The stereochemistry of hydrogen abstraction in vitamin K-dependent carboxylation.
The stereochemistry of the hydrogen abstraction in the vitamin K-dependent carboxylation of synthetic peptides has been investigated; the carboxylation rates of various peptidic substrates containing a stereospecifically 4-monodeuterated glutamic acid residue have been compared to that of nondeuterated peptides. A significant isotope effect was found only with the substrates containing (4S)-4-deuterated glutamic acid. These data reveal that the rat liver microsomal vitamin K-dependent carboxylase acts stereospecifically in abstracting the 4-pro-S hydrogen of the glutamyl residue. The low values of the measured isotope effects indicate that the hydrogen abstraction does not constitute a limiting step in the carboxylation mechanism.
D000818:Animals; D002245:Carbon Dioxide / Q000378:metabolism; D002250:Carbon Radioisotopes; D055598:Chemical Phenomena; D002621:Chemistry; D003903:Deuterium; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D006859:Hydrogen; D007700:Kinetics; D008862:Microsomes, Liver / Q000378:metabolism*; D009842:Oligopeptides / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D014812:Vitamin K / Q000378:metabolism*; D014813:Vitamin K Deficiency / Q000378:metabolism
D002250:Carbon Radioisotopes; D005971:Glutamates; D009842:Oligopeptides; D014812:Vitamin K; D002245:Carbon Dioxide; D018698:Glutamic Acid; D006859:Hydrogen; D003903:Deuterium