ADH4

..001) between alcohol consumption phenotypes and rs1693482 (ADH1C), rs1230165 (ADH5) and rs3762894 (ADH4)...

We found strong associations between ADH4 gene variation and alcohol and drug dependence by the Hardy-Weinberg Disequilibrium (HWD) test and case-control association analysis in an initial study...

..The present study examined evidence for the association of alcohol metabolism genes with AD in the Irish Affected Sib Pair Study of alcohol dependence...

..The mechanism by which this allelic effect is mediated is not yet clearly understood. This study examined the effect of ADH2*2 on alcohol-elimination rates (AER) under experimental conditions...

..Strong associations between ADH4 variation and SD have been reported...

..These features and the presence of pi ADH in human liver imply a physiological role for pi ADH in the degradation of circulating epinephrine and norepinephrine...

..SNPs were associated with the early stages of alcohol metabolism, with additional effects in the ADH1A, ADH1B and ADH4 regions...

The authors evaluated the association of three functional promoter polymorphisms of the ADH4 gene with alcohol dependence.

..The ADH4 gene, an important member of this family, is a functional and positional candidate for alcohol dependence...

..However, ADH1, ADH3 and ADH4 predominate in rat skin, demonstrate different sensitivities to pyrazole, and are responsible for metabolising ..

..13 growing on defined medium with xylose or maltose as carbon substrate was carried out using 2-D gel electrophoresis/Maldi-ToF and nano-HPLC MS/MS...

..In addition, the effect of these drugs on the hepatic levels of an aldehyde reductase (AFB1-AR) that metabolizes the cytotoxic dialdehydic form of AFB1 has been studied as this enzyme also ..

..The second objective was to demonstrate the presence of different enzymes transforming vitamin A to retinoic acid and the functionality of this metabolic pathway in the corneal epithelium...

..by 3 alpha-hydroxysteroid dehydrogenase type 2, whereas 1(')-OXPH(4) was produced by aldose reductase, aldehyde reductase, and 20 alpha-hydroxysteroid dehydrogenase, and both 1(')-OXPH(4) and 2(')-OXPH(4) were detected as the ..

..Glucuronate is converted to l-gulonate by aldehyde reductase, an enzyme of the aldo-keto reductase superfamily...

..ADH-1 activity in female ovaries was inhibited less by 2-propanol than ADH-2. These results do not support the hypothesis that 2-propanol acts as a selective factor favoring the Adh-2F allele...

..In addition to GSTA5, we have identified a novel aflatoxin-aldehyde reductase (AFAR) that is similarly induced by ethoxyquin...

..However, it was the same ADH isoenzyme (ADH-3) that oxidized the different glycolethers tested in both male and female rat livers, and the substrate specificity was 2-BE > 2-EE > 2-ME...

..The estimated age of the polymorphism is compatible with this hypothesis, but firmer support could be difficult to obtain...

..Therefore, this inducible enzyme has been designated aflatoxin B1-aldehyde reductase (AFB1-AR)...

b>Adh4, a member of the mouse alcohol dehydrogenase (ADH) gene family, encodes an enzyme that functions in vitro as a retinol dehydrogenase in the conversion of retinol to retinoic acid, an important developmental signaling molecule...

..Finally the class III structure supports evolutionary relationships suggesting that the three classes constitute clearly separate enzymes within the group of mammalian zinc-containing alcohol dehydrogenases...

The ability of class I alcohol dehydrogenase (ADH1) and class IV alcohol dehydrogenase (ADH4) to metabolize retinol to retinoic acid is supported by genetic studies in mice carrying Adh1 or Adh4 gene disruptions...

..Herein, we have used transgenic mice to examine the mouse gene encoding class IV ADH (ADH4), an enzyme that is weakly effective as an ethanol dehydrogenase, but highly effective as a retinol dehydrogenase ..

The human alcohol dehydrogenase 4 gene (ADH4) encodes the human pi-alcohol dehydrogenase (pi-ADH), which can contribute to ethanol metabolism at moderate and high concentrations of ethanol...

Human alcohol dehydrogenase (ADH) constitutes a complex family. Class IV ADH (ADH4) is characteristic in its epithelial expression in the aerodigestive tract and high V(max) and K(m) for oxidation of ethanol...

