Photolysis and Recombination of Adenosylcobalamin Bound to Glutamate Mutase

摘要

Adenosylcobalamin-dependent (coenzyme B_(12), AdoCbl) enzymes catalyze a variety of chemically difficult reactions that proceed by mechanisms involving organic radicals. Radicals are initially generated by fission of the coenzyme cobalt-carbon bond to generate adenosyl radical and cob(II)alamin. In free solution at room temperature, the bond dissociation energy of the Co-C bond is 32 kcal/mol and the half-time for homolysis is estimated to be about 6 months. In contrast, when bound to an enzyme, homolysis occurs on the millisecond time scale in response to substrate binding, and the internal equilibrium constant for homolysis is close to one. The unusual nature of the homolysis reaction has prompted numerous investigations on model compounds, coenzyme analogues, and the enzymes themselves, aimed at understanding how the enzymes achieve the ～10~(12)-fold acceleration in the rate of AdoCbl homolysis. However, this aspect of catalysis remains poorly understood.