Involvement of Spermidine in the Reduced Lifespan of Caenorhabditis elegans During Vitamin B12 Deficiency
Involvement of Spermidine in the Reduced Lifespan of Caenorhabditis elegans During Vitamin B12 Deficiency
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DOI：
10.3390/metabo9090192
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发表时间：
2019-09
期刊：
影响因子：
4.1
通讯作者：
T. Bito;Naho Okamoto;Kenji Otsuka;Y. Yabuta;J. Arima;T. Kawano;F. Watanabe
中科院分区：
文献类型：
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作者：
T. Bito;Naho Okamoto;Kenji Otsuka;Y. Yabuta;J. Arima;T. Kawano;F. Watanabe
维生素B12缺乏会导致神经病变、生长迟缓、不孕等多种症状。维生素 B12 作为参与氨基酸代谢的两种酶的辅酶。然而，关于维生素 B12 缺乏引起的氨基酸紊乱是否会引起此类症状的信息有限。首先，测定了缺乏维生素 B12 的秀丽隐杆线虫中的游离氨基酸水平，以阐明维生素 B12 缺乏引起的症状的机制。研究发现，维生素 B12 依赖性酶代谢的各种氨基酸（缬氨酸、亮氨酸、异亮氨酸、蛋氨酸和胱硫醚等）在维生素 B12 缺乏的情况下发生显着变化，从而间接影响了非维生素 B12 依赖性酶代谢的某些氨基酸。例如，维生素 B12 缺乏时鸟氨酸显着增加，精氨酸酶活性也显着增加。维生素 B12 缺乏期间鸟氨酸的积累构成了第一份报告。此外，在维生素 B12 缺乏期间，从鸟氨酸生物合成亚精胺的能力显着降低，这可能是由于作为 S-腺苷甲硫氨酸脱羧酶底物的 S-腺苷甲硫氨酸减少，该酶催化亚精胺的形成。此外，维生素 B12 缺乏也会显着缩短蠕虫的寿命，但通过添加亚精胺可以部分恢复这一寿命。总的来说，我们的研究结果表明，亚精胺减少是导致缺乏维生素 B12 的线虫寿命缩短的因素之一。
Vitamin B12 deficiency leads to various symptoms such as neuropathy, growth retardation, and infertility. Vitamin B12 functions as a coenzyme for two enzymes involved in amino acid metabolisms. However, there is limited information available on whether amino acid disorders caused by vitamin B12 deficiency induce such symptoms. First, free amino acid levels were determined in vitamin B12-deficient Caenorhabditis elegans to clarify the mechanisms underlying the symptoms caused by vitamin B12 deficiency. Various amino acids (valine, leucine, isoleucine, methionine, and cystathionine, among others) metabolized by vitamin B12-dependent enzymes were found to be significantly changed during conditions of B12 deficiency, which indirectly affected certain amino acids metabolized by vitamin B12-independent enzymes. For example, ornithine was significantly increased during vitamin B12 deficiency, which also significantly increased arginase activity. The accumulation of ornithine during vitamin B12 deficiency constitutes the first report. In addition, the biosynthesis of spermidine from ornithine was significantly decreased during vitamin B12 deficiency, likely due to the reduction of S-adenosylmethionine as a substrate for S-adenosylmethionine decarboxylase, which catalyzes the formation of spermidine. Moreover, vitamin B12 deficiency also demonstrated a significant reduction in worm lifespan, which was partially recovered by the addition of spermidine. Collectively, our findings suggest that decreased spermidine is one factor responsible for reduced lifespan in vitamin B12-deficient worms.