Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Human gastric alcohol dehydrogenase (sigma sigma-ADH) was submitted to peptide analysis at picomole scale. A total of 72 positions were determined in the protein chain, providing information on three aspects of alcohol dehydrogenase structures in general. First, the data establish the presence of a unique class of the enzyme, now confirmed as class IV, expressed in gastric tissue and separate from another novel class, now termed class V. Second, the class IV gastric enzyme has active site relationships compatible with an ethanol-active, zinc-containing alcohol dehydrogenase. Third, this enzyme class is of the variable type, like that for the 'variable', classical liver alcohol dehydrogenase of class I, and in contrast to that for the 'constant' class III enzyme. Known human alcohol dehydrogenase structures now prove the presence of at least seven human genes for the enzyme and nine for the whole protein family.
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PMID:Class IV alcohol dehydrogenase (the gastric enzyme). Structural analysis of human sigma sigma-ADH reveals class IV to be variable and confirms the presence of a fifth mammalian alcohol dehydrogenase class. 159 18

Humans possess five classes of alcohol dehydrogenase (ADH), including forms able to oxidize ethanol or formaldehyde as part of a defense mechanism, as well as forms acting as retinol dehydrogenases in the synthesis of the regulatory ligand retinoic acid. However, the mouse has previously been shown to possess only three forms of ADH. Hybridization analysis of mouse genomic DNA using cDNA probes specific for each of the five classes of human ADH has now indicated that mouse DNA cross-hybridizes to only classes I, III, and IV. With human class II or class V ADH cDNA probes, hybridization to mouse genomic DNA was very weak or undetectable, suggesting either a lack of these genes in the mouse or a high degree of mutational divergence relative to the human genes. cDNAs for murine ADH classes I and III have previously been cloned, and we now report the cloning of a full-length mouse class IV ADH cDNA. In Northern blot analyses, mouse class IV ADH mRNA was abundant in the stomach, eye, skin, and ovary, thus correlating with the expression pattern for the mouse Adh-3 gene previously determined by enzyme analysis. In situ hybridization studies on mouse stomach indicated that class IV ADH transcripts were abundant in the mucosal epithelium but absent from the muscular layer. Comparison of the expression patterns for all three mouse ADH genes indicated that class III was expressed ubiquitously, whereas classes I and IV were differentially expressed in an overlapping set of tissues that all contain a large component of epithelial cells. This expression pattern is consistent with the ability of classes I and IV to oxidize retinol for the synthesis of retinoic acid known to regulate epithelial cell differentiation. The results presented here indicate that the mouse has a simpler ADH gene family than the human but has conserved class IV ADH previously shown to be a very active retinol dehydrogenase in humans.
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PMID:Cloning of the mouse class IV alcohol dehydrogenase (retinol dehydrogenase) cDNA and tissue-specific expression patterns of the murine ADH gene family. 773 26

A partial human stomach alcohol dehydrogenase (ADH) encoding cDNA has been isolated, cloned, and sequenced, which contains 222 nucleotides encoding amino acid residues 227-299 of the ADH subunit. The amino acid sequence deduced from this cDNA was highly homologous with the rat stomach class IV ADH sequence recently reported (81.1% sequence identity). Homology with other human ADH classes was also observed: class I, 58.1% sequence identity; class II, 39.2% sequence identity; class III, 55.4% sequence identity; and class V, 50.0% sequence identity. These results support a proposal that the isolated cDNA encodes a partial sequence for human stomach class IV ADH. This sequence retains val294 for all other human ADH classes reported, as compared with an ala294 at this position reported for rat class IV ADH. This ala residue may contribute to the very high Km values with ethanol for the latter enzyme. In addition, three substitutions are reported for key residues in the coenzyme binding site: 251, gln/ser; 260, gly/asn; and 261, gly/asn, which may contribute to the weak coenzyme binding properties reported for human class IV ADH.
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PMID:Human stomach class IV alcohol dehydrogenase: molecular genetic analysis. 777 49

