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Studies of vitamin K-dependent carboxylase

Thesis/Dissertation ·
OSTI ID:5281553

Carboxylase was studied in detergent solubilized rat liver microsomes, using the peptide substrate Phe-Leu-(..gamma..-/sup 3/H)-Glu-Glu-Leu. Cleavage of the ..gamma..-C-H bond in Glu was measured as the release of /sup 3/H from this peptide to water, carboxylation was measured as the incorporation of H/sup 14/CO/sub 3/-into the peptide, and KO formation was measured by an HPLC assay. All three products could be measured simultaneously, and this system was used to examine the effects of cyanide, manganese, tetrachloropyridinol, and Boc-SerP-SerP-Leu-OMe on the separate steps of the carboxylase reaction. Vitamin K-epoxide formation was studied separately from the other reactions, and it was found that in the absence of a Glu-containing substrate, carboxylase catalyzed the uncoupled formation of KO from KH/sub 2/ and O/sub 2/. The stoichiometry of product formation (GLa, KO, and ..gamma..-protons) was measured, and the results obtained were all in agreement with the values predicted from the proposed mechanism. When all of the substrates were saturating, the stoichiometry of ..gamma..-C-H bond cleavage, carboxylation, and KO formation was 1:1:1.

Research Organization:
Wisconsin Univ., Madison (USA)
OSTI ID:
5281553
Country of Publication:
United States
Language:
English