Possible Involvement of Hydrosulfide in B₁₂-Dependent Methyl Group Transfer

Evidence from several fields of investigation lead to the hypothesis that the sulfur atom is involved in vitamin B₁₂-dependent methyl group transfer. To compile the evidence, it is necessary to briefly review the following fields: methylation, the new field of sulfane sulfur/hydrogen sulfide (S°/H₂S), hydrosulfide derivatives of cobalamins, autoxidation of hydrosulfide radical, radical S-adenosylmethionine methyl transfer (RSMT), and methionine synthase (MS). Then, new reaction mechanisms for B₁₂-dependent methyl group transfer are proposed; the mechanisms are facile and overcome difficulties that existed in previously-accepted mechanisms. Finally, the theory is applied to the effect of S°/H₂S in nerve tissue involving the "hypomethylation theory" that was proposed 50 years ago to explain the neuropathology resulting from deficiency of vitamin B₁₂ or folic acid. The conclusions are consistent with emerging evidence that sulfane sulfur/hydrogen sulfide may be beneficial in treating Alzheimer's disease.