Advisory Committee Chair
Charles N Falany
Advisory Committee Members
Karina J Yoon
Michelle V Fanucchi
Peter E Prevelige
Stephen Barnes
Document Type
Dissertation
Date of Award
2017
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Human cytosolic sulfotransferase 1C4 (hSULT1C4) is a dimeric Phase II drug-metabolizing enzyme primarily expressed in the developing fetus. SULTs facilitate the transfer of a hydrophilic sulfonate moiety from 3’-phosphoadenosine-5’-phosphosulfate (PAPS) onto an acceptor substrate altering the substrate’s biological activity and increasing the compound’s water solubility. While several of the hSULTs’ endogenous and xenobiotic substrates have been identified, the physiological function of hSULT1C4 remains unknown. The fetal expression of hSULT1C4 leads to the hypothesis that the function of this enzyme may be to regulate metabolic and hormonal signaling molecules, such as estrogenic compounds, that may be generated or consumed by the mother during fetal development. Human SULT1C4 has previously been shown to sulfonate estrogenic compounds, such as catechol estrogens; therefore, this study focused on the expression and purification of hSULT1C4 in order to further characterize the ability of this enzyme to sulfonate estrogenic compounds. Molecular modeling of the native properties of hSULT1C4 helped to establish a novel purification protocol for hSULT1C4. The optimal activity assay conditions for hSULT1C4 were determined to be pH 7.4 at 37°C for up to 10 minutes. Kinetic analysis revealed the enzyme’s reduced affinity for PAPS compared to 3′, 5′-diphosphoadenosine (PAP). Human SULT1C4 sulfonated all the estrogenic compounds tested, including dietary flavonoids and environmental estrogens; however, the enzyme has a higher affinity for sulfonation of flavonoids. These results suggest hSULT1C4 could be metabolizing and regulating hormone signaling pathways during human fetal development.
Recommended Citation
Guidry, Amber Lynn, "Purification, Characterization, And Enzymatic Activity Of Human Cytosolic Sulfotransferase 1C4" (2017). All ETDs from UAB. 1805.
https://digitalcommons.library.uab.edu/etd-collection/1805