..Here, Adh1, Adh3, and Adh4 null mutant mice have been examined following acute and chronic vitamin A excess...

..Reporter gene expression following transfection into mouse F9 embryonal carcinoma cells indicated that only Adh-2 possesses promoter activity...

..In contrast, the aldehyde reductase AKR1A1 was not induced by either treatment...

..Although similar formation of DHPG was observed with human liver aldehyde reductase, the production of DHPG was more effective with aldose reductase than aldehyde reductase...

..This urinary detection of the alcohol products directly contributes to the goal of mass balancing the fate of the bioreactive 8,9-epoxides of AFB 1 in vivo...

Rat aflatoxin B(1) aldehyde reductase (called AFAR1 or AKR7A1) is a member of the aldo-keto reductase 7 family, which metabolizes the environmental carcinogen aflatoxin B(1)...

The aldo-keto reductase (AKR) 7 family is composed of the dimeric aflatoxin B(1) aldehyde reductase (AFAR) isoenzymes. In the rat, two AFAR subunits exist, designated rAFAR1 and rAFAR2...

..In addition to aldose reductase, chromatofocusing demonstrated the presence of aldehyde reductase, another NADPH-dependent reductase...

..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...

..to human chlordecone reductase, bovine lung prostaglandin F synthase, human aldose reductase, human aldehyde reductase, and frog lens rho-crystallin, placing rabbit ovarian 20 alpha HSD in the aldo-keto reductase family of ..

..Significant activities of glutathione reductase, aldose reductase (EC.1.1.1.21) and aldehyde reductase (EC.1.1.1.2) were present in islets...

..Aldehyde dehydrogenase and aldehyde reductase activities in both young and old CR mice were unchanged by caloric restriction...

..a gene encoding a protein of 330 amino acids that is 78% identical with the Rattus norvegicus aflatoxin B1 aldehyde reductase (Afar) and, therefore, likely represents its human homologue...

1. Aldose reductase and aldehyde reductase were purified to homogeneity from human testis. 2...

..B 1 (AFB 1) dialdehyde metabolite to its corresponding mono and dialcohols, catalyzed by aflatoxin B 1-aldehyde reductase (AFAR, rat AKR7A1, and human AKR7A3), is greatly increased in livers of rats treated with numerous ..

Mammalian alcohol dehydrogenases ADH1 (class I ADH) and ADH4 (class IV ADH) function as retinol dehydrogenases contributing to the synthesis of retinoic acid, the active form of vitamin A involved in growth and development...

..acid, probably through stepwise transformation catalyzed by monoamine oxidase, aldehyde dehydrogenase and aldehyde reductase. Activity of the melatonin-forming enzyme hydroxyindole-O-methyltransferase was notably below detectable ..

..These results imply that the prevention of protein adducts mediated by AKR are not critical to protection against AFB(1) tumorigenicity...

..gelsolin, phospholipid transfer protein, ATP-binding cassette transporter A8 (ABCA8), androgen-inducible aldehyde reductase, and Na(+)/sulfate cotransporter SUT-1...

..Electronic supplementary material to this paper can be obtained by using the Springer LINK server located at http://dx.doi.org/wo.1007/s00425-002-0834-1...

..This enzyme exhibits relatively broad aldehyde reductase activity and some ketone reductase activity, the activity for aromatic substitutive aldehydes being ..

In contrast with fractions from control animals, an aldehyde reductase, which catalyses the reduction of aflatoxin B1-dihydrodiol, in the dialdehyde form at physiological pH values, to aflatoxin B1-dialcohol, is expressed in cytosolic ..

..proteins present high identities (68-80%) with four Arabidopsis clones and a 67% identity with the aldose/aldehyde reductase from Medicago sativa...

..We speculate that in Escherichia coli YqhD is part of a glutathione-independent, NADPH-dependent response mechanism to lipid peroxidation...

..that bovine lung PGF synthase shows 62% identical plus conservative substitutions compared with human liver aldehyde reductase [Wermuth, B., Omar, A., Forster, A., Francesco, C., Wolf, M., Wartburg, J.P., Bullock, B. & Gabbay, K.H...

