In vitro Trials to counteract the inhibitory effect of β-oestradiol and ethynyloestradiol on the B6-dependent kynurenine aminotransferase enzyme

El-Zoghby, S.M.; El‐Sewedy, S.M.; Saad, Abeer A.; Mostafa, M. A.; Ebied, Samia; Abdel-Tawab, G.A.

doi:10.1016/0006-2952(76)90040-x

Cited by 4 publications

(3 citation statements)

References 11 publications

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“…Trp research has been actively practiced in Egypt from the 1960s on, mainly in relation to Schistosoma infestation, by the group of Dr Gamal Abdel-Tawab at the National Research Centre in Gizeh and the Medical Research Institute in Alexandria (see, e.g., [1–4]). Trp research is a fruitful area that never disappoints.…”

Section: Introductionmentioning

confidence: 99%

Tryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention

Badawy

2019

Egyptian Journal of Basic and Clinical Pharmacology

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The essential amino acid L -tryptophan (Trp) undergoes extensive metabolism along several pathways, resulting in production of many biologically active metabolites which exert profound effects on physiological processes. The disturbance in Trp metabolism and disposition in many disease states provides a basis for exploring multiple targets for pharmaco-therapeutic interventions. In particular, the kynurenine pathway of Trp degradation is currently at the forefront of immunological research and immunotherapy. In this review, I shall consider mammalian Trp metabolism in health and disease and outline the intervention targets. It is hoped that this account will provide a stimulus for pharmacologists and others to conduct further studies in this rich area of biomedical research and therapeutics.

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Section: Introductionmentioning

confidence: 99%

Tryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention

Badawy

2019

Egyptian Journal of Basic and Clinical Pharmacology

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“…9 The effects of E2 or ethinyl estradiol on activities of various aminotransferases or their saturation with the PLP cofactor in experimental animals are controversial, most likely due to species-, organ-and subcellular-specific differences and type of sex steroid. [66][67][68][69][70] For example, whereas E2 and ethinyl estradiol may inhibit, progestogens stimulate these enzymes. In humans, this is illustrated by the absence of an effect of a combination of norgestrel and ethinyl estradiol on alanine aminotransferase or aspartate aminotransferase.…”

Section: Effects Of Estrogens On Brain Serotonin Synthesis and Functionmentioning

confidence: 99%

Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents

Badawy

2018

Int J�Tryptophan�Res

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Modulation of tryptophan (Trp) metabolism may underpin the behavioral effects of androgenic-anabolic steroids (AAS) and associated image and performance enhancers. Euphoria, arousal, and decreased anxiety observed with moderate use and exercise may involve enhanced cerebral serotonin synthesis and function by increased release of albumin-bound Trp and estrogen-mediated liver Trp 2,3-dioxygenase (TDO) inhibition and enhancement of serotonin function. Aggression, anxiety, depression, personality disorders, and psychosis, observed on withdrawal of AAS or with use of large doses, can be caused by decreased serotonin synthesis due to TDO induction on withdrawal, excess Trp inhibiting the 2 enzymes of serotonin synthesis, and increased cerebral levels of neuroactive kynurenines. Exercise and excessive protein and branched-chain amino acid intakes may aggravate the effects of large AAS dosage. The hypothesis is testable in humans and experimental animals by measuring parameters of Trp metabolism and disposition and related metabolic processes.

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“…Between 1959 and 1976, a small number of studies were done examining the effects of estradiol analogues on the activity of the kynurenine aminotransferase isozymes. One study showed that β-estradiol ( 81 ) and ethynylestradiol ( 82 ), shown in Figure 22 , could inhibit the activity of male mice KATs [ 62 ].…”

Section: Kynurenine Aminotransferases Inhibitorsmentioning

confidence: 99%

Kynurenine Aminotransferase Isozyme Inhibitors: A Review

Nematollahi

Sun

Jayawickrama

et al. 2016

IJMS

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Kynurenine aminotransferase isozymes (KATs 1–4) are members of the pyridoxal-5’-phosphate (PLP)-dependent enzyme family, which catalyse the permanent conversion of l-kynurenine (l-KYN) to kynurenic acid (KYNA), a known neuroactive agent. As KATs are found in the mammalian brain and have key roles in the kynurenine pathway, involved in different categories of central nervous system (CNS) diseases, the KATs are prominent targets in the quest to treat neurodegenerative and cognitive impairment disorders. Recent studies suggest that inhibiting these enzymes would produce effects beneficial to patients with these conditions, as abnormally high levels of KYNA are observed. KAT-1 and KAT-3 share the highest sequence similarity of the isozymes in this family, and their active site pockets are also similar. Importantly, KAT-2 has the major role of kynurenic acid production (70%) in the human brain, and it is considered therefore that suitable inhibition of this isozyme would be most effective in managing major aspects of CNS diseases. Human KAT-2 inhibitors have been developed, but the most potent of them, chosen for further investigations, did not proceed in clinical studies due to the cross toxicity caused by their irreversible interaction with PLP, the required cofactor of the KAT isozymes, and any other PLP-dependent enzymes. As a consequence of the possibility of extensive undesirable adverse effects, it is also important to pursue KAT inhibitors that reversibly inhibit KATs and to include a strategy that seeks compounds likely to achieve substantial interaction with regions of the active site other than the PLP. The main purpose of this treatise is to review the recent developments with the inhibitors of KAT isozymes. This treatise also includes analyses of their crystallographic structures in complex with this enzyme family, which provides further insight for researchers in this and related studies.

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In vitro Trials to counteract the inhibitory effect of β-oestradiol and ethynyloestradiol on the B6-dependent kynurenine aminotransferase enzyme

Cited by 4 publications

References 11 publications

Tryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention

Tryptophan Metabolism: A Versatile Area Providing Multiple Targets for Pharmacological Intervention

Modulation of Tryptophan and Serotonin Metabolism as a Biochemical Basis of the Behavioral Effects of Use and Withdrawal of Androgenic-Anabolic Steroids and Other Image- and Performance-Enhancing Agents

Kynurenine Aminotransferase Isozyme Inhibitors: A Review

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