Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1332347 (ADH)
 2,230 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human chi-alcohol dehydrogenase (chi-ADH) is a zinc-containing dimeric enzyme responsible for the oxidation of long-chain alcohols and omega-hydroxyfatty acids. Class-III ADHs, of which chi-ADH is the prototype, are widely produced and well conserved during evolution. This suggests that they fulfill important housekeeping roles in cellular metabolism. Recent evidence suggests that class-III ADH and formaldehyde dehydrogenase (FDH) are the same enzyme. We have isolated and characterized two overlapping genomic clones that cover the entire ADH5 (FDH) gene. ADH5 is composed of nine exons and eight introns. Two major transcription start points were identified by primer extension. The 5' nontranslated region is unusual in that it contains two additional upstream ATG codons, which would encode peptides of 20 and 10 amino acids. Neither of the upstream ATGs is in a good context for translation initiation, whereas the ATG initiating &khgr;-ADH is in a favorable context. The 5' region of ADH5 is a CpG island; it is extremely G+C rich and has many CpG doublets. It does not contain either a TATA box or a CAAT box. This is consistent with ubiquitous expression, and contrasts with the promoters of all previously cloned ADH genes, which are expressed in a tissue-specific manner. The 5' region of ADH5 contains consensus binding sites for the transcriptional regulatory proteins, Sp1, AP2, LF-A1, NF-1, NF-A2, and NF-E1. A 1.5-kb upstream fragment from ADH5 was able to drive the transcription of a cat reporter gene at high levels in monkey kidney cells (CV-1). Several processed pseudogenes were also isolated.
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PMID:Cloning and characterization of the ADH5 gene encoding human alcohol dehydrogenase 5, formaldehyde dehydrogenase. 144 28

The human alcohol dehydrogenase (ADH; alcohol:NAD+ oxidoreductase, EC 1.1.1.1) gene family consists of five known loci (ADH1-ADH5), which have been mapped close together on chromosome 4 (4q21-25). ADH isozymes encoded by these genes are grouped in three distinct classes in terms of their enzymological properties. A moderate structural similarity is observed between the members of different classes. We isolated an additional member of the ADH gene family by means of cross-hybridization with the ADH2 (class I) cDNA probe. cDNA clones corresponding to this gene were derived from PCR-amplified libraries as well. The coding sequence of a 368-amino-acid-long open reading frame was interrupted by introns into eight exons and spanned approximately 17 kilobases on the genome. The gene contains a glucocorticoid response element at the 5' region. The transcript was detected in the stomach and liver. The deduced amino acid sequence of the open reading frame showed about 60% positional identity with known human ADHs. This extent of homology is comparable to interclass similarity in the human ADH family. Thus, the newly identified gene, which is designated ADH6, governs the synthesis of an enzyme that belongs to another class of ADHs presumably with a distinct physiological role.
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PMID:A human alcohol dehydrogenase gene (ADH6) encoding an additional class of isozyme. 188 1

Rabbit immune sera raised against denatured forms of horse liver alcohol dehydrogenase and of human ADH5 isozyme were found to react with the denatured subunits of all the human ADH isozymes regardless of their class. The immune serum against the human ADH isozyme cross-reacted also with horse ADH subunits and, at appropriate dilutions, both the immune sera reacted with denatured yeast ADH, suggesting that common structures have been preserved in these molecules over a long evolutionary period. The immune sera partially reacted also with the respective antigens in their native conformation, indicating that some 'sequential' epitopes are expressed on the surface of the folded proteins.
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PMID:Immunological cross-reactivity of alcohol dehydrogenase (ADH) isozymes with rabbit immune sera against horse and human ADH subunits. 245 67

