Imperial College London
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ProfessorJulianGriffin

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3220julian.griffin

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lindsay:2019:10.1007/s11306-019-1618-y,
author = {Lindsay, RT and Demetriou, D and Manetta-Jones, D and West, JA and Murray, AJ and Griffin, JL},
doi = {10.1007/s11306-019-1618-y},
journal = {Metabolomics},
title = {A model for determining cardiac mitochondrial substrate utilisation using stable 13C-labelled metabolites},
url = {http://dx.doi.org/10.1007/s11306-019-1618-y},
volume = {15},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - INTRODUCTION: Relative oxidation of different metabolic substrates in the heart varies both physiologically and pathologically, in order to meet metabolic demands under different circumstances. 13C labelled substrates have become a key tool for studying substrate use-yet an accurate model is required to analyse the complex data produced as these substrates become incorporated into the Krebs cycle. OBJECTIVES: We aimed to generate a network model for the quantitative analysis of Krebs cycle intermediate isotopologue distributions measured by mass spectrometry, to determine the 13C labelled proportion of acetyl-CoA entering the Krebs cycle. METHODS: A model was generated, and validated ex vivo using isotopic distributions measured from isolated hearts perfused with buffer containing 11 mM glucose in total, with varying fractions of universally labelled with 13C. The model was then employed to determine the relative oxidation of glucose and triacylglycerol by hearts perfused with 11 mM glucose and 0.4 mM equivalent Intralipid (a triacylglycerol mixture). RESULTS: The contribution of glucose to Krebs cycle oxidation was measured to be 79.1 ± 0.9%, independent of the fraction of buffer glucose which was U-13C labelled, or of which Krebs cycle intermediate was assessed. In the presence of Intralipid, glucose and triglyceride were determined to contribute 58 ± 3.6% and 35.6 ± 0.8% of acetyl-CoA entering the Krebs cycle, respectively. CONCLUSION: These results demonstrate the accuracy of a functional model of Krebs cycle metabolism, which can allow quantitative determination of the effects of therapeutics and pathology on cardiac substrate metabolism.
AU  - Lindsay,RT
AU  - Demetriou,D
AU  - Manetta-Jones,D
AU  - West,JA
AU  - Murray,AJ
AU  - Griffin,JL
DO  - 10.1007/s11306-019-1618-y
PY  - 2019///
SN  - 1573-3882
TI  - A model for determining cardiac mitochondrial substrate utilisation using stable 13C-labelled metabolites
T2  - Metabolomics
UR  - http://dx.doi.org/10.1007/s11306-019-1618-y
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31773381
UR  - http://hdl.handle.net/10044/1/81852
VL  - 15
ER  -
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