Inhibition of hepatic phosphatidylcholine synthesis by AICAR and phenformin is independent of AMP‐activated protein kinase (AMPK) activation.
Bibliographic record
Abstract
Hepatocytes can synthesize phosphatidylcholine (PC) via two pathways; the CDP‐choline pathway, is expressed in all cells and requires dietary choline. In the second (liver‐specific) pathway, phosphatidylethanolamine is methylated to phosphatidylcholine via the enzyme phosphatidylethanolamine N‐methyltransferase (PEMT). The present study investigated whether AMPK regulates phosphatidylcholine biosynthesis in hepatocytes. Chemical activator of AMPK (phenformin and AICAR) inhibited both PC biosynthetic pathways in isolated hepatocytes, suggesting AMPK plays an important role in regulating phospholipid metabolism. However, when isolated hepatocytes were infected with a recombinant adenovirus expressing a constitutively active form of AMPK, there was no change in the rate of phosphatidycholine formation. Furthermore, adenovirus expression of a dominant‐negative mutant of AMPK did not block the effects of phenformin and AICAR. By measuring enzyme activities and pathway intermediates we were able to show that phenformin and AICAR have different sites of action. For example, phenformin directly inhibits in vitro PEMT activity while AICAR does not. It appears that AICAR may inhibit PEMT‐flux by increasing the intracellular concentration of S‐adenosylhomocysteine, a potent inhibitor of methylation reactions. AICAR seems to inhibit the CDP‐choline pathway by increasing choline oxidation while phenformin seems in impair choline uptake into the cell. Taken together, this study indicates that AICAR and phenformin are potent inhibitors of hepatic PC biosynthesis however these affects are independent of AMPK action.
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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 | 0.000 | 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) | 0.001 | 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".