The novel function of a key enzyme regulating tryptophan-NAD metabolism

色氨酸-NAD代谢关键酶的新功能

• 批准号: 13660118
• 负责人: EGASHIRA Yukari
• 金额: $ 2.24万
• 依托单位: Chiba University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13660118/
• 关键词: tryptophan; niacin; immunity; ACMSD; rat; quinolinate; picolinate; linoleic acid; マウス

Picolinate has been implicated in immune system in vitro experiments. On the other hand, quinolinate is a potent endogenous excitotoxin of neuronal cells. α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD ; EC 4.1.1.45) is one of the important enzymes regulating tryptophan-niacin metabolism. ACMSD seems to be able to influence directly the production of picolinate and quinolinate. In this study, we investigated the effect of acute immune stimulation on ACMSD activity and mRNA expression in rats. ACMSD mRNA was expressed in the liver and kidney, but not in the brain, lung, spleen and thymus by RT-PCR in control and LPS-treated groups. There were no significant difference between control and LPS treated rats in ACMSD activity and mRNA. Moreover we measured the tryptophan catabolite quinolinic acid level in rats fed on linoleic acid. In rats fed with 10 or 20% linoleic acid diet, ACMSD mRNA in the liver was strongly suppressed and serum quinolinic acid was significantly increased as compared with the rats fed on a fat-free diet. These results suggest that there is an inverse relationship between ACMSD activity and the production of quinolinic acid converted from tryptophan.

在体外实验中，吡啶甲酸酯与免疫系统有关。另一方面，喹啉酸是神经细胞的强内源性兴奋性毒素。α-氨基-β-羧基粘康酸-ε-半醛脱羧酶（α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase，ACMSD ; EC 4.1.1.45）是调节烟酸代谢的重要酶。ACMSD似乎能够直接影响吡啶甲酸和喹啉甲酸的生产。本研究探讨了急性免疫刺激对大鼠ACMSD活性和mRNA表达的影响。RT-PCR结果显示，对照组和LPS处理组ACMSD mRNA在肝、肾中均有表达，而在脑、肺、脾和胸腺中无表达。对照组和LPS组大鼠ACMSD活性和mRNA表达无显著性差异。此外，我们还测量了喂食亚油酸的大鼠中的色氨酸分解代谢物喹啉酸水平。与无脂饲料喂养的大鼠相比，10%或20%亚油酸饲料喂养的大鼠肝脏中ACMSD mRNA被强烈抑制，血清喹啉酸显著升高。这些结果表明，ACMSD活性和色氨酸转化为喹啉酸的产量之间存在反比关系。

项目成果

Fukuoka SI et al.: "Identification and expression of a cDNA encoding human alpha-amino-beta-carboxymuconate-epsilon-semialdehyde decarboxylase (ACMSD). A key enzyme for the tryptophan-niacine pathway and "quinolinate hypothesis""J. Biol. Chem.. 277・38. 35

Fukuoka SI 等人：“编码人 α-氨基-β-羧基粘康酸-ε-半醛脱羧酶 (ACMSD) 的 cDNA 的鉴定和表达。色氨酸-烟酸途径和“喹啉酸假说”的关键酶”J. Biol。化学.. 277・38.

江頭 祐嘉合, 笹原祥吾, 真田宏夫: "トリプトファン・ナイアシン代謝の鍵酵素α-アミノ-β-カルボキシムコン酸-ε-セミアルデヒド脱炭酸酵素(ACMSD)と免疫との関連"健康創造研究会誌. 3・1(in press). (2004)

Yukago Egashira、Shogo Sasahara、Hiroo Sanada：“色氨酸和烟酸代谢中的关键酶 α-氨基-β-羧基粘康酸-ε-半醛脱羧酶 (ACMSD) 与免疫之间的关系”健康创造研究会杂志 3。・1（正在出版）（2004）。

A.Tanabe: "Purification and molecular cloning of rat 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase."Biochem.J.. 361. 567-575 (2002)

A.Tanabe：“大鼠 2-氨基-3-羧基粘康酸-6-半醛脱羧酶的纯化和分子克隆。”Biochem.J.. 361. 567-575 (2002)

A.Tanabe: "Expression of rat hepatic 2-amino-3-carboxymuconate-6-semialdehyde decarboxylase is affected by a high protein diet and by streptozotocin-induced diabetes."J.Nutr.. 132. 1153-1159 (2002)

A.Tanabe：“大鼠肝脏 2-氨基-3-羧基粘康酸-6-半醛脱羧酶的表达受到高蛋白饮食和链脲佐菌素诱导的糖尿病的影响。”J.Nutr.. 132. 1153-1159 (2002)

S.Fukuoka: "Identification and expression of a cDNA encoding human ACMSD : a key enzyme for the tryptophan-niacine pathway and quinolinate hypothesis."J.Biol.Chem.. 277. 35162-35167 (2002)

S.Fukuoka：“编码人 ACMSD 的 cDNA 的鉴定和表达：色氨酸烟酸途径和喹啉酸假说的关键酶。”J.Biol.Chem.. 277. 35162-35167 (2002)