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Sci Rep. 2017 Mar 7;7:43911. doi: 10.1038/srep43911.

D-Glutamate is metabolized in the heart mitochondria.

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Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Laboratory of Biomolecular Science, Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Shiseido Co., Ltd., 1-1-16 Higashi-shimbashi, Minato-ku, Tokyo 105-0021, Japan.
Faculty of Health Care, Tenri Health Care University, 80-1 Bessho-cho, Tenri, Nara 632-0018, Japan.
Department of Protein Biochemistry, Institute of Life Science, Kurume University, 1-1 Hyakunen-koen, Kurume 839-0864, Japan.


D-Amino acids are enantiomers of L-amino acids and have recently been recognized as biomarkers and bioactive substances in mammals, including humans. In the present study, we investigated functions of the novel mammalian mitochondrial protein 9030617O03Rik and showed decreased expression under conditions of heart failure. Genomic sequence analyses showed partial homology with a bacterial aspartate/glutamate/hydantoin racemase. Subsequent determinations of all free amino acid concentrations in 9030617O03Rik-deficient mice showed high accumulations of D-glutamate in heart tissues. This is the first time that a significant amount of D-glutamate was detected in mammalian tissue. Further analysis of D-glutamate metabolism indicated that 9030617O03Rik is a D-glutamate cyclase that converts D-glutamate to 5-oxo-D-proline. Hence, this protein is the first identified enzyme responsible for mammalian D-glutamate metabolism, as confirmed in cloning analyses. These findings suggest that D-glutamate and 5-oxo-D-proline have bioactivities in mammals through the metabolism by D-glutamate cyclase.

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