γ-Glu-Ala is an endogenous kokumi dipeptide composed of L-glutamic acid and L-alanine that has been found in P. roqueforti.1 It has also been found in several ripened cheeses, including Gouda, goat, and Milner cheeses. γ-Glu-Ala is a positive allosteric modulator of the calcium-sensing receptor (CaSR; EC50 = 4.8 µM in CaSR-expressing HEK293 cells).2 It induces glutathionuria in mice when administered at a dose of 4 mmol/kg.3 Plasma levels of γ-Glu-Ala are increased in malnourished neonatal mice.4 Increased serum levels of γ-Glu-Ala are positively associated with an increased risk of chronic kidney disease.5
1.Toelstede, S., and Hofmann, T.Kokumi-active glutamyl peptides in cheeses and their biogeneration by Penicillium roquefortiiJ. Agric. Food Chem.57(9)3738-3748(2009) 2.Broadhead, G.K., Mun, H.-C., Avlani, V.A., et al.Allosteric modulation of the calcium-sensing receptor by γ-glutamyl peptides: Inhibition of PTH secretion, suppression of intracellular cAMP levels, and a common mechanism of action with ?-amino acidsJ. Biol. Chem.286(11)8786-8797(2011) 3.Anderson, M.E., and Meister, A.Inhibition of γ-glutamyl transpeptidase and induction of glutathionuria by γ-glutamyl amino acidsProc. Natl. Acad. Sci. USA83(14)5029-5032(1986) 4.Preidis, G.A., Keaton, M.A., Campeau, P.M., et al.The undernourished neonatal mouse metabolome reveals evidence of liver and biliary dysfunction, inflammation, and oxidative stressJ. Nutr.144(3)273-281(2014) 5.Kim, H., Yu, B., Li, X., et al.Serum metabolomic signatures of plant-based diets and incident chronic kidney diseaseAm. J. Clin. Nutr.116(1)151-164(2022)