title: Liver peroxisomal alanine:glyoxylate aminotransferase and the effects of mutations associated with Primary Hyperoxaluria Type I: An overview.
abstract: Liver peroxisomal alanine:glyoxylate aminotransferase (AGT) (EC 2.6.1.44) catalyses the conversion of l-alanine and glyoxylate to pyruvate and glycine, a reaction that allows glyoxylate detoxification. Inherited mutations on the AGXT gene encoding AGT lead to Primary Hyperoxaluria Type I (PH1), a rare disorder characterized by the deposition of calcium oxalate crystals primarily in the urinary tract. Here we describe the results obtained on the biochemical features of AGT as well as on the molecular and cellular effects of polymorphic and pathogenic mutations. A complex scenario on the molecular pathogenesis of PH1 emerges in which the co-inheritance of polymorphic changes and the condition of homozygosis or compound heterozygosis are two important factors that determine the enzymatic phenotype of PH1 patients. All the reported data represent relevant steps toward the understanding of genotype/phenotype correlations, the prediction of the response of the patients to the available therapies, and the development of new therapeutic approaches. This article is part of a Special Issue entitled: Cofactor-dependent proteins: evolution, chemical diversity and bio-applications.
authors.affiliation: Department of Life Sciences and Reproduction, Section of Biological Chemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Oppici
authors.affiliation: Department of Life Sciences and Reproduction, Section of Biological Chemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Montioli
authors.affiliation: Department of Life Sciences and Reproduction, Section of Biological Chemistry, University of Verona, Strada Le Grazie 8, 37134 Verona, Italy. Electronic address: barbara.cellini@univr.it.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cellini
mesh_terms: D000409:Alanine / Q000378:metabolism*; D006801:Humans; D006960:Hyperoxaluria, Primary / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D009154:Mutation; D020675:Peroxisomes / Q000201:enzymology*; D000637:Transaminases / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D000637:Transaminases; C023067:glyoxylate aminotransferase; C019635:Alanine-glyoxylate transaminase; D000409:Alanine
keywords: Alanine:glyoxylate aminotransferase; Pathogenic variant; Primary Hyperoxaluria; Pyridoxal 5′-phosphate; Rare disease