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. 2018 Oct 10;19(10):3106. doi: 10.3390/ijms19103106

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© 2018 by the author.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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The effects of decreased ODC activity and spermine supplementation. (a) Decreased ODC activity increases decarboxylated S-adenosylmethionine (dcSAM) concentrations, because the aminopropyl group from dcSAM is not required for polyamine synthesis. Increased dcSAM inhibits DNA methyltransferase (DNMT) activity, resulting in enhanced aberrant methylation of whole genome and enhanced demethylation of ITGAL (LFA-1 promoter); (b) Increased spermine from extracellular sources suppresses adenosylmethionine decarboxylase (AdoMetDC) activity due to negative feedback to maintain intracellular polyamine concentrations. Decreased dcSAM concentrations induced by decreased AdoMetDC activity results in increased DNMT activity, resulting in recovery of the ability to maintain the methylation status of the entire genome and enhancement of ITGAL methylation. T-bar indicates the inhibitory activity. Black arrow indicates the metabolic pathway or flow of substances. Brown arrow indicates the increase (upward arrow) or decrease (downward arrow) of the amount of substance or the enzymatic activity.