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Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism

Cardiovascular Research Institute, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma, Omiya, Saitama-city, Saitama Prefecture 330-8503, Japan
Int. J. Mol. Sci. 2018, 19(10), 3106; https://doi.org/10.3390/ijms19103106
Received: 14 September 2018 / Revised: 1 October 2018 / Accepted: 5 October 2018 / Published: 10 October 2018
(This article belongs to the Special Issue Nutrition Genomics)
Recent investigations have revealed that changes in DNA methylation status play an important role in aging-associated pathologies and lifespan. The methylation of DNA is regulated by DNA methyltransferases (DNMT1, DNMT3a, and DNMT3b) in the presence of S-adenosylmethionine (SAM), which serves as a methyl group donor. Increased availability of SAM enhances DNMT activity, while its metabolites, S-adenosyl-l-homocysteine (SAH) and decarboxylated S-adenosylmethionine (dcSAM), act to inhibit DNMT activity. SAH, which is converted from SAM by adding a methyl group to cytosine residues in DNA, is an intermediate precursor of homocysteine. dcSAM, converted from SAM by the enzymatic activity of adenosylmethionine decarboxylase, provides an aminopropyl group to synthesize the polyamines spermine and spermidine. Increased homocysteine levels are a significant risk factor for the development of a wide range of conditions, including cardiovascular diseases. However, successful homocysteine-lowering treatment by vitamins (B6, B12, and folate) failed to improve these conditions. Long-term increased polyamine intake elevated blood spermine levels and inhibited aging-associated pathologies in mice and humans. Spermine reversed changes (increased dcSAM, decreased DNMT activity, aberrant DNA methylation, and proinflammatory status) induced by the inhibition of ornithine decarboxylase. The relation between polyamine metabolism, one-carbon metabolism, DNA methylation, and the biological mechanism of spermine-induced lifespan extension is discussed. View Full-Text
Keywords: polyamine; spermine; spermidine; methylation; DNA; lymphocyte function-associated antigen 1 (LFA-1); LFA-1 promoter (ITGAL); one carbon metabolism; DNA methyltransferases (DNMT) polyamine; spermine; spermidine; methylation; DNA; lymphocyte function-associated antigen 1 (LFA-1); LFA-1 promoter (ITGAL); one carbon metabolism; DNA methyltransferases (DNMT)
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Soda, K. Polyamine Metabolism and Gene Methylation in Conjunction with One-Carbon Metabolism. Int. J. Mol. Sci. 2018, 19, 3106.

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