Phosphatidylethanolamine‐methylation is an important consumer of methyl groups in mice and humans
Bibliographic record
Abstract
Biological methylation reactions and homocysteine (Hcy) metabolism are intimately linked. Phosphatidylethanolamine N ‐methyltransferase (PEMT) is an enzyme of phosphatidylcholine (PC) synthesis that is localized predominantly in liver. It catalyses the synthesis of PC from PE, consuming 3 AdoMet molecules in three successive methylations. We hypothesized that the PEMT reaction might contribute significantly to plasma Hcy. Our data show that Pemt −/− mice have plasma Hcy levels ~50% of those in wild type mice. Hepatocytes isolated from Pemt −/− mice secrete ~50% less Hcy. Mice that lack hepatic CTα, however, have significantly elevated plasma Hcy since CTα‐deficient hepatocytes secreted more Hcy than control cells. These data suggest that phospholipid methylation in the liver is a major consumer of AdoMet and a significant source of plasma Hcy. However, our mice data is not consistent early studies in humans which suggest that creatine synthesis accounts for utilization of more than 70% of AdoMet‐derived methyl groups. A re‐examination of human creatine metabolism reveals that, in non‐vegetarians, dietary creatine can account for as much as 50% of daily creatine requirements and, therefore, that estimates of creatine synthesis need to be reduced. We suggest that creatine synthesis is responsible for a much smaller proportion of AdoMet‐derived methyl groups than has been suggested and that phosphatidylcholine synthesis via PEMT is a major consumer of these methyl groups.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".