Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drosophila of the repleta group have a duplication of the gene which encodes alcohol dehydrogenase (ADH). We report the nucleotide sequence of an 8.4-kb region of genomic DNA of Drosophila hydei which includes the entire Adh region. Analysis of this sequence reveals similarity in organization to the Adh region of Drosophila mojavensis and Drosophila mulleri of the mulleri subgroup, with three genes ordered 5' to 3', Adh-psi, Adh-2, Adh-1. Deletion of a nucleotide in the second codon of each pseudogene suggests that the first Adh duplication occurred before the divergence of the hydei and mulleri subgroups. However, Adh-1 and Adh-2 of D. hydei are significantly more alike than Adh-1 and Adh-2 of D. mojavensis. Models to account for the difference in similarity between the coding genes were tested by orthologous and paralogous comparisons of the extent of sequence divergence. A model which proposes that independent duplication events generated Adh-1 and Adh-2 in the two lineages is supported by these data. The D. hydei pseudogene is transcribed and the transcript is processed in a complex manner. An intron of greater than 6.2 kb exists between the first "coding" exon and an upstream exon which is approximately 250 nucleotides in length.
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PMID:Characterization of the structure and evolution of the Adh region of Drosophila hydei. 200 8

Chlordecone (Kepone), a toxic organochlorine pesticide, undergoes bioreduction to chlordecone alcohol in human liver. This reaction is controlled by a cytosolic enzyme, chlordecone reductase (CDR), which may be of the aldo-keto reductase family of xenobiotic metabolizing enzymes [Molowa et al. (1986) J. Biol. Chem. 261, 12624-12627]. To further investigate the primary structure and expression of CDR, we screened a library of human liver cDNAs cloned in the expression vector lambda gt11 and isolated an 800 bp cDNA that directed synthesis of a fusion protein recognized by polyclonal anti-CDR antibodies. Using this cDNA as a probe, we screened two human liver cDNA libraries and found several 1.2-kb cDNAs which would code for a polypeptide with 308 residues (35.8 kDa). However, a similar full-length cDNA, possibly the transcript of a pseudogene, contained an in-frame nonsense codon. The deduced protein sequence of CDR showed 65% similarity to the primary structure of human liver aldehyde reductase and 66% similarity to the inferred protein sequence of rat lens aldose reductase. A search of GenBank revealed significant nucleotide similarity to a cDNA coding for bovine lung prostaglandin f synthase and to a partial cDNA coding for frog lens rho-crystallin. Southern blot analysis of human genomic DNA displayed between 45 and 65 kilobases of DNA hybridizable to CDR cDNA and demonstrated several restriction fragment length polymorphisms among 26 individuals. Northern blot analysis of RNA from human, gerbil, rabbit, hamster, mouse, and rat livers disclosed hybridization with CDR cDNA only for the first three species.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isolation and characterization of cloned cDNAs encoding human liver chlordecone reductase. 218 32

Current information on the molecular structure of human alcohol dehydrogenase (ADH) genes is fragmentary. To characterize all ADH genes, we have isolated 63 ADH clones from human genomic libraries made from one individual. Fifty-nine clones have been classified into five previously known loci: ADH1 (18 clones), ADH2 (20 clones), and ADH3 class I (16 clones), ADH4 class II (4 clones), and ADH5 class III (1 clone). Sequencing of one of the remaining four unclassified clones, SY lambda ADHE38, about 1.1 kb in length, shows no introns and three frameshift mutations in the coding region, with a total of 10 internal termination codons. When its deduced amino acid sequence was compared with those of the class I, class II, and class III ADHs, the proportions of identical amino acids were 56.7%, 55.5%, and 88.7%, respectively, suggesting that the processed pseudogene was derived from an ADH5 gene. The duplication event seems to have occurred about 3.5 million years ago, and the pseudogene has undergone a rapid change since then.
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PMID:Cloning and sequencing of a processed pseudogene derived from a human class III alcohol dehydrogenase gene. 229 56

