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Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by β-alanine transamination

Laura Blancquaert UGent, Shahid P Baba, Sebastian Kwiatkowski, Jan Stautemas UGent, Sanne Stegen, Silvia Barbaresi UGent, Weiliang Chung UGent, Adjoa A Boakye, J David Hoetker, Aruni Bhatnagar, et al. (2016) JOURNAL OF PHYSIOLOGY-LONDON. 594(17). p.4849-4863
abstract
The metabolic fate of orally ingested beta-alanine is largely unknown. Chronic beta-alanine supplementation is becoming increasingly popular for improving high-intensity exercise performance because it is the rate-limiting precursor of the dipeptide carnosine (beta-alanyl-L-histidine) in muscle. However, only a small fraction (3-6%) of the ingested beta-alanine is used for carnosine synthesis. Thus, the present study aimed to investigate the putative contribution of two beta-alanine transamination enzymes, namely 4-aminobutyrate-2-oxoglutarate transaminase (GABA-T) and alanine-glyoxylate transaminase (AGXT2), to the homeostasis of carnosine and its methylated analogue anserine. We found that, when transfected into HEK293T cells, recombinant mouse and human GABA-T and AGXT2 are able to transaminate beta-alanine efficiently. The reaction catalysed by GABA-T is inhibited by vigabatrin, whereas both GABA-T and AGXT2 activity is inhibited by aminooxyacetic acid (AOA). Both GABA-T and AGXT2 are highly expressed in the mouse liver and kidney and the administration of the inhibitors effectively reduced their enzyme activity in liver (GABA-T for vigabatrin; GABA-T and AGXT2 for AOA). In vivo, injection of AOA in C57BL/6 mice placed on beta-alanine (0.1% w/v in drinking water) for 2 weeks lead to a 3-fold increase in circulating beta-alanine levels and to significantly higher levels of carnosine and anserine in skeletal muscle and heart. By contrast, specific inhibition of GABA-T by vigabatrin did not affect carnosine and anserine levels in either tissue. Collectively, these data demonstrate that homeostasis of carnosine and anserine in mammalian skeletal muscle and heart is controlled by circulating beta-alanine levels, which are suppressed by hepatic and renal beta-alanine transamination upon oral beta-alanine intake.
Please use this url to cite or link to this publication:
author
organization
alternative title
Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by beta-alanine transamination
year
type
journalArticle (original)
publication status
published
subject
keyword
GAMMA-AMINOBUTYRIC-ACID, ALPHA-KETOGLUTARIC ACID, HUMAN VASTUS LATERALIS, 4-AMINO-HEX-5-ENOIC ACID, AMINOOXYACETIC ACID, BRAIN GABA, AMINOTRANSFERASE, SUPPLEMENTATION, METABOLISM, INHIBITION
journal title
JOURNAL OF PHYSIOLOGY-LONDON
J. Physiol.-London
volume
594
issue
17
pages
4849 - 4863
Web of Science type
Article
Web of Science id
000383571100022
JCR category
PHYSIOLOGY
JCR impact factor
4.739 (2016)
JCR rank
9/84 (2016)
JCR quartile
1 (2016)
ISSN
0022-3751
DOI
10.1113/JP272050
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
7276339
handle
http://hdl.handle.net/1854/LU-7276339
date created
2016-06-21 11:03:18
date last changed
2017-07-26 10:10:00
@article{7276339,
