Elucidation of myocardial amino acid metabolic regulation by novel mitochondrial protein and the development to treat for heart failure

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K09144
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Matoba Satoaki 京都府立医科大学, 医学(系)研究科(研究院), 教授 (10305576)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 心不全 / ミトコンドリア / エネルギー代謝 / キラルアミノ酸 / Ｄアミノ酸 / Ｄグルタミン酸 / Ｄグルタミン酸サイクラーゼ / アミノ酸代謝

Outline of Final Research Achievements

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.

Free Research Field

循環器内科学