Advanced

Tissue-specific short chain fatty acid metabolism and slow metabolic recovery after ischemia from hyperpolarized NMR in vivo

Jensen, Pernille R; Peitersen, Torben; Karlsson, Magnus; In 't Zandt, René LU ; Gisselsson, Anna; Hansson, Georg; Meier, Sebastian and Lerche, Mathilde H (2009) In Journal of Biological Chemistry 284(52). p.82-36077
Abstract

Mechanistic details of mammalian metabolism in vivo and dynamic metabolic changes in intact organisms are difficult to monitor because of the lack of spatial, chemical, or temporal resolution when applying traditional analytical tools. These limitations can be addressed by sensitivity enhancement technology for fast in vivo NMR assays of enzymatic fluxes in tissues of interest. We apply this methodology to characterize organ-specific short chain fatty acid metabolism and the changes of carnitine and coenzyme A pools in ischemia reperfusion. This is achieved by assaying acetyl-CoA synthetase and acetyl-carnitine transferase catalyzed transformations in vivo. The fast and predominant flux of acetate and propionate signal into... (More)

Mechanistic details of mammalian metabolism in vivo and dynamic metabolic changes in intact organisms are difficult to monitor because of the lack of spatial, chemical, or temporal resolution when applying traditional analytical tools. These limitations can be addressed by sensitivity enhancement technology for fast in vivo NMR assays of enzymatic fluxes in tissues of interest. We apply this methodology to characterize organ-specific short chain fatty acid metabolism and the changes of carnitine and coenzyme A pools in ischemia reperfusion. This is achieved by assaying acetyl-CoA synthetase and acetyl-carnitine transferase catalyzed transformations in vivo. The fast and predominant flux of acetate and propionate signal into acyl-carnitine pools shows the efficient buffering of free CoA levels. Sizeable acetyl-carnitine formation from exogenous acetate is even found in liver, where acetyl-CoA synthetase and acetyl-carnitine transferase activities have been assumed sequestered in different compartments. In vivo assays of altered acetate metabolism were applied to characterize pathological changes of acetate metabolism upon ischemia. Coenzyme pools in ischemic skeletal muscle are reduced in vivo even 1 h after disturbing muscle perfusion. Impaired mitochondrial metabolism and slow restoration of free CoA are corroborated by assays employing fumarate to show persistently reduced tricarboxylic acid (TCA) cycle activity upon ischemia. In the same animal model, anaerobic metabolism of pyruvate and tissue perfusion normalize faster than mitochondrial bioenergetics.

(Less)
Please use this url to cite or link to this publication:
author
publishing date
type
Contribution to journal
publication status
published
keywords
Acetylcarnitine, Animals, Carnitine, Citric Acid Cycle, Coenzyme A, Coenzyme A Ligases, Energy Metabolism, Fatty Acids, Fumarates, Liver, Mice, Mitochondria, Liver, Mitochondria, Muscle, Muscle, Skeletal, Organ Specificity, Reperfusion Injury, Journal Article, Research Support, Non-U.S. Gov't
in
Journal of Biological Chemistry
volume
284
issue
52
pages
6 pages
publisher
ASBMB
external identifiers
  • scopus:73649090022
ISSN
1083-351X
DOI
10.1074/jbc.M109.066407
language
English
LU publication?
no
id
8bf73c4b-4799-4925-bd37-927f044b729d
date added to LUP
2017-03-16 11:29:29
date last changed
2017-12-10 05:06:47
@article{8bf73c4b-4799-4925-bd37-927f044b729d,
  abstract     = {<p>Mechanistic details of mammalian metabolism in vivo and dynamic metabolic changes in intact organisms are difficult to monitor because of the lack of spatial, chemical, or temporal resolution when applying traditional analytical tools. These limitations can be addressed by sensitivity enhancement technology for fast in vivo NMR assays of enzymatic fluxes in tissues of interest. We apply this methodology to characterize organ-specific short chain fatty acid metabolism and the changes of carnitine and coenzyme A pools in ischemia reperfusion. This is achieved by assaying acetyl-CoA synthetase and acetyl-carnitine transferase catalyzed transformations in vivo. The fast and predominant flux of acetate and propionate signal into acyl-carnitine pools shows the efficient buffering of free CoA levels. Sizeable acetyl-carnitine formation from exogenous acetate is even found in liver, where acetyl-CoA synthetase and acetyl-carnitine transferase activities have been assumed sequestered in different compartments. In vivo assays of altered acetate metabolism were applied to characterize pathological changes of acetate metabolism upon ischemia. Coenzyme pools in ischemic skeletal muscle are reduced in vivo even 1 h after disturbing muscle perfusion. Impaired mitochondrial metabolism and slow restoration of free CoA are corroborated by assays employing fumarate to show persistently reduced tricarboxylic acid (TCA) cycle activity upon ischemia. In the same animal model, anaerobic metabolism of pyruvate and tissue perfusion normalize faster than mitochondrial bioenergetics.</p>},
  author       = {Jensen, Pernille R and Peitersen, Torben and Karlsson, Magnus and In 't Zandt, René and Gisselsson, Anna and Hansson, Georg and Meier, Sebastian and Lerche, Mathilde H},
  issn         = {1083-351X},
  keyword      = {Acetylcarnitine,Animals,Carnitine,Citric Acid Cycle,Coenzyme A,Coenzyme A Ligases,Energy Metabolism,Fatty Acids,Fumarates,Liver,Mice,Mitochondria, Liver,Mitochondria, Muscle,Muscle, Skeletal,Organ Specificity,Reperfusion Injury,Journal Article,Research Support, Non-U.S. Gov't},
  language     = {eng},
  month        = {12},
  number       = {52},
  pages        = {82--36077},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {Tissue-specific short chain fatty acid metabolism and slow metabolic recovery after ischemia from hyperpolarized NMR in vivo},
  url          = {http://dx.doi.org/10.1074/jbc.M109.066407},
  volume       = {284},
  year         = {2009},
}