Studies of bio-regulation with D-amino acids and its application

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04908
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied biochemistry
• Research Institution: Nagoya University
• Principal Investigator: Yoshimura Tohru 名古屋大学, 生命農学研究科, 教授 (70182821)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: D-アミノ酸 / D-セリン / セリンラセマーゼ / D-セリンデヒドラターゼ / 腎疾患マーカー

Outline of Final Research Achievements

The goal of this study is to clarify the metabolism and physiological functions of D-amino acids, and their application to various research tools. The following studies were conducted. 1) Serine racemase, which is responsible for the biosynthesis of D-Ser, a co-agonist of NMDA receptor, was confirmed to catalyze the D-serine dehydration. 2) An unknown D-amino acid was found in an edible mushroom, Hypsizygus marmoreus, and identified as D-2-amino-3,4-dihydroxy-butanoic acid. (3) Urinary D-Ser concentrations of renal disease patients and healthy subjects were analyzed. Ratio of the urinary D-Ser concentration to that of urinary creatinine was suggested to serve as a biomarker of renal disorder. (4) Functional cloning system of the genes encoding D-amino acid synthesizing enzymes was constructed with E. coli mutant lacking alanine racemase and glutamate racemase genes.

Free Research Field

生物化学

Academic Significance and Societal Importance of the Research Achievements

D-アミノ酸の生理機能が注目されている。例えば D-Serは記憶や学習などの脳機能に、D-Aspは脳ホルモンの分泌などに関与する。本研究では D-アミノ酸の機能や代謝の解明、様々な研究ツールへの応用を試みた。具体的には、D-Ser合成を担うセリンラセマーゼがD-Serの分解にも働くこと、ブナシメジに新奇D-アミノ酸、D-2-amino-3,4-dihydroxy-butanoic acidが存在すること、尿中のD-Serとクレアチニンの濃度比が腎疾患マーカーへ応用可能であることを示した。また D-アミノ酸研究の強力なツールとなるD-アミノ酸生合成酵素遺伝子スクリーニング系を構築した。