Involvement of Spermidine in the Reduced Lifespan of <i>Caenorhabditis elegans</i> During Vitamin B<sub>12</sub> Deficiency
Vitamin B<sub>12</sub> deficiency leads to various symptoms such as neuropathy, growth retardation, and infertility. Vitamin B<sub>12</sub> functions as a coenzyme for two enzymes involved in amino acid metabolisms. However, there is limited information available on whether a...
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MDPI AG
2019-09-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/9/9/192 |
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| author | Tomohiro Bito Naho Okamoto Kenji Otsuka Yukinori Yabuta Jiro Arima Tsuyoshi Kawano Fumio Watanabe |
| author_facet | Tomohiro Bito Naho Okamoto Kenji Otsuka Yukinori Yabuta Jiro Arima Tsuyoshi Kawano Fumio Watanabe |
| author_sort | Tomohiro Bito |
| collection | DOAJ |
| description | Vitamin B<sub>12</sub> deficiency leads to various symptoms such as neuropathy, growth retardation, and infertility. Vitamin B<sub>12</sub> 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<sub>12</sub> deficiency induce such symptoms. First, free amino acid levels were determined in vitamin B<sub>12</sub>-deficient <i>Caenorhabditis elegans</i> to clarify the mechanisms underlying the symptoms caused by vitamin B<sub>12</sub> deficiency. Various amino acids (valine, leucine, isoleucine, methionine, and cystathionine, among others) metabolized by vitamin B<sub>12</sub>-dependent enzymes were found to be significantly changed during conditions of B<sub>12</sub> deficiency, which indirectly affected certain amino acids metabolized by vitamin B<sub>12</sub>-independent enzymes. For example, ornithine was significantly increased during vitamin B<sub>12</sub> deficiency, which also significantly increased arginase activity. The accumulation of ornithine during vitamin B<sub>12</sub> deficiency constitutes the first report. In addition, the biosynthesis of spermidine from ornithine was significantly decreased during vitamin B<sub>12</sub> deficiency, likely due to the reduction of <i>S</i>-adenosylmethionine as a substrate for <i>S</i>-adenosylmethionine decarboxylase, which catalyzes the formation of spermidine. Moreover, vitamin B<sub>12</sub> 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<sub>12</sub>-deficient worms. |
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| language | English |
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| publishDate | 2019-09-01 |
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| spelling | doaj.art-a02cea6b30a44fafa8d7a91ba05b08132022-12-22T01:26:49ZengMDPI AGMetabolites2218-19892019-09-019919210.3390/metabo9090192metabo9090192Involvement of Spermidine in the Reduced Lifespan of <i>Caenorhabditis elegans</i> During Vitamin B<sub>12</sub> DeficiencyTomohiro Bito0Naho Okamoto1Kenji Otsuka2Yukinori Yabuta3Jiro Arima4Tsuyoshi Kawano5Fumio Watanabe6Department of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, JapanThe United Graduate School of Agricultural Sciences, Tottori University, Tottori 680-8553, JapanDepartment of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, JapanDepartment of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, JapanDepartment of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, JapanDepartment of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, JapanDepartment of Agricultural, Life and Environmental Sciences, Faculty of Agriculture, Tottori University, Tottori 680-8553, JapanVitamin B<sub>12</sub> deficiency leads to various symptoms such as neuropathy, growth retardation, and infertility. Vitamin B<sub>12</sub> 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<sub>12</sub> deficiency induce such symptoms. First, free amino acid levels were determined in vitamin B<sub>12</sub>-deficient <i>Caenorhabditis elegans</i> to clarify the mechanisms underlying the symptoms caused by vitamin B<sub>12</sub> deficiency. Various amino acids (valine, leucine, isoleucine, methionine, and cystathionine, among others) metabolized by vitamin B<sub>12</sub>-dependent enzymes were found to be significantly changed during conditions of B<sub>12</sub> deficiency, which indirectly affected certain amino acids metabolized by vitamin B<sub>12</sub>-independent enzymes. For example, ornithine was significantly increased during vitamin B<sub>12</sub> deficiency, which also significantly increased arginase activity. The accumulation of ornithine during vitamin B<sub>12</sub> deficiency constitutes the first report. In addition, the biosynthesis of spermidine from ornithine was significantly decreased during vitamin B<sub>12</sub> deficiency, likely due to the reduction of <i>S</i>-adenosylmethionine as a substrate for <i>S</i>-adenosylmethionine decarboxylase, which catalyzes the formation of spermidine. Moreover, vitamin B<sub>12</sub> 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<sub>12</sub>-deficient worms.https://www.mdpi.com/2218-1989/9/9/192arginase<i>Caenorhabditis elegans</i>ornithinespermidinevitamin B<sub>12</sub> |
| spellingShingle | Tomohiro Bito Naho Okamoto Kenji Otsuka Yukinori Yabuta Jiro Arima Tsuyoshi Kawano Fumio Watanabe Involvement of Spermidine in the Reduced Lifespan of <i>Caenorhabditis elegans</i> During Vitamin B<sub>12</sub> Deficiency Metabolites arginase <i>Caenorhabditis elegans</i> ornithine spermidine vitamin B<sub>12</sub> |
| title | Involvement of Spermidine in the Reduced Lifespan of <i>Caenorhabditis elegans</i> During Vitamin B<sub>12</sub> Deficiency |
| title_full | Involvement of Spermidine in the Reduced Lifespan of <i>Caenorhabditis elegans</i> During Vitamin B<sub>12</sub> Deficiency |
| title_fullStr | Involvement of Spermidine in the Reduced Lifespan of <i>Caenorhabditis elegans</i> During Vitamin B<sub>12</sub> Deficiency |
| title_full_unstemmed | Involvement of Spermidine in the Reduced Lifespan of <i>Caenorhabditis elegans</i> During Vitamin B<sub>12</sub> Deficiency |
| title_short | Involvement of Spermidine in the Reduced Lifespan of <i>Caenorhabditis elegans</i> During Vitamin B<sub>12</sub> Deficiency |
| title_sort | involvement of spermidine in the reduced lifespan of i caenorhabditis elegans i during vitamin b sub 12 sub deficiency |
| topic | arginase <i>Caenorhabditis elegans</i> ornithine spermidine vitamin B<sub>12</sub> |
| url | https://www.mdpi.com/2218-1989/9/9/192 |
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