Show simple item record

dc.contributor.authorNemutlu, Emirhan
dc.contributor.authorZhang, Song
dc.contributor.authorGupta, Anu
dc.contributor.authorJuranic, Nenad O.
dc.contributor.authorMacura, Slobodan I.
dc.contributor.authorTerzic, Andre
dc.contributor.authorJahangir, Arshad
dc.contributor.authorDzeja, Petras
dc.date.accessioned2019-12-16T10:29:19Z
dc.date.available2019-12-16T10:29:19Z
dc.date.issued2012
dc.identifier.issn1094-8341
dc.identifier.urihttps://doi.org/10.1152/physiolgenomics.00152.2011
dc.identifier.urihttp://hdl.handle.net/11655/20091
dc.description.abstractNext-generation screening of disease-related metabolomic phenotypes requires monitoring of both metabolite levels and turnover rates. Stable isotope O-18-assisted P-31 nuclear magnetic resonance (NMR) and mass spectrometry uniquely allows simultaneous measurement of phosphometabolite levels and turnover rates in tissue and blood samples. The O-18 labeling procedure is based on the incorporation of one O-18 into Pi from [O-18]H2O with each act of ATP hydrolysis and the distribution of O-18-labeled phosphoryls among phosphate-carrying molecules. This enables simultaneous recording of ATP synthesis and utilization, phosphotransfer fluxes through adenylate kinase, creatine kinase, and glycolytic pathways, as well as mitochondrial substrate shuttle, urea and Krebs cycle activity, glycogen turnover, and intracellular energetic communication. Application of expanded O-18-labeling procedures has revealed significant differences in the dynamics of G-6-P[O-18] (glycolysis), G-3-P[O-18] (substrate shuttle), and G-1-P[O-18] (glycogenolysis) between human and rat atrial myocardium. In human atria, the turnover of G-3-P[O-18], which defects are associated with the sudden death syndrome, was significantly higher indicating a greater importance of substrate shuttling to mitochondria. Phosphometabolomic profiling of transgenic hearts deficient in adenylate kinase (AK1-/-), which altered levels and mutations are associated to human diseases, revealed a stress-induced shift in metabolomic profile with increased CrP[O-18] and decreased G-1-P[O-18] metabolic dynamics. The metabolomic profile of creatine kinase M-CK/ScCKmit-/--deficient hearts is characterized by a higher G-6-[O-18]P turnover rate, G-6-P levels, glycolytic capacity, gamma/beta-phosphoryl of GTP[O-18] turnover, as well as beta-[O-18]ATP and beta-[O-18]ADP turnover, indicating altered glycolytic, guanine nucleotide, and adenylate kinase metabolic flux. Thus, O-18-assisted gas chromatography-mass spectrometry and P-31 NMR provide a suitable platform for dynamic phosphometabolomic profiling of the cellular energetic system enabling prediction and diagnosis of metabolic diseases states.
dc.language.isoen
dc.publisherAmer Physiological Soc
dc.relation.isversionof10.1152/physiolgenomics.00152.2011
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCell Biology
dc.subjectGenetics & Heredity
dc.subjectPhysiology
dc.titleDynamic Phosphometabolomic Profiling of Human Tissues and Transgenic Models By O-18-Assisted P-31 Nmr and Mass Spectrometry
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/publishedVersion
dc.relation.journalPhysiological Genomics
dc.contributor.departmentAnalitik Kimya
dc.identifier.volume44
dc.identifier.issue7
dc.identifier.startpage386
dc.identifier.endpage402
dc.indexingWoS


Files in this item

This item appears in the following Collection(s)

Show simple item record