Gene Structure, Chromosomal Location, and Expression Pattern of Maleylacetoacetate Isomerase

• Published in: Genomics (San Diego, Calif.) Vol. 58; no. 3; pp. 263 - 269
• Main Authors: Fernández-Cañón, José Manuel, Hejna, Jim, Reifsteck, Carol, Olson, Susan, Grompe, Markus
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 15.06.1999; Elsevier
• Subjects: Alleles; Amino Acid Metabolism, Inborn Errors - enzymology; Amino Acid Metabolism, Inborn Errors - genetics; Amino Acid Sequence; Aminoacid disorders; Animals; Base Sequence; Biological and medical sciences; Blotting, Northern; Chromosome Banding; Chromosome Mapping; Chromosomes, Human, Pair 14 - genetics; cis-trans-Isomerases - genetics; DNA - chemistry; DNA - genetics; Errors of metabolism; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; gene structure; Genes - genetics; Genes. Genome; Genetic Variation; Humans; In Situ Hybridization, Fluorescence; liver failure; Male; maleylacetoacetate isomerase; Medical sciences; Metabolic diseases; Mice; Mice, Inbred C57BL; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Promoter Regions, Genetic; pseudotyrosinemia; RNA - genetics; RNA - metabolism; Sequence Alignment; Sequence Analysis, DNA; Sequence Homology, Amino Acid; Tissue Distribution; Tyrosine - blood; gene structure; liver failure; maleylacetoacetate isomerase; pseudotyrosinemia; Genetic mapping; Human; Tyrosinemia; Enzyme; Deficiency; Rodentia; Metabolic diseases; Chromosome D14; Gene organization; Gene expression; Enzymopathy; Genetic disease; Liver failure; Vertebrata; Maleylacetoacetate isomerase; Isomerases; Mammalia; Gene; Mouse; Mutation; cis-trans-Isomerases; Aminoacid disorder; Polymorphism
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.1999.5832

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 ∼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.