How Does Vitamin K Work in the Body?

Using a powerful microscopy technique, a team led by researchers at UT Southwestern Medical Center has gained insights into how the body uses vitamin K, an essential nutrient that plays a pivotal role in blood clotting and other physiological functions. Their findings, published in Nature, could eventually help scientists develop new anticoagulants to prevent or treat conditions including strokes, heart attacks, atrial fibrillation, and deep vein thrombosis, a type of clot that usually occurs in the legs.

“This research paves the way for innovative anticoagulation therapies by targeting the enzyme GGCX, a novel approach with the potential to overcome the limitations of current vitamin K antagonists such as warfarin,” said Xiaofeng Qi, Ph.D., Assistant Professor of Molecular Biology and member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. “This could result in safer, more effective options for patients with coagulation disorders.”

Vitamin K, which is fat-soluble and found in sources including leafy green vegetables, carrots, and organ meat, is necessary to activate a variety of proteins. These proteins are not only pivotal for clotting but also for bone and heart health, energy metabolism, brain development, and fertility, among other roles. Vitamin K activates these proteins through a chemical reaction called carboxylation, which is mediated by an enzyme called gamma-glutamyl carboxylase (GGCX). But how GGCX facilitates this reaction has been unclear.

To answer this question, Dr. Qi and his colleagues used cryo-electron microscopy (cryo-EM). By freezing molecules at temperatures around minus 196 C (about minus 320 F) and bombarding them with streams of electrons, cryo-EM produces images that can show the molecules’ three-dimensional structures at atomic resolution.

Dr. Qi’s team worked with UTSW’s Cryo-Electron Microscopy Facility to perform cryo-EM on GGCX alone, when it was bound to a vitamin K-dependent protein called osteocalcin that plays a critical role in bone metabolism, and when it was bound to both osteocalcin and vitamin K. The findings showed that GGCX had a disordered structure when it wasn't bound to other molecules. But when bound to osteocalcin, GGCX formed a pocket of the right shape and size to attach to vitamin K. The structure of GGCX bound to both osteocalcin and vitamin K confirmed that vitamin K attached to the pocket, bringing osteocalcin and vitamin K in close contact to perform carboxylation.

Surprisingly, the researchers saw another molecule in all three structures. A closer look showed that it was cholesterol, which seems to play a role in stabilizing GGCX’s structure to facilitate binding to both osteocalcin and vitamin K. This role of cholesterol in vitamin K-dependent molecular pathways was previously unknown, Dr. Qi said. Now that scientists know the structure of GGCX and how it interacts with both vitamin K and its dependent proteins, Dr. Qi added, they could design drugs that interfere with binding.

“Structure is a powerful way to reveal a molecule’s function,” Dr. Qi said. “Here, we see the structure of vitamin K and its dependent protein binding to a critical enzyme, shedding light on how the chemical reaction that activates vitamin K-dependent proteins takes place.”

Reference: Wang R, Chen B, Elghobashi-Meinhardt N, et al. Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. Nature. 2025. doi: 10.1038/s41586-024-08484-9

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