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Ahsan Bairam Dissertation.pdf (3.87 MB)

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Functional Genomic Studies On The Genetic Polymorphisms Of The Human Cytosolic Sulfotransferase 1A3 (SULT1A3)

Bairam, Ahsan F. Hasan
http://rave.ohiolink.edu/etdc/view?acc_num=mco1525192576343535

Abstract Details

2018, Doctor of Philosophy (PhD), University of Toledo, Experimental Therapeutics.
Previous studies have demonstrated the involvement of sulfoconjugation in the metabolism of catecholamines and serotonin (5-HT), as well as a wide range of xenobiotics including drugs. The study presented in this dissertation aimed to clarify the effects of coding single nucleotide polymorphisms (cSNPs) of the human SULT1A3 and SULT1A4 genes on the enzymatic characteristics of the sulfation of catecholamines, 5-HT, and selected drugs by SULT1A3 allozymes. Following a comprehensive search of different SULT1A3 and SULT1A4 genotypes, thirteen non-synonymous (missense) cSNPs of SULT1A3/SULT1A4 were identified. cDNAs encoding the corresponding SULT1A3 allozymes, packaged in pGEX-2T vector were generated by site-directed mutagenesis. Recombinant SULT1A3 allozymes were bacterially expressed and affinity-purified. Purified SULT1A3 allozymes were found to exhibit differential sulfating activities toward dopamine (DA), epinephrine (EP), norepinephrine (NE), 5-HT, acetaminophen (APAP), morphine, tapentadol, O-desmethyl tramadol (O-DMT), phenylephrine, and salbutamol, in comparison to the wild-type enzyme. Kinetic analyses further demonstrated differences in substrate affinity (as reflected by Km) and catalytic ativity (as reflected by Vmax) of different SULT1A3 allozymes. Collectively, the findings made provided useful information relevant to the differential metabolism of above-mentioned endogenous and xenobiotic compounds. Such information may eventually shed light on the correlation of particular SULT1A3/SULT1A4 genotypes to neuropathological disorders associated with abnormal levels of the monoamines that act as substrates for SULT1A3. Furthermore, these results obtained may in the future aid in designing personalized regimens of relevant drugs in order to optimize their efficacy and mitigate their adverse effects for individuals with distinct SULT1A3/SULT1A4 genotypes.
Ming-Cheh Liu (Committee Chair)
Ezdihar Hassoun (Committee Member)
Zahoor Shah (Committee Member)
Caren Steinmiller (Committee Member)
180 p.
Genetics; Pharmacology

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Citations

  • Bairam, A. F. H. (2018). Functional Genomic Studies On The Genetic Polymorphisms Of The Human Cytosolic Sulfotransferase 1A3 (SULT1A3) [Doctoral dissertation, University of Toledo]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=mco1525192576343535

    APA Style (7th edition)

  • Bairam, Ahsan. Functional Genomic Studies On The Genetic Polymorphisms Of The Human Cytosolic Sulfotransferase 1A3 (SULT1A3). 2018. University of Toledo, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=mco1525192576343535.

    MLA Style (8th edition)

  • Bairam, Ahsan. "Functional Genomic Studies On The Genetic Polymorphisms Of The Human Cytosolic Sulfotransferase 1A3 (SULT1A3)." Doctoral dissertation, University of Toledo, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=mco1525192576343535

    Chicago Manual of Style (17th edition)

mco1525192576343535
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This open access ETD is published by University of Toledo Health Science Campus and OhioLINK.