title: Gene structure, chromosomal location, and expression pattern of maleylacetoacetate isomerase.
abstract: The gene for maleylacetoacetate isomerase (MAAI) (EC 5.2.1.2) was the last gene in the mammalian phenylalanine/tyrosine catabolic pathway to be cloned. We have isolated the human and murine genes and determined their genomic structure. The human gene spans a genomic region of approximately 10 kb, has 9 exons ranging from 50 to 528 bp in size, and was mapped to 14q24.3-14q31.1 using fluorescence in situ hybridization. The complete catabolic pathway of phenylalanine/tyrosine is normally restricted to liver and kidney, but the maleylacetoacetate isomerase gene is expressed ubiquitously. This suggests a possible second role for the MAAI protein different from phenylalanine/tyrosine catabolism. We have searched for mutations in the maleylacetoacetate isomerase gene in four cases of unexplained severe liver failure in infancy with clinical similarities to hereditary tyrosinemia type I (pseudotyrosinemia). Several amino acid changes were identified, but all were found to retain MAAI activity and thus represent protein polymorphisms. We conclude that MAAI deficiency is not a common cause of the pseudotyrosinemic phenotype.
authors.affiliation: Department of Molecular and Medical Genetics, Department of Pediatrics, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97201, USA. fernandj@ohsu.edu
authors.forename: J M
authors.initials: JM
authors.lastname: Fernández-Cañón
authors.forename: J
authors.initials: J
authors.lastname: Hejna
authors.forename: C
authors.initials: C
authors.lastname: Reifsteck
authors.forename: S
authors.initials: S
authors.lastname: Olson
authors.forename: M
authors.initials: M
authors.lastname: Grompe
mesh_terms: D000483:Alleles; D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D015870:Gene Expression; D005796:Genes / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012313:RNA / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution; D014443:Tyrosine / Q000097:blood; D019745:cis-trans-Isomerases / Q000235:genetics*
chemical_list: D014443:Tyrosine; D012313:RNA; D004247:DNA; D019745:cis-trans-Isomerases; C021531:maleylacetoacetate isomerase