A novel function of tryptophan key enzyme in the brain and its regulation mechanism

α-氨基-β-羧酸-ε半醛脱羧酶在色氨酸生物合成过程中起着关键作用。ACMSD似乎也影响了色氨酸生成喹啉酸盐。喹诺酯是一种强效的神经细胞内源性兴奋性毒素。在这项研究中，我们考察了食物成分、激素或药物对喹啉酸生产的影响。给大鼠饲喂含有试验材料的饲料8天后，植物油、鱼油、高蛋白或过氧化物酶增殖剂通过抑制ACMSD基因的表达和活性而影响喹啉酸的产生。肝、肾ACMSD活性总和与喹啉酸浓度呈负相关。我们还显示了吡津酰胺和过氧化物酶体增殖剂对大鼠ACMSD基因表达的不同影响。ACMSD的转录水平受多不饱和脂肪酸和过氧化物酶体增殖物的调控，ACMSD的表达随ACMSD活性的变化而变化。但是，吡津酰胺不影响ACMSD的转录水平。我们还发现，多不饱和脂肪酸对肝细胞中ACMSD的下调不是由过氧化物酶体增殖物激活受体(PPAR)α介导的。接下来，我们研究了ACMSD在大脑中的定位。应用原位杂交技术，观察ACMSD基因在大鼠海马或小脑的定位表达。

α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD) plays a key role in regulating NAD biosynthesis from tryptophan. ACMSD also seems to affect the generation of quinolinate from tryptophan. Qunolinate is a potent endogenous excitotoxin of neuronal cells. In this study, we examined the effect of food components, hormone or medicine on quinolinic acid production. When diets containing test materials were given to rats for 8 days, dietary plant oil, fish oil, high protein or peroxisome proliferators affected quinolinic acid production by suppressing ACMSD mRNA expression and activity. There was the negative correlation between the sum of liver and kidney ACMSD activities, and the quinolinic acid concentration. We also showed differential effects of pyrazinamide and peroxisome proliferators on gene expression of rat ACMSD. The transcription level of ACMSD is modulated by polyunsaturated fatty acid and peroxisome proliferators, and the fluctuation of the ACMSD expression was followed by that of the ACMSD activity. However pyrazinamide does not affect the transcription level of ACMSD. We also showed down-regulation of ACMSD by polyunsatu-rated fatty acids in hepatocytes is not mediated by peroxisome proliferator-activated receptor (PPAR) α. Next we examined the localization of ACMSD in the brain. Using in situ hybridization, localization ACMSD mRNA expressing hippocampus or cerebellum was observed.