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Role of Glutamine Transaminases in Nitrogen, Sulfur, Selenium, and 1-Carbon Metabolism

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Glutamine in Clinical Nutrition

Part of the book series: Nutrition and Health ((NH))

Abstract

Glutamine metabolism is largely controlled by two enzyme pathways: 1) Conversion of glutamine to glutamate catalyzed by glutaminases, followed by conversion of glutamate to α-ketoglutarate by a glutamate-linked aminotransferases (or by the action of glutamate dehydrogenase); and 2) conversion of glutamine to α-ketoglutaramate (KGM) catalyzed by glutamine-utilizing transaminases (aminotransferases), followed by conversion of KGM to α-ketoglutarate by the action of ω-amidase. The former pathway has been well documented and intensively studied for over 60 years, whereas only recently has research focused on the latter pathway, its importance in homeostasis and the control of anaplerotic metabolites. The glutamine transaminases are of fundamental importance 1) as repair enzymes (salvage of α-keto acids), 2) in nitrogen and sulfur homeostasis (closure of the methionine salvage pathway), 3) in 1-carbon metabolism, and 4) in metabolism of seleno amino acids. As a result of their broad substrate specificity the two principal mammalian glutamine transaminases (i.e. glutamine transaminases L and K) have also been characterized as kynurenine aminotransferases (KAT I and KAT III, respectively), responsible for the production of neuroactive kynurenate. The glutamine transaminases are also active with a variety of sulfur- and selenium-containing amino acids. Some of the products derived from the transamination of these amino acids may also be neuroactive (e.g. certain sulfur-containing cyclic ketimines) as well as chemopreventive (e.g. the α-keto acids derived from seleno amino acids). Of relevance to human health and disease, the glutamine transaminases may contribute to the bioactivation (toxification) of halogenated alkenes (and possibly other xenobiotic electrophiles), some of which are environmental contaminants. Finally, the role of the glutamine transaminases and ω-amidase in cancer biology has been little studied. However, the “glutamine addiction” of many tumors suggests that the glutamine transaminases together with ω-amidase may have a fundamental and influential role in regulating cancer progression

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Acknowledgements

Part of the work from our laboratories cited in this chapter was supported by NIH grants CA111842 (to JTP) and ES008421 (to AJLC).

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Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY, USA

    Arthur J. L. Cooper Ph.D., D.Sc., Boris F. Krasnikov Ph.D. & John Thomas Pinto Ph.D.

  2. Department of Urology, New York Medical College, Valhalla, NY, USA

    Thambi Dorai Ph.D.

  3. Department of Pathology, Nyack Hospital, Nyack, NY, USA

    Bhuvaneswari Dorai M.D.

  4. Department of Biochemistry, Virginia Tech, Blacksburg, VA, USA

    Jianyong Li D.V.M., Ph.D.

  5. Department of Chemistry and Biomolecular Sciences, Macquarie University, Balaclava Road, North Ryde, Australia

    André Hallen B.Sc.

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  1. Arthur J. L. Cooper Ph.D., D.Sc.
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  3. Bhuvaneswari Dorai M.D.
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Correspondence to Arthur J. L. Cooper Ph.D., D.Sc. .

Editor information

Editors and Affiliations

  1. Department of Intensive Care, Barnet and Chase Farm Hospitals, London, United Kingdom

    Rajkumar Rajendram

  2. Department of Nutrition and Dietetics, Diabetes and Nutritional Sciences, School of Medicine, King’s College London, London, United Kingdom

    Victor R. Preedy

  3. Department of Biomedical Sciences, University of Westminster, London, United Kingdom

    Vinood B. Patel

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Cooper, A.J.L. et al. (2015). Role of Glutamine Transaminases in Nitrogen, Sulfur, Selenium, and 1-Carbon Metabolism. In: Rajendram, R., Preedy, V., Patel, V. (eds) Glutamine in Clinical Nutrition. Nutrition and Health. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-1932-1_3

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  • DOI: https://doi.org/10.1007/978-1-4939-1932-1_3

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