Reactome | ASRGL1 hydrolyses aspartame to L-Asp, L-Phe

ASRGL1 hydrolyses aspartame to L-Asp, L-Phe

Stable Identifier

R-HSA-5696365

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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ASRGL1 hydrolyses aspartame to L-Asp, L-Phe

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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