Guanidino acid hydrolysis by the human enzyme annotated as agmatinase.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
21 12 2022
21 12 2022
Historique:
received:
10
08
2022
accepted:
19
12
2022
entrez:
21
12
2022
pubmed:
22
12
2022
medline:
24
12
2022
Statut:
epublish
Résumé
Guanidino acids such as taurocyamine, guanidinobutyrate, guanidinopropionate, and guanidinoacetate have been detected in humans. However, except for guanidionacetate, which is a precursor of creatine, their metabolism and potential functions remain poorly understood. Agmatine has received considerable attention as a potential neurotransmitter and the human enzyme so far annotated as agmatinase (AGMAT) has been proposed as an important modulator of agmatine levels. However, conclusive evidence for the assigned enzymatic activity is lacking. Here we show that AGMAT hydrolyzed a range of linear guanidino acids but was virtually inactive with agmatine. Structural modelling and direct biochemical assays indicated that two naturally occurring variants differ in their substrate preferences. A negatively charged group in the substrate at the end opposing the guanidine moiety was essential for efficient catalysis, explaining why agmatine was not hydrolyzed. We suggest to rename AGMAT as guanidino acid hydrolase (GDAH). Additionally, we demonstrate that the GDAH substrates taurocyamine, guanidinobutyrate and guanidinopropionate were produced by human glycine amidinotransferase (GATM). The presented findings show for the first time an enzymatic activity for GDAH/AGMAT. Since agmatine has frequently been proposed as an endogenous neurotransmitter, the current findings clarify important aspects of the metabolism of agmatine and guanidino acid derivatives in humans.
Identifiants
pubmed: 36543883
doi: 10.1038/s41598-022-26655-4
pii: 10.1038/s41598-022-26655-4
pmc: PMC9772407
doi:
Substances chimiques
agmatinase
EC 3.5.3.11
Agmatine
70J407ZL5Q
Guanidines
0
taurocyamine
543-18-0
Ureohydrolases
EC 3.5.3.-
AGMAT protein, human
EC 3.5.3.11
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22088Informations de copyright
© 2022. The Author(s).
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