Metabolites · Sep 19, 2019

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

By Bito T, Okamoto N, Otsuka K et al.

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.

doi.org/10.3390/metabo9090192Open accessPubMed 31546940Interventions