The key step in the catalytic cycle of methionine symhase (MetH) is the transfer of a methyl group from the methylcobalamin (MeCb1) cofactor to homocysteine (I Icy). This mechanism has been traditionally viewed as an SN2-type reaction, but a different mechanism based on one-electron reduction of the cofactor (reductive cleavage) has been recently proposed. In this work, we analyze whether this mechanism is plausible from a theoretical point of view. By means of a combination of gas-phase as well as hybrid QM/MM calculations, we show that cleavage of the Co-C bond in a MeCbl center dot center dot center dot Hey complex (1-Icy = methylthiolate substrate (Me-S-), a structural mimic of deprotonated hornocysteine) proceeds via a [Co-III(corrin-)]-Me center dot center dot center dot S-center dot-Me diradical configuration, involving electron transfer (ET) from a pi*(corrin)-type state to a sigma*(co-c) one, and the methyl transfer displays an energy barrier <= 8.5 kcal/mol. This value is comparable to the one previously computed for the alternative S(N)2 reaction pathway (10.5 kcal/mol). However, the ET-based reductive cleavage pathway does not impose specific geometrical and distance constraints with respect to substrate and cofactor. as does the SN2 pathway. This might be advantageous from the enzymatic point of view because in that case. a methyl croup can be transferred efficiently at longer distances.