ArticleJournal of molecular and cellular cardiology2013
Metabolic effects of glutamine on the heart: anaplerosis versus the hexosamine biosynthetic pathway.
Article in Journal of molecular and cellular cardiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 62 citations in OpenAlex.
- Pooled it
- Loss of ATP-Dependent Citrate Lyase Drives Left Ventricular Dysfunction by Metabolic Remodeling.Circulation · 2026Article
- Metabolomic and lipidomic plasma profiles according to metabolic dysfunction-associated steatotic liver diseases (MASLD) stages in the absence of type 2 diabetes (T2D).Metabolomics : Official journal of the Metabolomic Society · 2026Article
- Nuclear receptor subfamily 4 group a member 2 induces a Warburg-like effect and promotes phospholipids synthesis in the mouse heart.Physiological genomics · 2026Article
- Glutamine promotes acute wound healing by mediating glutamine metabolism and M2 macrophage polarization via the MEK/ERK/SLC1A5 signaling pathway.Scientific reports · 2026Article
- Myocardial Inflammation as Key Mediator of Heart-brain Interaction After Myocardial Ischemia/Infarction: Mechanistic Exploration of Post-Myocardial Infarction Cognitive Dysfunction.Current neuropharmacology · 2026Review
- Anaplerotic filling in heart failure: a review of mechanism and potential therapeutics.Cardiovascular research · 2024Review
- Advances in myocardial energy metabolism: metabolic remodelling in heart failure and beyond.Cardiovascular research · 2024Review
- Metabolic mechanisms in physiological and pathological cardiac hypertrophy: new paradigms and challenges.Nature reviews. Cardiology · 2023Review
- The role of glycolytic metabolic pathways in cardiovascular disease and potential therapeutic approaches.Basic research in cardiology · 2023Review
- Coordinated Metabolic Responses Facilitate Cardiac Growth in Pregnancy and Exercise.Current heart failure reports · 2023Review
- Comparative Metabolomics in Single Ventricle Patients after Fontan Palliation: A Strong Case for a Targeted Metabolic Therapy.Metabolites · 2023Review
- Metabolite signaling in the heart.Nature cardiovascular research · 2023Review
- Mechanisms shared between cancer, heart failure, and targeted anti-cancer therapies.Cardiovascular research · 2023Review
- Small molecule-mediated rapid maturation of human induced pluripotent stem cell-derived cardiomyocytes.Stem cell research & therapy · 2022Article
- Oncometabolism: A Paradigm for the Metabolic Remodeling of the Failing Heart.International journal of molecular sciences · 2022Review
- Integrated landscape of cardiac metabolism in end-stage human nonischemic dilated cardiomyopathy.Nature cardiovascular research · 2022Article
- Cardio-onco-metabolism: metabolic remodelling in cardiovascular disease and cancer.Nature reviews. Cardiology · 2022Review
- A nexus of lipid andFrontiers in endocrinology · 2022Review
- Molecular Signature of HFpEF: Systems Biology in a Cardiac-Centric Large Animal Model.JACC. Basic to translational science · 2021Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Glutamine, the most abundant amino acid in plasma, has attracted considerable interest for its cardioprotective properties. The primary effect of glutamine in the heart is commonly believed to be mediated via its anaplerotic metabolism to citric acid cycle (CAC) intermediates; however, there is little direct evidence to support this concept. Another potential candidate is the hexosamine biosynthetic pathway (HBP), which has recently been shown to modulate cardiomyocyte function and metabolism. Therefore, the goal of this study was to evaluate the contribution of anaplerosis and the HBP to the acute metabolic effects of glutamine in the heart. Normoxic ex vivo working rat hearts were perfused with (13)C-labeled substrates to assess relevant metabolic fluxes either with a physiological mixture of carbohydrates and a fatty acid (control) or under conditions of restricted pyruvate anaplerosis. Addition of a physiological concentration of glutamine (0.5mM) had no effect on contractile function of hearts perfused under the control condition, but improved that of hearts perfused under restricted pyruvate anaplerosis. Changes in CAC intermediate concentrations as well as (13)C-enrichment from [U-(13)C]glutamine did not support a major role of glutamine anaplerosis under any conditions. Under the control condition, however, glutamine significantly increased the contribution of exogenous oleate to β-oxidation, 1.6-fold, and triglyceride formation, 2.8-fold. Glutamine had no effect on malonyl-CoA or AMP kinase activity levels; however, it resulted in a higher plasma membrane level of the fatty acid transporter CD36. These metabolic effects of glutamine were reversed by azaserine, which inhibits glucose entry into the HPB. Our results reveal a metabolic role of physiological concentration of glutamine in the healthy working heart beyond anaplerosis. This role appears to involve the HBP and regulation of fatty acid entry and metabolism via CD36. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".
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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.