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

PubMed ID: 290992

Author(s): Friedman PA, Shia MA, Gallop PM, Griep AE. Vitamin K-dependent gamma-carbon-hydrogen bond cleavage and nonmandatory concurrent carboxylation of peptide-bound glutamic acid residues. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3126-9. PMID 290992

Journal: Proceedings Of The National Academy Of Sciences Of The United States Of America, Volume 76, Issue 7, Jul 1979

The pentapeptide Phe-Leu-Glu-Glu-Leu, tritiated at the gamma carbon of each Glu residue, has been 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 in which 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. However, two carboxylation mechanisms compatible with the results are discussed.