Comparison of cholesterol and its direct precursors along the biosynthetic pathway: Effects of cholesterol, desmosterol and 7-dehydrocholesterol on saturated and unsaturated lipid bilayers
Bibliographic record
Abstract
Despite extensive studies, the remarkable structure-function relationship of cholesterol in cellular membranes has remained rather elusive. This is exemplified by the fact that the membrane properties of cholesterol are distinctly different from those of many other sterols. Here we elucidate this issue through atomic-scale simulations of desmosterol and 7-dehydrocholesterol (7DHC), which are immediate precursors of cholesterol in its two distinct biosynthetic pathways. While desmosterol and 7DHC differ from cholesterol only by one additional double bond, we find that their influence on saturated lipid bilayers is substantially different from cholesterol. The capability to form ordered regions in a saturated (dipalmitoyl-phosphatidylcholine) membrane is given by cholesterol > 7DHC > desmosterol, indicating the important role of cholesterol in saturated lipid environments. For comparison, in an unsaturated (dioleoyl-phosphatidylcholine) bilayer, the membrane properties of all sterols were found to be essentially identical. Our studies indicate that the different membrane ordering properties of sterols can be characterized by a single experimentally accessible parameter, the sterol tilt. The smaller the tilt, the more ordered are the lipids around a given sterol. The molecular level mechanisms responsible for tilt modulation are found to be related to changes in local packing around the additional double bonds.
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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 | 0.000 | 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 | 0.000 | 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 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".