In 1990, Dowd proposed the base strength amplification mechanism for the vitamin K-dependent ?-carboxylation of glutamate residues. Since that time, however, the strong base generated during the reaction has eluded isolation. We now suggest that the key enolate anion equivalent may be generated by means of free radical chemistry, involving the formation of a peroxy-bis-enolate that decomposes with hydrogen atom transfer from a Trp side side chain to give a triplet radical pair and a hydroxyenolate anion, which is capable of reacting with carbon dioxide to give the carboxylated product. This mechanism for the reaction also explains the effect of the W157R mutation of the carboxylase. The results of a computational study of this proposed mechanism will be presented.

Does the stroing base in the vitamin K carboxylation of Glu residues actually exist? A free radical mechanism for ?-carboxylation

246th National Meeting (2013)

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