sulfotransferases in Rat Liver and Brain

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