The D. melanogaster Adh gene is transcribed from two different promoters; a proximal (larval) promoter is active during late embryonic and larval stages, and a distal (adult) promoter is active primarily in third instar larvae and in adult flies (1). Genetic analyses suggest that several species of the mulleri subgroup (distant relatives of D. melanogaster) have two closely-linked Adh genes, Adh-1 and Adh-2, each of which expresses a different ADH protein (2). The temporal pattern of expression of Adh-1 and Adh-2 is similar to the expression of D. melanogaster Adh from the proximal and distal promoters (2,3,4). We are interested in the molecular basis for the pattern of Adh expression in the mulleri subgroup species and in the mechanism of the switch in Adh promoter utilization. For these reasons, we have studied the structure and transcription of the Adh locus of D. mulleri, a species of the mulleri subgroup. We show that the ADH-1 and ADH-2 proteins are expressed from two distinct genes separated by 2 kilobase pairs, and that Adh-1 and Adh-2 are transcribed in the expected temporal pattern. In addition, we find a pseudogene 1.2 kb upstream from Adh-2, which is transcribed in a temporal pattern similar to Adh-2.
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PMID:Structure and transcription of the Drosophila mulleri alcohol dehydrogenase genes. 299 30

Drosophila mojavensis and other species of the mulleri subgroup contain a duplicate gene encoding the enzyme alcohol dehydrogenase (ADH). Studies on the genetic relationship of the two genes using electrophoretic variants show them to be closely linked. We have cloned a 13.5-kb fragment of D. mojavensis DNA into the lambda vector, Charon 30. This fragment contains both Adh genes separated by approximately 2 kb of DNA. The clone hybridized to a single position on chromosome 3 in D. mojavensis following in situ hybridization. It is likely that the genes are tandemly arranged in the genome. One of the two genes shows a complexity in its structure that suggests the close linkage of a pseudogene or part of a gene. The structure of the Adh locus in five species of the mulleri subgroup have been compared by constructing restriction maps of genomic DNA. Two of these species D. arizonensis and D. mojavensis express Adh-1 in the ovaries; the others do not. In comparing these species it is evident that there has been one or two insertions into the region between the Adh genes. It is possible that one of these structural changes is related to the change in Adh tissue-specific expression that has occurred during the evolution of these species.
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PMID:Molecular genetic characterization of a locus that contains duplicate Adh genes in Drosophila mojavensis and related species. 300 Aug 66

The pattern of sites within purified DNA that are highly susceptible to double-stranded cleavage by micrococcal nuclease has been analyzed in the vicinity of over 20 genes from widely separated loci in Drosophila. These genes have uniformly exhibited a distinctive organization of cleavage sites such that at early times of digestion major sites are observed in the spacer regions surrounding the genes, but not within the protein coding regions themselves. Examples examined include Drosophila genes for heat-shock proteins, cytoplasmic actin, ribosomal protein 49, alcohol dehydrogenase, Sgs 4 glue protein, and other developmentally regulated transcripts, a human beta-globin gene, and mouse alpha 3-globin pseudogene. It seems probable that this gene/spacer pattern will be a general one in the genomes of eucaryotes, but not in the genomes of procaryotes, since neither pBR322 nor phage lambda DNA display such a pattern. One observes a nonrandom spacing of strong cleavage sites in Drosophila DNA, with the most frequent intervals being 195 bp and 411 bp. Such a pattern of variation in DNA structure may have evolved to facilitate the packaging of eucaryotic DNA into chromatin.
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PMID:Patterns of DNA structural polymorphism and their evolutionary implications. 631 4

The origin of new genes includes both the initial molecular events and subsequent population dynamics. A processed Drosophila alcohol dehydrogenase (Adh) gene, previously thought to be a pseudogene, provided an opportunity to examine the two phases of the origin of a new gene. The sequence of the processed Adh messenger RNA became part of a new functional gene by capturing several upstream exons and introns of an unrelated gene. This novel chimeric gene, jingwei, differs from its parent Adh gene in both its pattern of expression and rate of molecular evolution. Natural selection participated in the origin and subsequent evolution of this gene.
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PMID:Natural selection and the origin of jingwei, a chimeric processed functional gene in Drosophila. 768 12

