Involvement of Spermidine in the Reduced Lifespan of During Vitamin B Deficiency.

Vitamin B deficiency leads to various symptoms such as neuropathy, growth retardation, and infertility. Vitamin B 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 B deficiency induce such symptoms. First, free amino acid levels were determined in vitamin B-deficient to clarify the mechanisms underlying the symptoms caused by vitamin B deficiency. Various amino acids (valine, leucine, isoleucine, methionine, and cystathionine, among others) metabolized by vitamin B-dependent enzymes were found to be significantly changed during conditions of B deficiency, which indirectly affected certain amino acids metabolized by vitamin B-independent enzymes. For example, ornithine was significantly increased during vitamin B deficiency, which also significantly increased arginase activity. The accumulation of ornithine during vitamin B deficiency constitutes the first report. In addition, the biosynthesis of spermidine from ornithine was significantly decreased during vitamin B deficiency, likely due to the reduction of -adenosylmethionine as a substrate for -adenosylmethionine decarboxylase, which catalyzes the formation of spermidine. Moreover, vitamin B 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 B-deficient worms.