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Open AccessArticle

Involvement of Spermidine in the Reduced Lifespan of Caenorhabditis elegans During Vitamin B12 Deficiency

Department of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, Japan
The United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, Japan
Author to whom correspondence should be addressed.
Metabolites 2019, 9(9), 192;
Received: 27 August 2019 / Revised: 12 September 2019 / Accepted: 18 September 2019 / Published: 19 September 2019
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. View Full-Text
Keywords: arginase; Caenorhabditis elegans; ornithine; spermidine; vitamin B12 arginase; Caenorhabditis elegans; ornithine; spermidine; vitamin B12
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Bito, T.; Okamoto, N.; Otsuka, K.; Yabuta, Y.; Arima, J.; Kawano, T.; Watanabe, F. Involvement of Spermidine in the Reduced Lifespan of Caenorhabditis elegans During Vitamin B12 Deficiency. Metabolites 2019, 9, 192.

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