D-Glutamate is metabolized in the heart mitochondria

Makoto Ariyoshi, Masumi Katane, Kenji Hamase, Yurika Miyoshi, Maiko Nakane, Atsushi Hoshino, Yoshifumi Okawa, Yuichiro Mita, Satoshi Kaimoto, Motoki Uchihashi, Kuniyoshi Fukai, Kazunori Ono, Syuhei Tateishi, Daichi Hato, Ryoetsu Yamanaka, Sakiko Honda, Yohei Fushimura, Eri Iwai-Kanai, Naotada Ishihara, Masashi MitaHiroshi Homma, Satoaki Matoba

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Abstract

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.

Original languageEnglish
Article number43911
JournalScientific reports
Volume7
DOIs
Publication statusPublished - Mar 7 2017

All Science Journal Classification (ASJC) codes

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    Ariyoshi, M., Katane, M., Hamase, K., Miyoshi, Y., Nakane, M., Hoshino, A., Okawa, Y., Mita, Y., Kaimoto, S., Uchihashi, M., Fukai, K., Ono, K., Tateishi, S., Hato, D., Yamanaka, R., Honda, S., Fushimura, Y., Iwai-Kanai, E., Ishihara, N., ... Matoba, S. (2017). D-Glutamate is metabolized in the heart mitochondria. Scientific reports, 7, [43911]. https://doi.org/10.1038/srep43911