D-Glutamate is metabolized in the heart mitochondria

被引：55

作者：

Ariyoshi, Makoto ^{[1
]}

Katane, Masumi ^{[2
]}

Hamase, Kenji ^{[3
]}

Miyoshi, Yurika ^{[3
]}

Nakane, Maiko ^{[4
]}

Hoshino, Atsushi ^{[1
]}

Okawa, Yoshifumi ^{[1
]}

Mita, Yuichiro ^{[1
]}

Kaimoto, Satoshi ^{[1
]}

Uchihashi, Motoki ^{[1
]}

Fukai, Kuniyoshi ^{[1
]}

Ono, Kazunori ^{[1
]}

Tateishi, Syuhei ^{[1
]}

Hato, Daichi ^{[1
]}

Yamanaka, Ryoetsu ^{[1
]}

Honda, Sakiko ^{[1
]}

Fushimura, Yohei ^{[1
]}

Iwai-Kanai, Eri ^{[1
,5
]}

Ishihara, Naotada ^{[6
]}

Mita, Masashi ^{[4
]}

Homma, Hiroshi ^{[2
]}

Matoba, Satoaki ^{[1
]}

机构：

[1] Kyoto Prefectural Univ Med, Grad Sch Med Sci, Dept Cardiovasc Med, Kamigyo Ku, Kyoto 6028566, Japan

[2] Kitasato Univ, Grad Sch Pharmaceut Sci, Lab Biomol Sci, Minato Ku, 5-9-1 Shirokane, Tokyo 1088641, Japan

[3] Kyushu Univ, Grad Sch Pharmaceut Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan

[4] Shiseido Co Ltd, Minato Ku, 1-1-16 Higashi Shimbashi, Tokyo 1050021, Japan

[5] Tenri Hlth Care Univ, Fac Hlth Care, 80-1 Bessho Cho, Tenri, Nara 6320018, Japan

[6] Kurume Univ, Inst Life Sci, Dept Prot Biochem, 1-1 Hyakunen Koen, Kurume, Fukuoka 8390864, Japan

来源：

SCIENTIFIC REPORTS | 2017年 / 7卷

关键词：

PYRROLIDONE CARBOXYLIC-ACID; D-ASPARTIC ACID; D-AMINO ACIDS; SERINE RACEMASE; D-GLUTAMATE; MAMMALS; BIOSYNTHESIS; INHIBITION;

D O I：

10.1038/srep43911

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

(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.

引用

页数：9

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