Eleven rat genes have been assigned to rat chromosomes by use of mouse x rat somatic hybrids and/or use of linkage to known chromosome markers. Among them, the genes for the inducible nitric oxide synthase (Nos2) and for a vasoactive intestinal peptide receptor (Vipr) are potential candidates for genetic regulation of blood pressure and were localized to rat Chromosomes (Chrs) 10 and 8 respectively. Genes for gastric H,K-ATPase alpha subunit (Atp4a), Class I alcohol dehydrogenase (Adh), and aldolase C (Aldoc) were localized to Chrs 1, 2, and 10 respectively, and thus provide more DNA markers for genetic mapping of quantitative trait loci for blood pressure on those chromosomes. Genes for alkaline phosphatase (Alp1) and cardiac AE-3 Cl-/HCO3- exchanger (Ae3) were both localized to Chr 9. Genes for glutamate dehydrogenase (Glud) and gastric H,K-ATPase beta subunit (Atp4b) were localized to Chr 16. The ornithine decarboxylase (Odc) gene and ornithine decarboxylase pseudogene (Odcp) were localized to Chrs 6 and 11 respectively.
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PMID:Chromosomal assignment of 11 loci in the rat by mouse-rat somatic hybrids and linkage. 787 82

The Adh locus in Drosophila species which are members of the repleta group contains products of one or two duplication events. In all species examined to date one of the Adh genes is now a pseudogene, since mutations have rendered these genes incapable of being translated into a functional alcohol dehydrogenase. These pseudogenes contain introns in the standard Adh gene position; hence, their origin is not by retrotransposition. Comparison of the sequences of the Adh-psi from representatives of each of the subgroups of the repleta group reveal that the Adh pseudogene is present in each subgroup and that mutations at codon 2 and a deletion in the region immediately 5' to Adh-psi are common to all species. Therefore, it is likely that the translational inactivation event that resulted in a pseudogene occurred before the divergence of the species that make up the repleta group. We have investigated the transcription of Adh-psi of D. hydei and have found that the transcription has a developmental profile dissimilar from any known Adh gene, does not utilize an Adh promoter, and is initiated at a point almost 12 kb upstream. Comparison of sequence divergence of Adh-psi within species of the repleta group reveals that rates of evolution of the exons of Adh-psi are substantially slower than intergenic regions and are only slightly faster than those of exons of functional Adh genes. Second, retention of codon bias is found in the Adh-psi of most species, and substitution at synonymous coding positions substantially exceeds substitution at nonsynonymous coding positions. Comparison of the evolution of other putative pseudogenes with repleta group Adh pseudogenes suggests that at least some pseudogene sequences in Drosophila may be evolving through mechanisms and/or under influences not presently understood.
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PMID:Unusual molecular evolution of an Adh pseudogene in Drosophila. 801 38

Expression of the rat class I alcohol dehydrogenase (ADH) gene is highest in the liver and regions of the intestine. We characterized over 3 kilobases of the gene's 5'-flanking region by sequencing and transient transfection. Alignment of the flanking sequence of the rat gene with those of the mouse and human class I genes revealed a cis-acting element, known to be a functional glucocorticoid response element in the human gene and conserved in the mouse, is interrupted in the rat promoter by a 490-base pair processed retropseudogene of the ribosomal protein S25. Southern analysis indicated that this inserted element is present in the class I ADH promoters of multiple strains of rat. Transfection analysis of the rat and mouse promoters showed that the mouse, but not the rat promoter, is inducible by dexamethasone. Electrophoretic mobility shift assays using nuclear extracts from dexamethasone-treated cells confirmed that the mouse's element interacts with the glucocorticoid receptor. Transient transfection of the 5'-flanking region of the rat gene linked to a human growth hormone reporter demonstrated the liver and intestinal specificity of the rat promoter. Two positive elements, one from nucleotides -1,327 to -977 and the other from -241 to -12, were shown to support high levels of reporter activity. In addition, a suppressive element was localized between nucleotides -403 and -241, a region of DNA situated within the domain of the S25 ribosomal protein pseudogene.
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PMID:Characterization of the 5'-flanking sequence of rat class I alcohol dehydrogenase gene. 806 34


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