Vitamin K-dependent carboxylase. Possible role for thioredoxin in the reduction of vitamin K metabolites in liver.
In the liver vitamin K epoxide, which is produced during the posttranslational carboxylation of protein-bound glutamic acid residues, is recycled by the action of one or more dithiol-dependent reductases. In vitro synthetic dithiols may serve as a cofactor for these enzymes, but the physiological reductant has not yet been found. In this paper we report that in vitro the commercially available thioredoxin/thioredoxin reductase from E. coli can replace the synthetic dithiols during the various reactions of the vitamin K cycle. Based on the assumption that in vivo thioredoxin also plays a role in the regeneration of vitamin K hydroquinone from the epoxide, an extension of the generally accepted vitamin K cycle is proposed.
Johan
L
L
Department of Biochemistry, University of Limburg, Maastricht, The Netherlands.
van Haarlem
M
M
Soute
B A
BA
Vermeer
C
C
D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D019735:Carbon-Carbon Ligases; D002417:Cattle; D004926:Escherichia coli / Q000201:enzymology; D008025:Ligases / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism; D013879:Thioredoxins / Q000494:pharmacology*; D014812:Vitamin K / Q000378:metabolism*
D001426:Bacterial Proteins; D014812:Vitamin K; D013879:Thioredoxins; D013880:Thioredoxin-Disulfide Reductase; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase