The Roles of N 6 -Methyladenosine in Human Diseases.

N  6 -Methyladenosine methylations and demethylations are associated with a number of human diseases. A chemical and biochemical perspective can complement the biological view of the epigenetic mechanism. The orbital of imino nitrogen and nitrogen-hydrogen orbital displays p-π conjugation and σ-σ hyperconjugation. The electron delocalization attenuates secondary chemical bonding, resulting in low affinities on the imino nitrogen atom to cations. Reduced proton accumulation via N  6 -methyladenosine correlates to lower cellular proton levels which may reflect cell physiology and pathogenesis. The lower affinity of the imino nitrogen to divalent cations in the methylated form versus the nonmethylated form may lead to reduced formation of insoluble and rigid calcium oxalate, which was proposed to be the cause of many diseases. The chemical and biochemical attributes of N  6 -methyladenosine crosstalk with biological pathways upregulating and/or downregulating gene expressions to give rise to various physiological and biochemical outcomes at the cellular levels and the organismal levels.