The catalytic mechanisms of histone demethylases vary depending on the enzyme family. In the AO family, demethylation proceeds via a redox reaction where FAD is reduced and then reoxidized by molecular oxygen, producing hydrogen peroxide and demethylated histone. For the JmjC family, the mechanism involves a two-step process: first, the enzyme binds to Fe(II) and α-ketoglutarate; second, the substrate histone binds, and the methyl group is hydroxylated, forming a carbinolamine intermediate that spontaneously decomposes to release formaldehyde and the demethylated histone.
