Molecular characterization of N-acetylaspartylglutamate synthetase.

The Journal of Biological Chemistry
Ivonne BeckerMatthias Eckhardt

Abstract

The dipeptide N-acetylaspartyl-glutamate (NAAG) is an abundant neuropeptide in the mammalian brain. Despite this fact, its physiological role is poorly understood. NAAG is synthesized by a NAAG synthetase catalyzing the ATP-dependent condensation of N-acetylaspartate and glutamate. In vitro NAAG synthetase activity has not been described, and the enzyme has not been purified. Using a bioinformatics approach we identified a putative dipeptide synthetase specifically expressed in the nervous system. Expression of the gene, which we named NAAGS (for NAAG synthetase) was sufficient to induce NAAG synthesis in primary astrocytes or CHO-K1 and HEK-293T cells when they coexpressed the NAA transporter NaDC3. Furthermore, coexpression of NAAGS and the recently identified N-acetylaspartate (NAA) synthase, Nat8l, in CHO-K1 or HEK-293T cells was sufficient to enable these cells to synthesize NAAG. Identity of the reaction product of NAAGS was confirmed by HPLC and electrospray ionization tandem mass spectrometry (ESI-MS). High expression levels of NAAGS were restricted to the brain, spinal cord, and testis. Taken together our results strongly suggest that the identified gene encodes a NAAG synthetase. Its identification will enable further...Continue Reading

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Citations

Feb 4, 2011·Proceedings of the National Academy of Sciences of the United States of America·Zachary J ReitmanHai Yan
May 2, 2013·Journal of Neuroscience Research·Prasanth S AriyannurAryan M A Namboodiri
Jul 31, 2013·The Biochemical Journal·Julia Lodder-GadaczekMatthias Eckhardt
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Oct 12, 2017·The International Journal of Neuropsychopharmacology·Yoshiaki MiyamotoAtsumi Nitta
Nov 9, 2017·Acta Neuropathologica·Georg von JonquieresMatthias Klugmann
Apr 2, 2011·The Journal of Biological Chemistry·Julia Lodder-GadaczekMatthias Eckhardt
May 23, 2018·The International Journal of Neuropsychopharmacology·Jinsong TangEdythe D London
Jun 20, 2017·Frontiers in Molecular Neuroscience·Abhilash P AppuAryan M A Namboodiri
Feb 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Carmen Jiménez-EspinozaJosé Luis González-Mora
Feb 28, 2021·Journal of Neurochemistry·Ivonne BeckerMatthias Eckhardt
Jun 9, 2021·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Hajime MiyanishiAtsumi Nitta

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