Post-translational carboxylation of preprothrombin

Summary In summary, in this review on the function of vitamin K in post-translational modification of precursor proteins by carboxylation of certain glutamyl residues, I have tried to cover in particular the recent work on the reaction, the enzymes involved and the mechanisms being considered.In doing this I have also considered vitamin K, its discovery, its functional form and the possible relation of its metabolism to the carboxylation reaction. Equally the various vitamin K-dependent gla-containing proteins currently known have been described. The carboxylation of synthetic small molecule exogenous substrates and the synthesis and metabolism of the products of carboxylation are of great help in studying the reaction.Structural specificity of vitamin K analogs in vivo and in vitro has been compared and the use of various antagonists in vivo and in vitro considered in attempts to gain an understanding of the overall reaction.The reactions subsequent to carboxylation, e.g., the activation of prothrombin to thrombin via serine proteases and the related activation of the other vitamin K-dependent proteins have not been considered in this review. The review has not covered prothrombin or other vitamin K-dependent protein isolation, nor the determination of these proteins.As the vitamin K-dependent protein carboxylation story has developed over the past six years, a number of reviews have been written which help in keeping up with the various aspects of the field as it has expanded. These reviews refer to many of the papers I have had to eliminate due to space limitations. They are referenced as 469–489.The review is in no sense comprehensive and many papers have been missed or only mentioned. I have tried to concentrate on the more recent work and, thus, much of the very fine work of the 1940's on vitamin K chemistry is hardly mentioned.Some redundancy has been built into the organization of the review so that a reader can obtain a reasonable view of any one section without having to search the whole review for all possible relevant information on any particular part of the field.