Variable Sulfation of Dietary Polyphenols by Recombinant Human Sulfotransferase (SULT) 1A1 Genetic Variants and SULT1E1

@article{Ung2007VariableSO,
  title={Variable Sulfation of Dietary Polyphenols by Recombinant Human Sulfotransferase (SULT) 1A1 Genetic Variants and SULT1E1},
  author={Din Ung and Swati Nagar},
  journal={Drug Metabolism and Disposition},
  year={2007},
  volume={35},
  pages={740 - 746}
}
  • D. UngS. Nagar
  • Published 1 May 2007
  • Biology
  • Drug Metabolism and Disposition
Human cytosolic sulfotransferases (SULTs) catalyze the sulfate conjugation of several important endo- and xenobiotics. Among the superfamily of SULT enzymes, SULT1A1 catalyzes the sulfation of small planar phenolic compounds, whereas SULT1E1 has a major role in estrogen conjugation. The human SULT1A1 gene has common single nucleotide polymorphisms that define three allozymes, SULT1A1*1, *2, and *3. The enzyme kinetics of SULT1A1 allozymes and SULT1E1 were characterized for the polyphenolic… 

Figures and Tables from this paper

Expression, purification and characterization of human cytosolic sulfotransferase (SULT) 1C4

Human SULT1C4 sulfonated all the estrogenic compounds tested, including dietary flavonoids and environmental estrogens; however, the enzyme has a higher affinity for sulfonation of flavonoid.

Specific estrogen sulfotransferase (SULT1E1) substrates and molecular imaging probe candidates

In vivo assays of SULT1E1 functional activity are now feasible in humans, as in vitro sulfation assays showed alkyl and aryl substitutions to a fused heterocyclic system modeled after β-naphthol, based on compounds that interact with the estrogen receptor.

In vitro and in vivo conjugation of dietary hydroxycinnamic acids by UDP-glucuronosyltransferases and sulfotransferases in humans.

Regioselective sulfation and glucuronidation of phenolics: insights into the structural basis.

It is concluded that the regioselective nature of these phase II enzymes is determined by the size and shape of the binding pocket, which is of great importance in predicting contribution of sulfation/ glucuronidation to drug and metabolite disposition in vivo.

Trans-resveratrol-mediated inhibition of β-oestradiol conjugation in MCF-7 cells stably expressing human sulfotransferases SULT1A1 or SULT1E1, and human liver microsomes

The results corroborate the reported significant inhibition of SULT1E1-mediated E2 sulfation in vitro by resveratrol and suggest that resver atrol may interact with E2 in vivo by inhibiting its conjugation.

Phase II Metabolism of Hesperetin by Individual UDP-Glucuronosyltransferases and Sulfotransferases and Rat and Human Tissue Samples

Results demonstrate that hesperetin is conjugated at positions 7 and 3′ and that major enzyme-specific differences in kinetics and regioselectivity for the UGT and SULT catalyzed conjugations exist, and help to explain discrepancies in metabolite patterns determined in tissues or systems with different expression of UGTs and Sults.

Identification and characterization of sulfonyltransferases catalyzing ethyl sulfate formation and their inhibition by polyphenols

Results revealed multiple SULT isoforms being capable of catalyzing the transfer of a sulfo group to ethanol; nevertheless, the relevance of SULTs’ polymorphism on the sulfonation of ethanol needs further appraisal.

Phase II metabolism of hesperetin by individual UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) and rat and human tissue samples

It is demonstrated that hesperetin is conjugated at positions 7 and 3’, and that major enzyme-specific differences in kinetics and regioselectivity for the UGT and SULT catalyzed conjugations exist, to explain discrepancies in metabolite patterns determined in tissues or systems with different expression of UGTs and Sults.

Estrogen Sulfotransferase (SULT1E1): Its Molecular Regulation, Polymorphisms, and Clinical Perspectives

This study gathered and reviewed various literature studies to outline several aspects of the function, molecular regulation, and polymorphisms of SULT1E1.
...

References

SHOWING 1-10 OF 43 REFERENCES

Sulfotransferase (SULT) 1A1 Polymorphic Variants *1, *2, and *3 Are Associated with Altered Enzymatic Activity, Cellular Phenotype, and Protein Degradation

Significant differences in activity of polymorphic SULT1A1 variants, including SULT 1A1*3, toward a variety of substrates are suggested, potentially critical for understanding interindividual variability in drug response and toxicity, as well as cancer risk and incidence.

Biochemical characterization and tissue distribution of human SULT2B1.

The catalytic activity toward dehydroepiandrosterone and dihydrotestosterone, biologically important androgens, coupled with expression in prostate suggests that SULT2B1 may play a novel regulatory role that protects against the mitogenic effects of androgens.

Phenol sulfotransferase pharmacogenetics in humans: association of common SULT1A1 alleles with TS PST phenotype.

Common SULT1A1 nucleotide polymorphisms that are associated with phenotypic variation in both platelet TS PST activity and thermal stability are reported, step toward understanding molecular mechanisms responsible for the genetic regulation of PSTs in humans.

Human sulfotransferases and their role in chemical metabolism.

Interindividual variation in sulfonation capacity may be important in determining an individual's response to xenobiotics, and recent studies have begun to suggest roles for SULT polymorphism in disease susceptibility.

Human estrogen sulfotransferase (SULT1E1) pharmacogenomics: gene resequencing and functional genomics

It is raised the possibility that genetically determined variation in SULT1E1‐catalyzed estrogen sulfation might contribute to the pathophysiology of estrogen‐dependent diseases as well as variation in the biotransformation of exogenously administered estrogens.

Phenol sulphotransferase SULT1A1*1 genotype is associated with reduced risk of colorectal cancer.

It is suggested that the high activity SULT1A1*1 allozyme protects against dietary and/or environmental chemicals involved in the pathogenesis of colorectal cancer.

Sulfation of resveratrol in human liver: Evidence of a major role for the sulfotransferases SULT1A1 and SULT1E1

The results elucidate the enzymatic pathways of resveratrol in human liver, which must be considered in humans following oral uptake of dietary resverate, and demonstrate that M1 is almost exclusively catalysed by SULT1A1 and only to a minor extent by Sult 1A2, 1A3 and 1E1, whereas M2 is selectively formed by SULTS1A2.

Sulfation through the looking glass—recent advances in sulfotransferase research for the curious

  • M. Coughtrie
  • Biology, Chemistry
    The Pharmacogenomics Journal
  • 2002
Improved understanding of these enzymes will have significant benefits in such diverse areas as drug design and development, cancer susceptibility, reproduction and development.