Kerem Teralı

The interactions of the classic phytohormones gibberellic acid (gibberellin A 3 , GA 3 ) and abscisic acid (dormin, ABA), which antagonistically regulate several developmental processes and stress responses in higher plants, with human placental glutathione S ‐transferase P1‐1 ( hp GSTP1‐1), an enzyme that plays a role in endo‐ or xenobiotic detoxification and regulation of cell survival and apoptosis, were investigated. The inhibitory potencies of ABA and GA 3 against hp GSTP1, as well as the types of inhibition and the kinetic parameters, were determined by making use of both enzyme kinetic graphs and SPSS nonlinear regression models. The structural basis for the interaction between hp GSTP1‐1 and phytohormones was predicted with the aid of molecular docking simulations. The IC 50 values of ABA and GA 3 were 5.3 and 5.0 mM, respectively. Both phytohormones inhibited hp GSTP1‐1 in competitive manner with respect to the cosubstrates GSH and CDNB. When ABA was the inhibitor at [CDNB] f –[GSH] v and at [GSH] f –[CDNB] v , V m , K m , and K i values were statistically estimated to be 205 ± 16 μmol/min‐mg protein, 1.32 ± 0.18 mM, 1.95 ± 0.25 mM and 175 ± 6 μmol/min‐mg protein, 0.85 ± 0.06 mM, 1.85 ± 0.16 mM, respectively. On the other hand, the kinetic parameters V m , K m , and K i obtained with GA 3 at [CDNB] f –[GSH] v and at [GSH] f –[CDNB] v were found to be 303 ± 14 μmol/min‐mg protein, 1.77 ± 0.13 mM, 3.38 ± 0.26 mM and 249 ± 7 μmol/min‐mg protein, 1.43 ± 0.07 mM, 2.89 ± 0.19 mM, respectively. Both phytohormones had the potential to engage in hydrogen‐bonding and electrostatic interactions with the key residues that line the G‐ and H‐sites of the enzyme's catalytic center. Inhibitory actions of ABA/GA 3 on hp GSTP1‐1 may guide medicinal chemists through the structure‐based design of novel antineoplastic agents. It should be noted, however, that the same interactions may also render fetuses vulnerable to the potentially toxic effects of xenobiotics and noxious endobiotics.

Background: Compromises in the cellular enzymatic defense barrier can increase the duration of exposure to electrophiles and the severity of toxicity they may incur. Objective: In this mini-review, we discuss the inhibition of the enzymatic defense systems by different antidepressants commonly prescribed worldwide as well as herbal products used for various forms of depression. Methods: Our work primarily focused on the interactions of two prominent biotransformation enzyme systems, namely glutathione S-transferases and cholinesterases, with tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and hypericin. Results: The antidepressants exert considerable inhibitory effects against glutathione S-transferases and butyrylcholinesterase. Conclusion: The outcomes of available published studies and their implications for health and disease are discussed here in detail.