Role of D-amino acid in adaptation of organisms to environmental change

D-氨基酸在生物体适应环境变化中的作用

基本信息

批准号：
11691187
负责人：
YOSHIMURA Tohru
金额：
$ 4.93万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11691187/
关键词：
D-amino acid alanine racemase D-aminoacid oxidase osmolite ラセマーゼ

项目摘要

After the finding that D-serine serves as an agonist of NMDA receptor of a mammalian brain, role of D-amino acids in eucaryotes has been received an increased attention. The fresh water crayfish has been reported to accumulate total free D-alanine by more than 30-fold in muscle after seawater acclimation. We are interested in the realtionship between D-amino acids and the environmental stress, and studied the enzymes related to the D-amino acid metabolism in eucaryotes. We found the alanine racemase from the hepatopancreas of the black tiger prawn, Penaeus monodon. The prawn enzyme is distinguishable immunochemically from bacterial enzymes and differs from fungal enzymes in the moleular weight and subunit structure. Monovalent anions including chloride are involved in the regulation of the enzyme through stabilization and activation. This is consistent with the hypothesis that D-alanine serves as an osmoregulator in marine and euryhaline animals. We also found that the silkworm has serine racemase which has similar properties to the rat brain serine racemase in pH optimum, substrate specificity, and behaviors upon chromatographies. At the stage of pupation, the contents of D-serine increased concomitantly with the increase in this enzymatic activity. In this work, we also studied the three amino acid racemases of Schizosaccharomyces pombe, Alr1p, Alr2p, and Srf1p. Alr1p is a homologs of bacterial alanine racemase. A1r2p is a fission yeast counterpart to bacterial arginine racemase, and Srf1p resembles a rat serine racemase in low catalytic efficiency. These racemases are probably involved in the detoxification of D-amino acids. In this work, we also performed the screening of new enzymes involved in the D-amino acid metabolism in marine and euryhaline animals in Australia and the United States.

在发现D-丝氨酸作为哺乳动物大脑NMDA受体的激动剂后，D-氨基酸在真核生物中的作用受到越来越多的关注。据报道，淡水小龙虾在海水适应后，其肌肉中总游离 D-丙氨酸的积累量增加了 30 倍以上。我们对D-氨基酸与环境胁迫之间的关系感兴趣，并研究了真核生物中与D-氨基酸代谢相关的酶。我们从黑虎虾斑节对虾的肝胰腺中发现了丙氨酸消旋酶。虾酶在免疫化学上与细菌酶有区别，并且在分子量和亚基结构上与真菌酶不同。包括氯在内的单价阴离子通过稳定和激活参与酶的调节。这与 D-丙氨酸在海洋和广盐动物中充当渗透压调节剂的假设是一致的。我们还发现家蚕含有丝氨酸消旋酶，其在最适pH、底物特异性和色谱行为方面与大鼠脑丝氨酸消旋酶具有相似的特性。在化蛹阶段，D-丝氨酸的含量随着该酶活性的增加而增加。在这项工作中，我们还研究了粟酒裂殖酵母的三种氨基酸消旋酶：Alr1p、Alr2p 和 Srf1p。 Alr1p 是细菌丙氨酸消旋酶的同源物。 A1r2p 是细菌精氨酸消旋酶的裂殖酵母对应物，Srf1p 类似于大鼠丝氨酸消旋酶，但催化效率较低。这些消旋酶可能参与 D-氨基酸的解毒。在这项工作中，我们还在澳大利亚和美国的海洋和广盐动物中筛选了参与 D-氨基酸代谢的新酶。