Ab initio molecular orbital theory is used to investigate 1,2-amino shifts catalyzed by aminomutases, coenzyme B-12, and vitamin B-6 (in the form of pyridoxal 5 ' -phosphate or PLP). Our calculations suggest essential catalytic roles for each of B-12, B-6, and the enzyme in aminomutase-catalyzed reactions. In the first place, coenzyme B-12 provides a source of abstracting radicals, allowing the rearrangement reaction to take place on the radical surface. The involvement of radicals is supported by comparison of experimental and theoretical electron paramagnetic resonance parameters. Next, B-6 allows the enzyme to lower the barrier height by introducing a double bond (allowing a low-energy intramolecular rearrangement pathway) and by providing a suitable site for partial protonation (preventing overstabilization of the reaction intermediate which could lead to enzyme inactivation). The PLP hydroxyl group is also identified as an important participant in these reactions. Finally, the enzyme holds the various reaction components in place and is the source of acidic functional groups that can provide partial protonation.