The VK cycle in which GGCX adds a carboxylic acid to specific Glu residues in VKD proteins, thereby using VK hydroquinone as cosubstrate. VKOR reduces the generated KO to VK, which is further reduced by VKOR and VKR. Monitoring reporter protein γ-carboxylation in GGCX or VKOR (DGKO) knockout cell lines using KO as substrate and quantifying KO/VK formation via high-performance liquid chromatography (HPLC) analysis led to the identification of drugs that inhibited VKOR, VKR, or intracellular VK availability. With regard to the last, small amounts of intracellular VK precluded accurate KO/VK assessment for 1 drug (“Not determined”). The figure has been adapted from Figure 1A in the article by Chen et al that begins on page 898.

The VK cycle in which GGCX adds a carboxylic acid to specific Glu residues in VKD proteins, thereby using VK hydroquinone as cosubstrate. VKOR reduces the generated KO to VK, which is further reduced by VKOR and VKR. Monitoring reporter protein γ-carboxylation in GGCX or VKOR (DGKO) knockout cell lines using KO as substrate and quantifying KO/VK formation via high-performance liquid chromatography (HPLC) analysis led to the identification of drugs that inhibited VKOR, VKR, or intracellular VK availability. With regard to the last, small amounts of intracellular VK precluded accurate KO/VK assessment for 1 drug (“Not determined”). The figure has been adapted from Figure 1A in the article by Chen et al that begins on page 898.

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