Diverse biological functions of vitamin K: from coagulation to ferroptosis

Nat Metab. 2023 Jun;5(6):924-932. doi: 10.1038/s42255-023-00821-y. Epub 2023 Jun 19.

Abstract

Vitamin K is essential for several physiological processes, such as blood coagulation, in which it serves as a cofactor for the conversion of peptide-bound glutamate to γ-carboxyglutamate in vitamin K-dependent proteins. This process is driven by the vitamin K cycle facilitated by γ-carboxyglutamyl carboxylase, vitamin K epoxide reductase and ferroptosis suppressor protein-1, the latter of which was recently identified as the long-sought-after warfarin-resistant vitamin K reductase. In addition, vitamin K has carboxylation-independent functions. Akin to ubiquinone, vitamin K acts as an electron carrier for ATP production in some organisms and prevents ferroptosis, a type of cell death hallmarked by lipid peroxidation. In this Perspective, we provide an overview of the diverse functions of vitamin K in physiology and metabolism and, at the same time, offer a perspective on its role in ferroptosis together with ferroptosis suppressor protein-1. A comparison between vitamin K and ubiquinone, from an evolutionary perspective, may offer further insights into the manifold roles of vitamin K in biology.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Coagulation
  • Ferroptosis*
  • Ubiquinone
  • Vitamin K Epoxide Reductases / genetics
  • Vitamin K Epoxide Reductases / metabolism
  • Vitamin K* / metabolism

Substances

  • Vitamin K
  • Ubiquinone
  • Vitamin K Epoxide Reductases