Summary of Study ST000451

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR000349. The data can be accessed directly via it's Project DOI: 10.21228/M8XS4Q This work is supported by NIH grant, U2C- DK119886.


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Study IDST000451
Study TitleThe alpha-1A adrenergic receptor agonist A61603 reduces cardiac polyunsaturated fatty acid-Heart raw data
Study TypeGC-MS non-targeted metabolomic profiling
Study SummaryStudies of skeletal muscle disuse either in patients on bed rest or experimentally in animals(immobilization) have demonstrated that decreased protein synthesis is common, with transient parallel increases in protein degradation. Muscle disuse atrophy involves a process of transition from slow to fast myosin fiber types 6 . A shift toward glycolysis, decreased capacity for fat oxidation, and substrate accumulation in atrophied muscles have been reported as has accommodation of the liver with an increased gluconeogenic capacity. Recent studies have modeled skeletal muscle disuse by using cyclic stretch of differentiated myotubes (C2C12), which mimics the loading pattern of mature skeletal muscle, followed by cessation of stretch.We utilized this model to determine the metabolic changes using non-targeted metabolomics analysis of the media. We identified increases in amino acids resulting from protein degradation (largely sarcomere) that occurs with muscle atrophy that are involved in feeding the Kreb’s cycle through anaplerosis. Specifically, we identified increased alanine/proline metabolism (significantly elevated proline, alanine, glutamine, and asparagine) and increased -ketoglutaric acid, the proposed Kreb’s cycle intermediate being fed by the alanine/proline metabolic anaplerotic mechanism. Additionally, several unique pathways not clearly delineated in previous studies of muscle unloading were seen, including: 1) elevated ethanolamine and elevated keto-acids (e.g. 2-ketoleucine and 2-keovaline) represent intermediates in the Ehlrich amino acid degradation pathway, which feeds into a metabolic pathway supplying acetyl-CoA and 2-hydroxybutyrate (also significantly increased); and 2) elevated guanine, an intermediate of purine metabolism, was seen at 12 hours unloading. Given the interest in targeting different aspects of the ubiquitin proteasome system to inhibit protein degradation, this C2C12 system may allow the identification of direct and indirect alterations in metabolism due to anaplerosis or through other yet to be identified mechanisms using a non-targeted metabolomics approach.
University of North Carolina at Chapel Hill
DepartmentMcAllister Heart Institute
LaboratoryMutliple Centers
Last NameIlaiwy;WIllis
First NameAmro;Monte
Address111 Mason Farm road, Chapel Hill, North Carolina, 27599-7126, USA,
Submit Date2016-08-17
Analysis Type DetailGC-MS
Release Date2016-09-23
Release Version1
Amro Ilaiwy Amro Ilaiwy
Monte WIllis Monte WIllis application/zip

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Combined analysis:

Analysis ID AN000707
Analysis type MS
Chromatography type GC
Chromatography system Waters Acquity
Column Waters Acquity BEH C18 (100 x 2mm,1.7um)
MS Type EI
MS instrument type Single quadrupole
MS instrument name Agilent 5975
Units Peak values (scaled)


Chromatography ID:CH000511
Instrument Name:Waters Acquity
Column Name:Waters Acquity BEH C18 (100 x 2mm,1.7um)
Chromatography Type:GC