The CoQ biosynthetic di-iron carboxylate hydroxylase COQ7 is inhibited by in vivo metalation with manganese but remains function by metalation with cobalt
Bibliographic record
Abstract
ABSTRACT COQ7 is a mitochondrial hydroxylase that catalyzes the penultimate step of the biosynthesis of coenzyme Q (CoQ; ubiquinone). CoQ is an obligate component of the mitochondrial electron transport chain and an antioxidant. CoQ deficiencies due to mutations in CoQ biosynthetic enzymes are severe genetic disorders often manifesting as mitochondrial disease syndrome. COQ7 is part of the relatively rare class of di-iron carboxylate enzymes, which carry out a wide range of reactions. In a previous study we described how COQ7 activity is inhibited in mammalian cells after treatment with iron chelating agents. Here, we report that manganese exposure of mouse cells leads to decreased COQ7 activity and resulting CoQ deficiency, which might participate in manganese toxicity. We find that the presence of cobalt can interfere with the inhibition of COQ7 by manganese. We present evidence that both manganese inhibition and cobalt interference are the result of metal exchange at the di-iron active site of COQ7. We present findings that suggest that 1) cobalt has greater affinity for the active site of COQ7 than both iron and manganese and, 2) that iron replacement by cobalt at the active site preserves catalytic activity.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".