Journal
ANNUAL REVIEW OF NUTRITION, VOL 38
Volume 38, Issue -, Pages 127-151Publisher
ANNUAL REVIEWS
DOI: 10.1146/annurev-nutr-082117-051741
Keywords
vitamin K; Gla proteins; vitamin K cycle; intestinal absorption; intermediary metabolism; UBIAD1
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Vitamin K (VK) is an essential cofactor for the post-translational conversion of peptide-bound glutamate to gamma-carboxyglutamate. The resultant vitamin K-dependent proteins are known or postulated to possess a variety of biological functions, chiefly in the maintenance of hemostasis. The vitamin K cycle is a cellular pathway that drives gamma-carboxylation and recycling of VK via gamma-carboxyglutamyl carboxylase (GGCX) and vitamin K epoxide reductase (VKOR), respectively. In this review, we show how novel molecular biological approaches are providing new insights into the pathophysiological mechanisms caused by rare mutations of both GGCX and VKOR. We also discuss how other protein regulators influence the intermediary metabolism of VK, first through intestinal absorption and second through a pathway that converts some dietary phylloquinone to menadione, which is prenylated to menaquinone-4 (MK-4) in target tissues by UBIAD1. The contribution of MK-4 synthesis to VK functions is yet to be revealed.
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