(D)-Glutamate is metabolized in the heart mitochondria.
(D)-Glutamate is metabolized in the heart mitochondria.
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DOI：
10.1038/srep43911
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发表时间：
2017-03-07
影响因子：
4.6
通讯作者：
Matoba S
中科院分区：
文献类型：
--
作者：
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;Mita M;Homma H;Matoba S
D-氨基酸是L-氨基酸的对映体，最近被认为是哺乳动物（包括人类）的生物标志物和生物活性物质。在本研究中，我们研究了新的哺乳动物线粒体蛋白9030617 O 03 Rik的功能，并显示心力衰竭条件下表达下降。基因组序列分析显示与细菌天冬氨酸/谷氨酸/乙内酰脲消旋酶部分同源。随后对9030617 O 03 Rik缺陷小鼠的所有游离氨基酸浓度进行测定，结果显示心脏组织中D-谷氨酸的大量积累。这是第一次在哺乳动物组织中检测到大量的D-谷氨酸。对D-谷氨酸代谢的进一步分析表明，9030617 O 03 Rik是一种D-谷氨酸环化酶，可将D-谷氨酸转化为5-氧代-D-脯氨酸。因此，这种蛋白质是第一个确定的负责哺乳动物D-谷氨酸代谢的酶，在克隆分析中得到证实。这些结果表明，D-谷氨酸和5-氧代-D-脯氨酸在哺乳动物体内通过D-谷氨酸环化酶代谢而具有生物活性。
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.