Next Article in Journal
The Effect of MCP-1/CCR2 on the Proliferation and Senescence of Epidermal Constituent Cells in Solar Lentigo
Previous Article in Journal
Comprehensive and Quantitative Proteomic Analysis of Metamorphosis-Related Proteins in the Veined Rapa Whelk, Rapana venosa
Article Menu
Issue 6 (June) cover image

Export Article

Open AccessReview
Int. J. Mol. Sci. 2016, 17(6), 946;

Kynurenine Aminotransferase Isozyme Inhibitors: A Review

Group in Biomolecular Structure and Informatics, Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia
Authors to whom correspondence should be addressed.
Academic Editor: Terrence Piva
Received: 11 May 2016 / Revised: 8 June 2016 / Accepted: 10 June 2016 / Published: 15 June 2016
(This article belongs to the Section Biochemistry)


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. View Full-Text
Keywords: kynurenine aminotransferase; pyridoxal 5′-phosphate; cognitive disorders; schizophrenia; KYNA kynurenine aminotransferase; pyridoxal 5′-phosphate; cognitive disorders; schizophrenia; KYNA

Figure 1

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 (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Nematollahi, A.; Sun, G.; Jayawickrama, G.S.; Church, W.B. Kynurenine Aminotransferase Isozyme Inhibitors: A Review. Int. J. Mol. Sci. 2016, 17, 946.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top