title: Strict reaction and substrate specificity of AGXT2L1, the human O-phosphoethanolamine phospho-lyase.
abstract: Dysregulated expression of the AGXT2L1 gene has been associated to neuropsychiatric disorders. Recently the gene product was shown to possess O-phosphoethanolamine phospho-lyase activity. We here analyze the specificity of AGXT2L1 in terms of both reaction and substrate. We show that the enzyme, despite having evolved from a transaminase ancestor, is at least 500-fold more active as a lyase than as an aminotransferase. Furthermore, the lyase reaction is very selective for O-phosphoethanolamine, strongly discriminating against closely related compounds, and we dissect the factors that contribute to such narrow substrate specificity. Overall, AGXT2L1 function appears to be rigidly confined to phospholipid metabolism, which is altered in neuropsychiatric disturbances.
authors.affiliation: Department of Biosciences, University of Parma, Parma, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Schiroli
authors.forename: Simona
authors.initials: S
authors.lastname: Cirrincione
authors.forename: Stefano
authors.initials: S
authors.lastname: Donini
authors.forename: Alessio
authors.initials: A
authors.lastname: Peracchi
mesh_terms: D001714:Bipolar Disorder / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004983:Ethanolamines / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007700:Kinetics; D008190:Lyases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012559:Schizophrenia / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013379:Substrate Specificity; D000637:Transaminases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D004983:Ethanolamines; C005448:phosphorylethanolamine; D000637:Transaminases; C019635:Alanine-glyoxylate transaminase; D008190:Lyases