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)
- author
- Jensen, Pernille R
; Peitersen, Torben
; Karlsson, Magnus
; In 't Zandt, René
LU
; Gisselsson, Anna
; Hansson, Georg
; Meier, Sebastian
and Lerche, Mathilde H
- publishing date
- 2009-12-25
- 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
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:19861411
- 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
- 2024-04-28 09:10:52
@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}},
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}},
language = {{eng}},
month = {{12}},
number = {{52}},
pages = {{82--36077}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
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}},
doi = {{10.1074/jbc.M109.066407}},
volume = {{284}},
year = {{2009}},
}