Overexpression of protein disulfide isomerase enhances vitamin K epoxide reductase activity
Bibliographic record
Abstract
Vitamin K epoxide reductase (VKOR) activity is catalyzed by the VKORC1 enzyme. It is a target of vitamin K antagonists (VKA). Numerous mutations of VKORC1 have been reported and are suspected to confer resistance to VKA and (or) affect its velocity. Nevertheless, the results of these studies have been conflicting, and the functional characterization of these mutations in the cell system is complex because of the interweaving of VKOR activity in the vitamin K cycle. In this study, a new cellular approach was implemented to evaluate the vitamin K cycle in HEK293 cells. This global approach was based on the vitamin K quinone/vitamin K epoxide (K/KO) balance. In the presence of VKA or when VKORC1 and VKORC1L1 were knocked out, the K/KO balance decreased significantly due to the accumulation of vitamin KO. In contrast, when VKORC1 was overexpressed, the balance remained unchanged, demonstrating the limitation of VKOR activity. This limitation was shown to be due to insufficient expression of the activation partner of VKORC1, as overexpression of protein disulfide isomerase (PDI) overcomes this limitation. This study is the first to demonstrate the functional interaction between VKORC1 and PDI.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".