Version 1
: Received: 22 May 2024 / Approved: 5 June 2024 / Online: 5 June 2024 (13:36:40 CEST)
How to cite:
Alatwi, E.; Bairam, A. Impact of Genetic Polymorphisms on the Sulfation of Dehydroepiandrosterone and 17-β Estradiol by Human Cytosolic Sulfotransferase SULT2B1a. Preprints2024, 2024060268. https://doi.org/10.20944/preprints202406.0268.v1
Alatwi, E.; Bairam, A. Impact of Genetic Polymorphisms on the Sulfation of Dehydroepiandrosterone and 17-β Estradiol by Human Cytosolic Sulfotransferase SULT2B1a. Preprints 2024, 2024060268. https://doi.org/10.20944/preprints202406.0268.v1
Alatwi, E.; Bairam, A. Impact of Genetic Polymorphisms on the Sulfation of Dehydroepiandrosterone and 17-β Estradiol by Human Cytosolic Sulfotransferase SULT2B1a. Preprints2024, 2024060268. https://doi.org/10.20944/preprints202406.0268.v1
APA Style
Alatwi, E., & Bairam, A. (2024). Impact of Genetic Polymorphisms on the Sulfation of Dehydroepiandrosterone and 17-β Estradiol by Human Cytosolic Sulfotransferase SULT2B1a. Preprints. https://doi.org/10.20944/preprints202406.0268.v1
Chicago/Turabian Style
Alatwi, E. and Ahsan Bairam. 2024 "Impact of Genetic Polymorphisms on the Sulfation of Dehydroepiandrosterone and 17-β Estradiol by Human Cytosolic Sulfotransferase SULT2B1a" Preprints. https://doi.org/10.20944/preprints202406.0268.v1
Abstract
Dehydroepiandrosterone (DHEA) is considered an endogenous steroid hormone precursor, and 17-ß Estradiol (E2) is one of the estrogen steroid hormones. Of the thirteen known human cytosolic sulfotransferases (SULTs), SULT2B1a has been shown to be expressed in steroid hormone-responsive tissues such as the prostate, ovary, and placenta, as well as the fetal brain. Previous studies have demonstrated that SULT2B1a is capable of sulfating 3β-hydroxysteroids such as DHEA and pregnenolone. The present study aimed to investigate the effects of human SULT2B1 SNPs on the enzymatic characteristics of SULT2B1a allozymes in mediating the sulfation of DHEA and E2. To inspect the effects of single nucleotide polymorphisms of the SULT2B1 gene on the sulfation of DHEA and E2 by SULT2B1a allozymes, 13 recombinant SULT2B1a allozymes were produced, expressed, and purified using established procedures. 13 SULT 2B1a nonsynonymous missense coding SNPs (cSNPs) were selected among numerous identified human SULT 2B1a SNPs by a comprehensive database search. The corresponding cDNAs, packaged in pGEX-2TK expression vector, and encoding the selected 13 SULT2B1a allozymes, have been generated by performing site-directed mutagenesis. These were then bacterially expressed in BL21 E. coli cells and purified using glutathione-Sepharose affinity chromatography. The purified allozymes were tested for their ability to sulfonate DHEA and E2. In terms of the kinetic parameters, the wild-type SULT2B1a exhibited higher enzyme affinity towards DHEA than with E2. In comparison with the wild-type SULT2B1a, the purified allozymes displayed differential sulfating activities towards DHEA and E2. Accordingly, these findings indicate an apparent effect of SULT2B1 cSNPs on the sulfating activities of SULT2B1a allozymes toward DHEA and E2, and may provide for a better understanding of the pharmacokinetics of DHEA and E2 in individuals with differing SULT2B1a genotypes.
Keywords
DHEA; E2; sulfation; SULT2B1a; SNPs
Subject
Medicine and Pharmacology, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