Alcohol dehydrogenases constitute a complex system of enzymes, classes, isozymes, and allelic variants. The zinc containing, well-known liver enzyme is a class I medium-chain alcohol dehydrogenase. Other classes of this family include the class II protein, the glutathione-dependent formaldehyde dehydrogenase (the class III enzyme), the stomach-expressed class IV form, and the recently defined class V protein. Characterized forms suggest that the glutathione-dependent formaldehyde dehydrogenase is the original ancestor, defining a role for the whole protein family in cellular defense mechanisms. The isozyme-multiple class I protein is derived from an early gene duplication, allowing sub-specialization in vertebrates. Class IV is the one most ethanol-active and appears to be derived from the class I line. Allelic variants within class I, in association with aldehyde dehydrogenase variants, correlate with population differences in ethanol metabolism and hence with susceptibility to develop alcohol-related diseases. The structures also correlate with functional properties and define molecular building units for the whole family.
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PMID:The alcohol dehydrogenase system. 803 53

A novel human alcohol dehydrogenase (ADH) gene called ADH7 has been characterized and determined to encode class IV ADH, an ADH isozyme which is very active as a retinol dehydrogenase. A nearly full-length cDNA for ADH7 was isolated from a human stomach cDNA library, and a 5' genomic clone containing exons 1 and 2 was isolated from a human genomic library. DNA sequence analysis of the cDNA and genomic clones revealed the complete coding region of the gene and the deduced full-length amino acid sequence of human class IV ADH composed of 373 amino acids following the initiator methionine. The class IV identity of the sequence was confirmed by agreement with previously determined sequences for several human stomach class IV ADH peptides. Alignment of the full-length predicted amino acid sequence of human class IV ADH with the full-length sequences of the other four known human ADH classes revealed sequence identities of 69% (class I), 59% (class II), 61% (class III), and 60% (class V). The higher sequence identity shared with human class I ADH suggests that the genes for ADH classes I and IV may have diverged from a common ancestor after the separation of the other classes, and may still share common physiological functions. Discussed is the possibility that one of these functions is retinol oxidation for the synthesis of retinoic acid, a hormone important for cellular differentiation.
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PMID:The complete structure of human class IV alcohol dehydrogenase (retinol dehydrogenase) determined from the ADH7 gene. 819 8

The amounts of mRNA expressed for different alcohol dehydrogenase (ADH) classes were determined in human tissues by Northern hybridization. ADH classes I, II, and III were expressed in all tissues. The mRNAs were highest for class I ADHs, with particularly strong signals in liver, lung, ileum, colon, and uterus. For class II ADH, such a wide tissue distribution had not been recognized previously. Expression of class III ADH was highest in testis, followed by uterus, colon, and ileum. The amounts of class I and III ADH mRNAs varied significantly, indicating that tissue-specific factors modulate the expression of these enzymes above a basal level. Class V ADH (ADH6) was not detected in any of the tissues, including stomach. This suggests that class V ADH is not identical with human stomach sigma-ADH (class IV). The results support the general proposition that ADHs are not restricted to liver and have functions other than those in ethanol oxidation.
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PMID:Extrahepatic, differential expression of four classes of human alcohol dehydrogenase. 850 36

Tissue distribution of the five identified classes of human alcohol dehydrogenase was studied by assessment of mRNA levels in 23 adult and four fetal tissues. Alcohol dehydrogenase of class I was found in most tissues, brain and placenta excluded, but expression levels among tissues differed widely. The distribution pattern of class III transcripts was consistent with those of housekeeping enzymes while, in contrast, class IV transcripts were found only in stomach. Transcripts of multiple length were detected for most classes and were due to different gene products arising through the use of different poly-A signals or transcription from different gene loci. Both class II and class V showed a pattern of liver-enriched expression. However, low mRNA levels were detected also in stomach, pancreas and small intestine for class II, and in fetal kidney and small intestine for class V. Significantly higher levels of class V transcripts were present in fetal liver when compared with levels in adult liver, which suggests that human class V is a predominantly fetal alcohol dehydrogenase.
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PMID:Alcohol dehydrogenase in human tissues: localisation of transcripts coding for five classes of the enzyme. 895 75