A cDNA encoding human class III (chi ADH5) alcohol dehydrogenase was isolated, sequenced and used to comparatively map this unusual ADH. In their coding sequences, the three major ADH classes were approximately equisimilar, class II and III ADHs sharing the highest sequence identity (67%). A class III-like ADH was mapped to mouse chromosome 3, site of the ADH gene complex, and synteny of ADH5 with four other ADH loci on human chromosome 4 was confirmed. The nearly full-length 1613 nucleotide cDNA contained 433 nucleotides of 3' nontranslated sequence and two possible initiation sites for translation. A protein of 374 amino acid residues could be synthesized using the potential initiation codon at nucleotide 59. However, use of the likely initiation codon at nucleotide 5 would produce a protein of 392 residues with 19 additional N-terminal residues as compared to the known protein sequence. The derived protein sequence also differs at residue 166, where Tyr is found. This difference, due to a single base substitution, could result from cloning artifact, polymorphism, or two expressed class III ADH genes.
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PMID:Cloning and comparative mapping of a human class III (chi) alcohol dehydrogenase cDNA. 267 57

The recently identified chi-ADH isozyme was purified from human liver and used to raise immune sera. The chi form of ADH showed no structural resemblance to the ADH1, ADH2 and ADH3 (class I) or ADH4 (class II) isozymes, as judged by its immunological properties. chi-ADH was found in most human tissues including fetal specimens of 16 weeks gestational age and showed a preference for long chain primary alcohols with a double bond in the beta position. We conclude that the locus, designated ADH5, encoding the chi isozyme has a separate evolutionary origin from the other ADH genes.
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PMID:Immunological and biochemical characterization of the human alcohol dehydrogenase chi-ADH isozyme. 642 46

A chromosome band 4q21 gene (MLLT2, formerly called AF-4/FEL) involved in a reciprocal translocation with chromosome band 11q23 in t(4;11) acute leukemia has been cloned. To provide better definition of gene order and relationships in this region where MLLT2 resides, we used pulsed field gel electrophoresis (PFGE) to investigate 13 genes (including MLLT2) with physical locations in bands 4q11-->q25. Somatic cell hybrids derived from RS4;11, a leukemic cell line carrying the t(4;11)(q21;q23), were also used to localize genes in relation to MLLT2. Linkage of the interleukin 8 (IL8), albumin (ALB), and platelet factor 4 (PF4) genes was confirmed by NotI, SalI and SacII digests. The maximum distance between PF4 and ALB is 210 kb and between ALB and IL8 is 420 kb. The alcohol dehydrogenase, class I (ADH2, ADH3) gene cluster can be linked to the alcohol dehydrogenase, class III gene (ADH5) by SacII, NruI, and EagI digests. The maximum distance between them is 590 kb. Our study indicated that ALB, alpha-fetoprotein (AFP), PF4, beta-thromboglobulin (PPBP), GRO1 (encoding a cytokine also called melanoma growth-stimulatory activity), and IL8 genes can be physically linked. In this study the gamma-interferon induced protein 10 (INP10), bone morphogenetic protein 3 (BMP3), annexin III (ANX3), KIT, amphiregulin (AREG), immunoglobulin J polypeptide (IGJ), deoxycytidine kinase (DCK) and MLLT2 genes were not linked to one another or to the above two groups of genes. Our analysis using somatic cell hybrids combined with previous reports demonstrated that the ADH gene cluster is telomeric to MLLT2 and KIT, ALB, AFP, PF4, beta TG, GRO1, IL8, ANX3, AREG and DCK are centromeric to MLLT2.
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PMID:A mapping study of 13 genes on human chromosome bands 4q11-->q25. 769 25

In Saccharomyces cerevisiae, the alcohol dehydrogenase genes ADH1 and ADH5 are part of a duplicated block of genome, thought to originate from a genome-wide duplication posterior to the divergence from the Kluyveromyces lineage. We report here the characterization of Kluyveromyces marxianus ADH2 and the five genes found in its immediate downstream region, MRPS9, YOL087C, RPB5, RIB7 and SPP381. The order of these six genes reflects the structure of the ancestral S. cerevisiae genome before the duplication that formed the blocks including ADH1 on chromosome XV and ADH5 on chromosome II, indicating these ADH genes share a direct ancestor. On the one hand, the two genes found immediately downstream of KmADH2 are located, for the first, downstream ADH5 and, for the second, downstream ADH1 in S. cerevisiae. On the other hand, the order of the paralogs included in the blocks of ADH1 and ADH5 in S. cerevisiae suggests that two of them have been inverted within one block after its formation, and that inversion is confirmed by the gene order observed in K. marxianus.
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PMID:Kluyveromyces marxianus exhibits an ancestral Saccharomyces cerevisiae genome organization downstream of ADH2. 1097 68

