ASRGL1 hydrolyses aspartame to L-Asp, L-Phe

Stable Identifier
Reaction [transition]
Homo sapiens
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The human isoaspartyl peptidase/L-asparaginase (ASRGL1) is an N-terminal nucleophile (Ntn) hydrolase superfamily member that catalyses the hydrolysis of l-asparagine and beta-aspartyl-dipeptides and their methyl esters such as aspartame (beta-L-Asp-L-Phe methyl ester) (Cantor et al. 2009, Li et al. 2012, Nomme et al. 2014). ASRGL1 is a cytosolic enzyme that is active as a heterodimer of alpha and beta chains, formed by autocleavage between Gly167 and Thr168 (Nomme et al. 2012). ASRGL1 is expressed in brain, kidney, testis and the gastrointestinal tract. Aspartame is an artificial sweetner used as a sugar substitute in some drinks. Sufferers of phenylketonuria (PKU) are advised to avoid aspartame as one of its breakdown products, phenylalanine, could contribute to the excess pool of phenylalanine that PKU sufferers cannot metabolise from the body.
Literature References
PubMed ID Title Journal Year
22891768 Uncoupling intramolecular processing and substrate hydrolysis in the N-terminal nucleophile hydrolase hASRGL1 by circular permutation

Yang, S, Stone, EM, Agnello, G, Li, W, Georgiou, G, Chantranupong, L, Zhang, Y, Yogesha, SD, Cantor, JR, Liu, JQ

ACS Chem. Biol. 2012
22861376 Structures of apo and product-bound human L-asparaginase: insights into the mechanism of autoproteolysis and substrate hydrolysis

Konrad, M, Su, Y, Lavie, A, Nomme, J

Biochemistry 2012
24768817 Elucidation of the specific function of the conserved threonine triad responsible for human L-asparaginase autocleavage and substrate hydrolysis

Su, Y, Lavie, A, Nomme, J

J. Mol. Biol. 2014
19839645 The human asparaginase-like protein 1 hASRGL1 is an Ntn hydrolase with beta-aspartyl peptidase activity

Stone, EM, Georgiou, G, Chantranupong, L, Cantor, JR

Biochemistry 2009
Catalyst Activity

beta-aspartyl-peptidase activity of ASRGL1 heterodimer [cytosol]

Orthologous Events
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