Screens were made for alcohol dehydrogenase (ADH) of the classical type (the MDR superfamily) in translations of human and other relevant genomes, corresponding to the organism types from which the enzyme was initially purified. Considerable multiplicities were detected in the dimeric enzymes from higher eukaryotes: seven forms in the human (plus three pseudogenes), all genes on chromosome 4, in the order class IV --> class Igamma --> class Ibeta --> class Ialpha --> class V --> class II --> class III, and eight forms in Arabidopsis thaliana (plus one pseudogene). These multiplicity patterns, and the species variability in the animal (human/mouse) and plant (Arabidopsis/pea) lines, suggest parallel but separate duplicatory events, giving rise to three families of dimeric MDR-ADH: class III, the animal non-class III, and the plant non-class III enzymes, with functions in formaldehyde elimination, in alcohol/aldehyde detoxication and in special pathways in higher eukaryotes. Multiplicity, although to a lesser extent, was also noted in tetrameric MDR-ADH, suggesting functional divergence between the dimeric and tetrameric enzymes. Combining these observations, at least five levels of divergence are reflected in the present ADH forms, corresponding to nodes at the SDR/MDR, the dimer/tetramer, the class III/non-class III, the class I/P, and the more recent class splits, each branch associated with separate functional patterns.
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PMID:Differential multiplicity of MDR alcohol dehydrogenases: enzyme genes in the human genome versus those in organisms initially studied. 1216 18

The alcohol dehydrogenase enzymes in mice and humans are encoded by a linked group of genes in the same transcriptional orientation. The enzymes play important roles in alcohol metabolism and retinoid signaling and homeostasis. The expression patterns at the mRNA level of the mouse Adh4 (class II) gene and the recently identified Adh6a and Adh6b genes (class V) are now reported to complete this analysis for the entire family. Adh4 is expressed at high levels in liver and is detectable in small intestine and testes. Adh6b is expressed in liver but Adh6a is not. Adh6a is expressed at high levels in small intestine while Adh6b is not. Adh6a expression is detectable in the female adrenal and not at all in the male adrenal, but Adh6b is expressed at moderate levels in both sexes. Although Adh6a and Adh6b have expression patterns different from each other, neither expresses like any other gene in the complex, suggesting different control mechanisms and possibly different functions.
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PMID:Tissue expression pattern of class II and class V genes found in the Adh complex on mouse chromosome 3. 1880 46

Mammalian alcohol dehydrogenase (ADH) can be divided into six classes, ADH1-ADH6, according to primary structure and function, where the classes are further subdivided into isozymes and allelic forms. With the increasing amount of available genomic data a general pattern is possible to trace within the mammalian ADH gene and protein families. The transcriptional order for the ADH genes in all mammalian genomes is the same (ADH4-ADH1-ADH6-ADH5-ADH2-ADH3), but the cluster is found on different chromosomes in different species. However, in primates only ADH1-ADH5 are present, where the loss of ADH6 may have occurred simultaneously as the split into ADH1 isoforms. ADH3, also denoted glutathione-dependent formaldehyde dehydrogenase and S-nitrosoglutathione reductase, is identified as the last gene in the ADH transcriptional order, but several pseudogenes for ADH3 have been traced at other chromosomes. The flanking genes outside the ADH genome are similar or identical for all species showing that a larger DNA region has been duplicated and further evolved. However, the only entirely completed ADH genomes are those from primates and rodents. The latest identified ADH forms, ADH5 (class V) and ADH6 (class VI), are truly different classes and both are very diverged in contrast to ADH3, which is the most conserved class of all ADHs. ADH5 and ADH6 have been identified at the gene and transcriptional levels only, and their functions are still an enigma.
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PMID:Mammalian alcohol dehydrogenases--a comparative investigation at gene and protein levels. 2129 72


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