ArticleCell metabolism2019
Pyruvate-Carboxylase-Mediated Anaplerosis Promotes Antioxidant Capacity by Sustaining TCA Cycle and Redox Metabolism in Liver.
Article in Cell metabolism, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
135 citing papers in PubMed, 1 synthesis or guideline pooled it, 237 citations in OpenAlex.
- Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota.BMC microbiology · 2023Pooled it
- Metabolic memory in the kidney: how lactate and lactylation drive the path from acute injury to chronic disease.Renal failure · 2026Review
- Article
- Hepatic GAPDH prevents excessive fasting-induced steatosis via serine-dependent inhibition of diacylglycerol synthesis.Cell death and differentiation · 2026Article
- Loss of TCA cycle turning promotes stem cell function.bioRxiv : the preprint server for biology · 2026Article
- Vascularized Liver-on-a-Microsphere Reveals Alanine-Glucose Metabolism-Driven Regulation of Liver Function and Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Substrate supply, compartmentation, and utilization in hepatic de novo lipogenesis.Trends in endocrinology and metabolism: TEM · 2026Review
- Inhibiting pyruvate carboxylase as a potential therapeutic strategy for alleviating rheumatoid arthritis.Inflammopharmacology · 2026Article
- Proteomic and Metabolomic Profiling Reveal Mitochondrial Transplantation-Mediated Reprogramming in Gastric Cancer Cells.The Kaohsiung journal of medical sciences · 2026Article
- TCA cycle rewiring underpins histone acetylation sourcing and cell-fate transitions during exit from naive pluripotency.Cell stem cell · 2026Article
- Metabolic maintenance of breast cancer cells and metastases through E-cadherin/YAP-dependent pyruvate carboxylase expression.bioRxiv : the preprint server for biology · 2026Article
- From alpha diversity to zeitgebers: Functional implications and potential mechanisms linking the gut microbiome to sleep and circadian disruption (Part II).Neuroscience and biobehavioral reviews · 2026Review
- Loss of Propionyl-CoA Carboxylase Reprograms Hepatic Metabolism by Suppressing Mitochondrial Pyruvate Carboxylation and Fatty Acid Oxidation.bioRxiv : the preprint server for biology · 2026Article
- Pck1 Deficiency Drives Mitochondrial Dysfunction and Cellular Senescence in Adipocytes.Aging cell · 2026Article
- Distinct metabolomic and proteomic signatures in Parkinson's disease patients with REM sleep behavior disorder.Signal transduction and targeted therapy · 2026Article
- Hyperpolarized [U-ACS chemical biology · 2026Article
- vToxiNet: a biologically constrained deep learning framework for interpretable prediction of drug-induced hepatotoxicity.bioRxiv : the preprint server for biology · 2026Article
- Congenital vs adult-onset estrogen deficiency in female mice: physiological effects and implications for therapy.The Journal of endocrinology · 2026Article
- Cadmium induces ferroptosis in mouse spermatocytes by activating the ROS-TCA pathway.Scientific reports · 2026Article
- Analysis of the dynamic metabolic changes during the ripening of wolfberry (Food chemistry: X · 2026Article
75 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
Abstract
The hepatic TCA cycle supports oxidative and biosynthetic metabolism. This dual responsibility requires anaplerotic pathways, such as pyruvate carboxylase (PC), to generate TCA cycle intermediates necessary for biosynthesis without disrupting oxidative metabolism. Liver-specific PC knockout (LPCKO) mice were created to test the role of anaplerotic flux in liver metabolism. LPCKO mice have impaired hepatic anaplerosis, diminution of TCA cycle intermediates, suppressed gluconeogenesis, reduced TCA cycle flux, and a compensatory increase in ketogenesis and renal gluconeogenesis. Loss of PC depleted aspartate and compromised urea cycle function, causing elevated urea cycle intermediates and hyperammonemia. Loss of PC prevented diet-induced hyperglycemia and insulin resistance but depleted NADPH and glutathione, which exacerbated oxidative stress and correlated with elevated liver inflammation. Thus, despite catalyzing the synthesis of intermediates also produced by other anaplerotic pathways, PC is specifically necessary for maintaining oxidation, biosynthesis, and pathways distal to the TCA cycle, such as antioxidant defenses.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.