Vitamin K-dependent gamma-carbon-hydrogen bond cleavage and nonmandatory concurrent carboxylation of peptide-bound glutamic acid residues.

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Abstract
The pentapeptide Phe-Leu-Glu-Glu-Leu, tritiated at the .gamma. carbon of each Glu residue, was synthesized. In a system using microsomal preparations derived from rat liver, vitamin K-dependent tritium release from the L-Glu residues of this substrate can occur without the concurrent .gamma.-carboxylation of Glu. This tritium release reaction, which indicates cleavage of the .gamma.C-H bond, although easily uncoupled from CO2-dependent .gamma.C carboxylation, does require the reduced (hydroquinone) form of vitamin K and oxygen. The data argue against a concerted mechanism for the cleavage of the .gamma.C-H bond and carboxylation and against a mechanism where the vitamin functions solely to transfer or activate CO2. Although the tritium release is related clearly to the oxidation of vitamin KH2, it is not yet established how the subsequent carboxylation proceeds. Two carboxylation mechanisms compatible with the results are discussed.