Researchers have discovered a key component of vitamin K metabolism. The findings are reported in two papers in the 05 February 2004 issue of Nature (Vol. 427, No. 6974).
The identification of vitamin K led to the prevention of countless deaths from bleeding and blood clots, as the vitamin is a cofactor for coagulant enzymes in blood. The antagonist for these enzymes, warfarin, thins blood and is commonly used as an anticoagulant. Warfarin works by inhibiting the vitamin K epoxide reductase multiprotein complex (VKOR), a factor that is needed for blood clotting to occur. Yet the proteins involved in this process have remained elusive.
Now Johannes Oldenburg and colleagues (pp. 537-541) have identified a protein component of the VKOR complex. The team studied patients and rats with inherited defects in VKOR activity. One gene, called VKORC1, was mutated in all of the patients with warfarin resistance. The protein product of the normal gene, VKORC1, activates VKOR and is inhibited by warfarin.
Darrel W. Stafford and colleagues (pp. 541-544) identified the same key protein via a different route. Until now, researchers thought that VKOR was a large multiprotein complex. It now seems that a single protein, VKORC1, may drive its activity. "Although it seems a heavy burden for a small protein, this molecule alone may be responsible for recycling vitamin K," says J. Evan Sadler in an accompanying News and Views article.
University of Wurzburg and DRK Blood Donor Service and University of Frankfurt
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University of North Carolina at Chapel Hill
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J Evan Sadler
Washington University School of Medicine
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(C) Nature press release.
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