In the reaction cycle of glutamate carboxylase, vitamin K epoxidation by O-2 has been proposed to generate a very strong base able to remove a proton from the gamma carbon of a Glu residue, thus yielding a Glu-based carbanion that readily reacts with CO2. We have used hybrid density functional theory to study this appealing mechanism. Our calculations show a very exergonic four-step mechanism with the reaction of (triplet) O-2 with the singlet vitamin K anion as the rate-limiting step, with a rate similar to the experimental value. Our study also establishes the need to apply continuum models when performing the optimization of minimum-energy crossing points between potential energy surfaces of different multiplicities for enzyme model systems.