ArticleNature chemical biology2016
Malic enzyme tracers reveal hypoxia-induced switch in adipocyte NADPH pathway usage.
Article in Nature chemical biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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
76 citing papers in PubMed.
- TCA cycle rewiring underpins histone acetylation sourcing and cell-fate transitions during exit from naive pluripotency.Cell stem cell · 2026Article
- Insights into Neutrophil Dysfunction in Inherited Metabolic Disorders.Journal of innate immunity · 2026Review
- Oxidative pentose phosphate pathway is required for T cell activation and antitumor immunity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Keeping up with the nicotinamides: NADP(H), the forgotten circadian cofactor that keeps metabolic time.Life metabolism · 2025Review
- The integral membrane protein smim4 modulates redox balance via malate compartmentalization in pancreatic cancer.Nature communications · 2025Article
- Cold-inducible GOT1 activates the malate-aspartate shuttle in brown adipose tissue to support fuel preference for fatty acids.Cell reports · 2025Article
- Overfeeding induces adipose tissue release of distinct mitochondria.Cell reports · 2025Article
- The Role of Reductive Stress in the Pathogenesis of Endocrine-Related Metabolic Diseases and Cancer.International journal of molecular sciences · 2025Review
- In defence of ferroptosis.Signal transduction and targeted therapy · 2025Review
- NADPCurrent medicinal chemistry · 2025Review
- Malic enzymes in cancer: Regulatory mechanisms, functions, and therapeutic implications.Redox biology · 2024Review
- The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity.Antioxidants (Basel, Switzerland) · 2024Review
- Isocitrate Dehydrogenase Mutations in Cancer: Mechanisms of Transformation and Metabolic Liability.Cold Spring Harbor perspectives in medicine · 2024Review
- AKT1 phosphorylation of cytoplasmic ME2 induces a metabolic switch to glycolysis for tumorigenesis.Nature communications · 2024Article
- The pentose phosphate pathway in health and disease.Nature metabolism · 2023Review
- Article
- Cytosolic and mitochondrial NADPH fluxes are independently regulated.Nature chemical biology · 2023Article
- Cellular redox homeostasis maintained by malic enzyme 2 is essential for MYC-driven T cell lymphomagenesis.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Regulation at Drosophila's Malic Enzyme highlights the complexity of transvection and its sensitivity to genetic background.Genetics · 2023Article
- IDH2, a novel target of OGT, facilitates glucose uptake and cellular bioenergy production via NF-κB signaling to promote colorectal cancer progression.Cellular oncology (Dordrecht, Netherlands) · 2023Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors.
Funding
Abstract
The critical cellular hydride donor NADPH is produced through various means, including the oxidative pentose phosphate pathway (oxPPP), folate metabolism and malic enzyme. In growing cells, it is efficient to produce NADPH via the oxPPP and folate metabolism, which also make nucleotide precursors. In nonproliferating adipocytes, a metabolic cycle involving malic enzyme holds the potential to make both NADPH and two-carbon units for fat synthesis. Recently developed deuterium ((2)H) tracer methods have enabled direct measurement of NADPH production by the oxPPP and folate metabolism. Here we enable tracking of NADPH production by malic enzyme with [2,2,3,3-(2)H]dimethyl-succinate and [4-(2)H]glucose. Using these tracers, we show that most NADPH in differentiating 3T3-L1 mouse adipocytes is made by malic enzyme. The associated metabolic cycle is disrupted by hypoxia, which switches the main adipocyte NADPH source to the oxPPP. Thus, (2)H-labeled tracers enable dissection of NADPH production routes across cell types and environmental conditions.
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.