Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.5.1.18 (glutathione S-transferase)
 22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report here the first characterization of a gene encoding a homogentisate dioxygenase, the Aspergillus nidulans hmgA gene. The HmgA protein catalyzes an essential step in phenylalanine catabolism, and disruption of the gene results in accumulation of homogentisate in broths containing phenylalanine. hmgA putatively encodes a 448-residue polypeptide (Mr = 50,168) containing 21 histidine and 23 tyrosine residues. This polypeptide has been expressed in Escherichia coli as a fusion to glutathione S-transferase, and the affinity-purified protein has homogentisate dioxygenase activity. A. nidulans, an ascomycete amenable to classical and reverse genetic analysis, is a good metabolic model to study inborn errors in human Phe catabolism. One such disease, alkaptonuria, was the first human inborn error recognized (Garrod, A. E. (1902) Lancet 2, 1616-1620) and results from loss of homogentisate dioxygenase. Here we take advantage of the high degree of conservation between the amino acid sequences of the fungal and higher eukaryote enzymes of this pathway to identify expressed sequence tags encoding human and plant homologues of HmgA. This is a significant advance in characterizing the genetic defect(s) of alkaptonuria and illustrates the usefulness of our fungal model.
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PMID:Molecular characterization of a gene encoding a homogentisate dioxygenase from Aspergillus nidulans and identification of its human and plant homologues. 767 53

Tyrosine catabolism is an essential pathway in animals, but its role in plants is unclear. The first steps of tyrosine degradation lead to the formation of homogentisate. In animals this is then sequentially acted on by homogentisate dioxygenase (HGO), maleylacetoacetate isomerase (MAAI) and fumarylacetoacetate hydrolase (FAH) to generate fumarate and acetoacetate. In plants, homogentisate is used to generate the essential redox metabolites tocopherol and plastoquinone, which effectively act as an alternative metabolic fate for tyrosine. Having determined that a zeta class glutathione transferase from Arabidopsis thaliana is a functional MAAI, we have looked for evidence that the mammalian degradation pathway could also operate in plants. Based on array and quantitative PCR experiments, the A. thaliana homologues AtHGO, AtMAAI and AtFAH could be shown to be expressed, with AtHGO and AtMAAI showing evidence of co-regulation. cDNAs encoding AtHGO, AtMAAI and AtFAH were cloned in Escherichia coli and shown to represent a fully functional catabolic pathway when combined in vitro. The significance of this pathway, including increased transcription of the associated enzymes in senescing tissue, compartmentalisation and impact on flux into synthesis of Vitamin E and other tocopherols of biotechnological interest is discussed.
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PMID:Enzymes of tyrosine catabolism in Arabidopsis thaliana. 2298 Feb 5