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

ASRGL1 hydrolyses aspartame to L-Asp, L-Phe, MeOH

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, MeOH

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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 aspartyl-dipeptides and their methyl esters such as the artificial sweetener aspartame (alpha-L-Asp-L-Phe methyl ester), annotated here (Cantor et al. 2009, Li et al. 2012, Nomme et al. 2014). ASRGL1, localized to the cytosol, is active as a heterodimer formed by autocleavage between Gly167 and Thr168 (Nomme et al. 2012).

The enzyme is expressed in brain, kidney, testis and the gastrointestinal tract. Its physiological substrates are not known, and its role in aspartame metabolism may be limited in vivo, as most dietary aspartame is broken down by other known peptidases associated with intestinal microvilli (Hooper et al. 1994).

Literature References

PubMed ID	Title	Journal	Year
8141778	Metabolism of aspartame by human and pig intestinal microvillar peptidases Tieku, S, Hesp, RJ, Hooper, NM	Biochem J	1994
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
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
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