Figure 3.

The methionine cycle and alternative homocysteine degradation regulate DNMT and HMT activity. HMT and DMMT catalyze histone and DNA methylation, respectively. The donor of the methyl group is the metabolite S-adenosylmethionine (SAM) which is then converted into S-adenosylhomocysteine (SAH). SAH is regenerated into SAM during the methionine cycle (red lines) where the loss of adenosine induces its transformation into homocysteine. The methyl group of 5-Methyltetrahydrofolate (5-MethylTHF) from the folate cycle (orange lines) is then transferred to homocysteine to form methionine. Depending of the metabolic needs, homocysteine can be catabolized into sulfate, taurine or cysteine. This alternative pathway is represented by dotted lines. The regeneration of SAH into SAM is then compromised and negatively impacts HMT and DNMT activity. Created with BioRender.com.