By Gerald Litwack
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Additional info for Vitamin K
Conclusion The description of the VKORC1 gene, in 2004, provided an important step forward in understanding vitamin K metabolism. In the first place, this discovery is giving us detailed insight in the biochemical pathway involved in vitamin K cycling, including the putative role of PDI. In addition, the discovery of the VKORC1 gene was important for understanding the wide variability in the individual response to vitamin K antagonists like warfarin. Several studies have shown that the activity of the VKORC1 enzyme is determined by genetic variants, which helps to explain interindividual and also interethnic differences in therapeutic response to coumarin drugs.
However, there was considerable evidence against this hypothesis. , 1999). Also, it has been shown that calumenin, a member of the CREC (Cab-45, reticulocalbin, ERK-45, and calumenin) subfamily of Ca2þ-binding proteins, inhibits VKOR activity and confers warfarin resistance to VKOR in COS-1 cells (Wallin and Hutson, 2004). , 2004b). Nevertheless, because the active site of VKOR appears to include a canonical CIVC redox motif, one would expect that another enzyme is participating in the reaction.
2001). Role of K vitamins in the regulation of tissue calcification. J. Bone Miner. Metab. 19, 201–206. , et al. (2006). VKORC1 haplotypes are associated with arterial vascular diseases (stroke, coronary heart disease, and aortic dissection). Circulation 113, 1615–1621. Weintraub, M. , and Breslow, J. L. (1987). Dietary fat clearance in normal subjects is regulated by genetic variation in apolipoprotein E. J. Clin. Invest. 80, 1571–1577. , and Prentice, A. (2004). Vitamin K status of older individuals in northern China is superior to that of older individuals in the UK.