Regulation of 1 and 24 hydroxylation of vitamin D metabolites in the proximal tubule
Why this work is in the frame
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Bibliographic record
Abstract
Calcium and phosphate are critical for numerous physiological processes. Consequently, the plasma concentration of these ions are tightly regulated. Calcitriol, the active form of vitamin D, is a positive modulator of mineralization as well as calcium and phosphate metabolism. The molecular and physiological effects of calcitriol are well documented. Calcitriol increases blood calcium and phosphate levels by increasing absorption from the intestine, and resorption of bone. Calcitriol synthesis is a multistep process. A precursor is first made via skin exposure to UV, it is then 25-hydroxylated in the liver to form 25-hydroxyitamin D. The next hydroxylation step occurs in the renal proximal tubule via the 1-αhydroxylase enzyme (encoded by CYP27B1) thereby generating 1,25-dihydroxyvitamin D, that is, calcitriol. At the same site, the 25-hydroxyvitamin D 24-hydroxlase enzyme encoded by CYP24A1 can hydroxylate 25-hydroxyvitamin D or calcitriol to deactivate the hormone. Plasma calcitriol levels are primarily determined by the regulated expression of CYP27B1 and CYP24A1. This occurs in response to parathyroid hormone (increases CYP27B1), calcitriol itself (decreases CYP27B1 and increases CYP24A1), calcitonin (increases or decreases CYP24A1 and increases CYP27B1), FGF23 (decreases CYP27B1 and increases CYP24A1) and potentially plasma calcium and phosphate levels themselves (mixed effects). Herein, we review the regulation of CYP27B1 and CYP24A1 transcription in response to the action of classic phophocalciotropic hormones and explore the possibility of direct regulation by plasma calcium.
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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 it