  abstract     = {The metabolic fate of orally ingested beta-alanine is largely unknown. Chronic beta-alanine supplementation is becoming increasingly popular for improving high-intensity exercise performance because it is the rate-limiting precursor of the dipeptide carnosine (beta-alanyl-L-histidine) in muscle. However, only a small fraction (3-6\%) of the ingested beta-alanine is used for carnosine synthesis. Thus, the present study aimed to investigate the putative contribution of two beta-alanine transamination enzymes, namely 4-aminobutyrate-2-oxoglutarate transaminase (GABA-T) and alanine-glyoxylate transaminase (AGXT2), to the homeostasis of carnosine and its methylated analogue anserine. We found that, when transfected into HEK293T cells, recombinant mouse and human GABA-T and AGXT2 are able to transaminate beta-alanine efficiently. The reaction catalysed by GABA-T is inhibited by vigabatrin, whereas both GABA-T and AGXT2 activity is inhibited by aminooxyacetic acid (AOA). Both GABA-T and AGXT2 are highly expressed in the mouse liver and kidney and the administration of the inhibitors effectively reduced their enzyme activity in liver (GABA-T for vigabatrin; GABA-T and AGXT2 for AOA). In vivo, injection of AOA in C57BL/6 mice placed on beta-alanine (0.1\% w/v in drinking water) for 2 weeks lead to a 3-fold increase in circulating beta-alanine levels and to significantly higher levels of carnosine and anserine in skeletal muscle and heart. By contrast, specific inhibition of GABA-T by vigabatrin did not affect carnosine and anserine levels in either tissue. Collectively, these data demonstrate that homeostasis of carnosine and anserine in mammalian skeletal muscle and heart is controlled by circulating beta-alanine levels, which are suppressed by hepatic and renal beta-alanine transamination upon oral beta-alanine intake.},
  author       = {Blancquaert, Laura and Baba, Shahid P and Kwiatkowski, Sebastian and Stautemas, Jan and Stegen, Sanne and Barbaresi, Silvia and Chung, Weiliang and Boakye, Adjoa A and Hoetker, J David and Bhatnagar, Aruni and Delanghe, Joris and Vanheel, Bert and Veiga-da-Cunha, Maria and Derave, Wim and Everaert, Inge},
  issn         = {0022-3751},
  journal      = {JOURNAL OF PHYSIOLOGY-LONDON},
  keyword      = {GAMMA-AMINOBUTYRIC-ACID,ALPHA-KETOGLUTARIC ACID,HUMAN VASTUS LATERALIS,4-AMINO-HEX-5-ENOIC ACID,AMINOOXYACETIC ACID,BRAIN GABA,AMINOTRANSFERASE,SUPPLEMENTATION,METABOLISM,INHIBITION},
  language     = {eng},
  number       = {17},
  pages        = {4849--4863},
  title        = {Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by \ensuremath{\beta}-alanine transamination},
  url          = {http://dx.doi.org/10.1113/JP272050},
  volume       = {594},
  year         = {2016},
}

Chicago
Blancquaert, Laura, Shahid P Baba, Sebastian Kwiatkowski, Jan Stautemas, Sanne Stegen, Silvia Barbaresi, Weiliang Chung, et al. 2016. “Carnosine and Anserine Homeostasis in Skeletal Muscle and Heart Is Controlled by Β-alanine Transamination.” Journal of Physiology-london 594 (17): 4849–4863.
APA
Blancquaert, L., Baba, S. P., Kwiatkowski, S., Stautemas, J., Stegen, S., Barbaresi, S., Chung, W., et al. (2016). Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by β-alanine transamination. JOURNAL OF PHYSIOLOGY-LONDON, 594(17), 4849–4863.
Vancouver
1.
Blancquaert L, Baba SP, Kwiatkowski S, Stautemas J, Stegen S, Barbaresi S, et al. Carnosine and anserine homeostasis in skeletal muscle and heart is controlled by β-alanine transamination. JOURNAL OF PHYSIOLOGY-LONDON. 2016;594(17):4849–63.
MLA
Blancquaert, Laura, Shahid P Baba, Sebastian Kwiatkowski, et al. “Carnosine and Anserine Homeostasis in Skeletal Muscle and Heart Is Controlled by Β-alanine Transamination.” JOURNAL OF PHYSIOLOGY-LONDON 594.17 (2016): 4849–4863. Print.