The mechanism of action of vitamin K.
Vitamin K is the blood-clotting vitamin. The mechanism of action of vitamin K is discussed in terms of a new carbanion model that mimics the proton abstraction from the gamma position of protein-bound glutamate. This is the essential step leading to carboxylation and activation of the blood-clotting proteins. The model comprises an oxygenation that is coupled to carbon-carbon bond formation, as is the oxygenation of vitamin K hydroquinone to vitamin K oxide. The model hypothesis is also supported by the mechanism of inhibition of the carboxylase by HCN, which acts as an acid-base inhibitor rather than a metal-complexing inhibitor. The new model postulates a dioxetane intermediate that explains the presence of a second atom of 18O (from 18O2) incorporated into vitamin K oxide in the course of the enzymatic carboxylation. Finally, the chemistry developed here has been used to define the active site of vitamin K hydroquinone as the carbon-carbon bond adjacent to the methyl group.
Dowd
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Department of Chemistry, University of Pittsburgh, Pennsylvania 15260, USA.
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Naganathan
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D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D006801:Humans; D014812:Vitamin K / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology
D014812:Vitamin K; D002118:Calcium