Comprehensive quantification of fuel use by the failing and nonfailing human heart
Danielle Murashige,Cholsoon Jang,Michael D. Neinast,Jonathan J. Edwards,Alexis J. Cowan,Matthew C. Hyman,Joshua D. Rabinowitz,David S. Frankel,Zolt Arany +8 more
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TLDR
A comprehensive and quantitative picture of human cardiac fuel use is provided, using blood from artery, coronary sinus, and femoral vein in 110 patients with or without heart failure to quantify the uptake and release of 277 metabolites.Abstract:
The heart consumes circulating nutrients to fuel lifelong contraction, but a comprehensive mapping of human cardiac fuel use is lacking. We used metabolomics on blood from artery, coronary sinus, and femoral vein in 110 patients with or without heart failure to quantify the uptake and release of 277 metabolites, including all major nutrients, by the human heart and leg. The heart primarily consumed fatty acids and, unexpectedly, little glucose; secreted glutamine and other nitrogen-rich amino acids, indicating active protein breakdown, at a rate ~10 times that of the leg; and released intermediates of the tricarboxylic acid cycle, balancing anaplerosis from amino acid breakdown. Both heart and leg consumed ketones, glutamate, and acetate in direct proportionality to circulating levels, indicating that availability is a key driver for consumption of these substrates. The failing heart consumed more ketones and lactate and had higher rates of proteolysis. These data provide a comprehensive and quantitative picture of human cardiac fuel use.read more
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Myocardial Metabolomics of Human Heart Failure With Preserved Ejection Fraction
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A mitochondrial long-chain fatty acid oxidation defect leads to tRNA uncharging and activation of the integrated stress response in the mouse heart.
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Ketones and the Heart: Metabolic Principles and Therapeutic Implications
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References
More filters
Journal ArticleDOI
DrugBank 5.0: a major update to the DrugBank database for 2018
David S. Wishart,Yannick Djoumbou Feunang,An Chi Guo,Elvis J. Lo,Ana Marcu,Jason R. Grant,Tanvir Sajed,Daniel Johnson,Carin Li,Zinat Sayeeda,Nazanin Assempour,Ithayavani Iynkkaran,Yifeng Liu,Adam Maciejewski,Nicola Gale,Alex Wilson,Lucy Chin,Ryan Cummings,Diana Le,Allison Pon,Craig Knox,Michael Wilson +21 more
TL;DR: This year’s update, DrugBank 5.0, represents the most significant upgrade to the database in more than 10 years and significant improvements have been made to the quantity, quality and consistency of drug indications, drug binding data as well as drug-drug and drug-food interactions.
Journal ArticleDOI
HMDB 4.0: the human metabolome database for 2018.
David S. Wishart,Yannick Djoumbou Feunang,Ana Marcu,An Chi Guo,Kevin Y. H. Liang,Rosa Vázquez-Fresno,Tanvir Sajed,Daniel Johnson,Carin Li,Naama Karu,Zinat Sayeeda,Elvis J. Lo,Nazanin Assempour,Mark V. Berjanskii,Sandeep Singhal,David Arndt,Yongjie Liang,Hasan Badran,Jason R. Grant,Arnau Serra-Cayuela,Yifeng Liu,Rupa Mandal,Vanessa Neveu,Allison Pon,Craig Knox,Michael Wilson,Claudine Manach,Augustin Scalbert +27 more
TL;DR: This year's update to the HMDB, HMDB 4.0, represents the most significant upgrade to the database in its history and should greatly enhance its ease of use and its potential applications in nutrition, biochemistry, clinical chemistry, clinical genetics, medicine, and metabolomics science.
Journal ArticleDOI
The failing heart--an engine out of fuel.
TL;DR: This review describes cardiac energy metabolism, appraises the methods used for its assessment, evaluates the role of impaired energy metabolism in heart failure, and gives options for metabolic therapy.
Journal ArticleDOI
Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Cosimo Commisso,Shawn M. Davidson,Rengin G. Soydaner-Azeloglu,Seth J. Parker,Jurre J. Kamphorst,Sean R. Hackett,Elda Grabocka,Michel Nofal,Jeffrey A. Drebin,Craig B. Thompson,Joshua D. Rabinowitz,Christian M. Metallo,Matthew G. Vander Heiden,Matthew G. Vander Heiden,Dafna Bar-Sagi +14 more
TL;DR: In this paper, it was shown that Ras-transformed cells use macropinocytosis to transport extracellular protein into the cell, yielding amino acids including glutamine that can enter central carbon metabolism.
Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Cosimo Commisso,Shawn M. Davidson,Rengin G. Soydaner-Azeloglu,Seth J. Parker,Jurre J. Kamphorst,Sean R. Hackett,Elda Grabocka,Michel Nofal,Jeffrey A. Drebin,Craig B. Thompson,Joshua D. Rabinowitz,Christian M. Metallo,Matthew G. Vander Heiden,Matthew G. Vander Heiden,Dafna Bar-Sagi +14 more
TL;DR: It is shown that Ras-transformed cells use macropinocytosis to transport extracellular protein into the cell, and its pharmacological inhibition compromises the growth of Ras- transformed pancreatic tumour xenografts.
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