Relationship between polyamine metabolism and methylation. Increased dcSAM has been shown to inhibit Dnmt activity.

<p>The polyamines spermine and spermidine are synthesized from arginine and SAM. Inhibition of polyamine synthesis by DFMO increases dcSAM relative to SAM. Increased spermine from extracellular sources decreases conversion from SAM to dcSAM. Similarly, MGBG inhibits AdoMetDC activities, resulting in increased SAM and decreased dcSAM. SAM: S-adenosylmethionine, DFMO: D,L-alpha-difluoromethylornithine hydrochloride, dcSAM: decarboxylated S-adenosylmethionine, MGBG: methylglyoxal bis-guanylhydrazone, AdoMetDC: S-adenosyl-L-methionine-decarboxylase, ODC: ornithine decarboxylase. Dnmt: DNA methyltransferase.