The role of alanine glyoxylate transaminase-2 (agxt2) in β-alanine and carnosine metabolism of healthy mice and humans.

Autor: Stautemas, Jan, Jarzebska, Natalia, Shan, Zhou Xiang, Blancquaert, Laura, Everaert, Inge, de Jager, Sarah, De Baere, Siegrid, Hautekiet, Arne, Volkaert, Anneke, Lefevere, Filip B. D., Martens-Lobenhoffer, Jens, Bode-Böger, Stefanie M., Kim, Chang Keun, Leiper, James, Weiss, Norbert, Croubels, Siska, Rodionov, Roman N., Derave, Wim
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Zdroj: European Journal of Applied Physiology; 2020, Vol. 120 Issue 12, p2749-2759, 11p
Abstrakt: Purpose: Chronic β-alanine supplementation leads to increased levels of muscle histidine-containing dipeptides. However, the majority of ingested β-alanine is, most likely, degraded by two transaminases: GABA-T and AGXT2. In contrast to GABA-T, the in vivo role of AGXT2 with respect to β-alanine metabolism is unknown. The purpose of the present work is to investigate if AGXT2 is functionally involved in β-alanine homeostasis. Methods: Muscle histidine-containing dipeptides levels were determined in AGXT2 overexpressing or knock-out mice and in human subjects with different rs37369 genotypes which is known to affect AGXT2 activity. Further, plasma β-alanine kinetic was measured and urine was obtained from subjects with different rs37369 genotypes following ingestion of 1400 mg β-alanine. Result: Overexpression of AGXT2 decreased circulating and muscle histidine-containing dipeptides (> 70% decrease; p < 0.05), while AGXT2 KO did not result in altered histidine-containing dipeptides levels. In both models, β-alanine remained unaffected in the circulation and in muscle (p > 0.05). In humans, the results support the evidence that decreased AGXT2 activity is not associated with altered histidine-containing dipeptides levels (p > 0.05). Additionally, following an acute dose of β-alanine, no differences in pharmacokinetic response were measured between subjects with different rs37369 genotypes (p > 0.05). Interestingly, urinary β-alanine excretion was 103% higher in subjects associated with lower AGXT2 activity, compared to subjects associated with normal AGXT2 activity (p < 0.05). Conclusion: The data suggest that in vivo, β-alanine is a substrate of AGXT2; however, its importance in the metabolism of β-alanine and histidine-containing dipeptides seems small. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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