Class III alcohol dehydrogenase is composed of two chi subunits, encoded by the ADH5 gene and existing in all tissues examined. It possesses a great ability to metabolize long-chain alcohols, while its capacity to oxidize ethanol is very limited. The amino-acid sequence homology and identical structural and kinetic properties indicate that class III alcohol dehydrogenase and formaldehyde dehydrogenase are identical enzymes. ADH III plays a significant role in the metabolism of formaldehyde in the human body.
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PMID:[Class III alcohol dehydrogenase and its role in the human body]. 1692 40

Alcohol dependence (AD) is a complex disorder with environmental and genetic origins. The role of two genetic variants in ALDH2 and ADH1B in AD risk has been extensively investigated. This study tested for associations between nine polymorphisms in ALDH2 and 41 in the seven ADH genes, and alcohol-related flushing, alcohol use and dependence symptom scores in 4597 Australian twins. The vast majority (4296) had consumed alcohol in the previous year, with 547 meeting DSM-IIIR criteria for AD. There were study-wide significant associations (P<2.3 x 10(-4)) between ADH1B-Arg48His (rs1229984) and flushing and consumption, but only nominally significant associations (P<0.01) with dependence. Individuals carrying the rs1229984 G-allele (48Arg) reported a lower prevalence of flushing after alcohol (P=8.2 x 10(-7)), consumed alcohol on more occasions (P=2.7 x 10(-6)), had a higher maximum number of alcoholic drinks in a single day (P=2.7 x 10(-6)) and a higher overall alcohol consumption (P=8.9 x 10(-8)) in the previous year than those with the less common A-allele (48His). After controlling for rs1229984, an independent association was observed between rs1042026 (ADH1B) and alcohol intake (P=4.7 x 10(-5)) and suggestive associations (P<0.001) between alcohol consumption phenotypes and rs1693482 (ADH1C), rs1230165 (ADH5) and rs3762894 (ADH4). ALDH2 variation was not associated with flushing or alcohol consumption, but was weakly associated with AD measures. These results bridge the gap between DNA sequence variation and alcohol-related behavior, confirming that the ADH1B-Arg48His polymorphism affects both alcohol-related flushing in Europeans and alcohol intake. The absence of study-wide significant effects on AD results from the low P-value required when testing multiple single nucleotide polymorphisms and phenotypes.
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PMID:Associations of ADH and ALDH2 gene variation with self report alcohol reactions, consumption and dependence: an integrated analysis. 1899 23

Recently, Macgregor et al. (2009) demonstrated significant associations of ADH polymorphisms with reactions to alcohol and alcohol consumption measures in an Australian sample. The aim of the present study was to replicate these findings in a Dutch sample. Survey data on alcohol phenotypes came from 1,754 unrelated individuals registered with the Netherlands Twin Register. SNPs in the ADH gene cluster located on chromosome 4q (n = 491) were subdivided in seven gene sets: ADH5, ADH4, ADH6, ADH1A, ADH1B, ADH1C and ADH7. Within these sets associations of SNPs with alcohol consumption measures, age at onset variables, reactions to alcohol and problem drinking liability were examined. Of the original 38 SNPs studied by Macgregor et al. (2009), six SNPs were not available in our dataset, because one of them had a minor allele frequency < .01 (rs1229984) and five could not be imputed. The remaining SNP associations with alcohol phenotypes as identified by Macgregor et al. (2009) were not replicated in the Dutch sample, after correcting for multiple genotype and phenotype testing. Significant associations were found however, for reactions to alcohol with a SNP in ADH5 (rs6827292, p = .001) and a SNP just upstream of ADH5 (rs6819724, p = .0007) that is in strong LD with rs6827292. Furthermore, an association between age at onset of regular alcohol use and a SNP just upstream of ADH7 (rs2654849, p = .003) was observed. No significant associations were found for alcohol consumption and problem drinking liability. Although these findings do not replicate the earlier findings at the SNP level, the results confirm the role of the ADH gene cluster in alcohol phenotypes.
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PMID:Associations between ADH gene variants and alcohol phenotypes in Dutch adults. 2015 5


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