..Dual expression of potential biomarkers in both benign and malignant pancreatic tumors was a major obstacle in the development of diagnostic biomarkers of early pancreatic cancer...

..Whereas aldehyde reductase and aldose reductase are AKRs, several forms of carbonyl reductase belong to the SDRs...

..the essential lysine was found to be highly homologous with a segment of the sequence of both human liver aldehyde reductase and rat lens aldose reductase...

..other enzymes, including bovine prostaglandin F synthase, human chlordecone reductase, human aldose reductase, human aldehyde reductase, and frog lens epsilon-crystalline, suggesting that these proteins belong to the same gene family.

..The substrate specificities were in fair agreement with those of carbonyl reductase. However, the partially purified enzyme was strongly inhibited by inhibitors of aldehyde reductase, such as barbital, phenobarbital and sodium valproate.

b>Aldehyde reductase reduces a wide variety of toxic and physiological aldehydes with a marked preference for negatively charged substrates such as glucuronate...

....

..such as bovine prostaglandin F synthase, human chlordecone reductase, human aldose reductase, human aldehyde reductase and frog lens epsilon-crystallin, suggesting that these proteins belong to the same gene family...

Aldo-keto reductase 1a4 (AKR1a4; EC 1.1.1.2) is the mouse orthologue of human aldehyde reductase (AKR1a1), the founding member of the AKR family. As an NADPH-dependent enzyme, AKR1a4 catalyses the conversion of D-glucuronate to L-gulonate...

..This protein, having a sequence similar to that of aldehyde reductase, was up-regulated in myostatin-null mitochondria, but its importance was not established, although it might ..

..SFN, Cuo and Ro increased the expression of xenobiotic enzymes (epoxide hydrolases 1 and 2 and aflatoxin B1 aldehyde reductase) and of the antioxidant enzyme haeme oxygenase regulated by an 'antioxidant response element' (ARE) compared ..

AKR1A1 or aldehyde reductase is a member of the aldo-keto reductases superfamily that is evolutionarily conserved among species...

..Plasmid-borne genes for putative aldehyde dehydrogenases, an aldehyde reductase, and an alcohol oxidoreductase were also induced during growth with dioxane...

..structure of prostaglandin (PG) F synthetase from bovine lung shows 62% similarity with that of human liver aldehyde reductase (EC 1.1.1.2) (Watanabe, K., Fujii, Y., Nakayama, K., Ohkubo, H., Kuramitsu, S., Kagamiyama, H., Nakanishi, S...

..Transposition of Ty elements to two target loci encoding distinct alcohol dehydrogenase enzymes, ADH2 and ADH4, was examined in cells exposed to increasing doses of UV light or 4NQO...

..4 microM) and indicate that at the usual concentration of inhibitor only ADH-3 activity will be effectively suppressed. ADH-1 will be, therefore, responsible in part for the residual ethanol oxidation activity in pyrazole-treated rats...

..These results allow us to assume an important role of rat liver ADH-3 in the mechanism of alcohol addiction...

..glucose-regulated protein (GRP94), heat shock 70 kDa protein 5 (GRP78), heat shock 27 kDa protein 1 (Hsp27), aldehyde reductase 1 (aldose reductase), p47 protein and beta-galactoside-binding lectin (galectin-1)...

..Both functional and sequence variation within and between paralogs suggests that Adh has played an important role in the adaptation of D. mojavensis and D. arizonae to their cactophilic life...

..One isoform of alpha-amylase was overexpressed with both types of tannins. Aldehyde reductase was only identified in saliva of the quebracho group...

..g. placental form of glutathione S-transferase (GST-P), carbonic anhydrase, and aflatoxin B1 aldehyde reductase. Our results show both the usefulness of iTRAQ reagent technology for biomarker prevalidation as well as for ..

Activities of aldehyde dehydrogenase and aldehyde reductase in the liver 1.5-, 12-, and 24-month-old rats were measured after 30-min immobilization...

..production of immobilized green fluorescent protein (GFP) on microbeads and by the production and assay of aldehyde reductase (ALR) enzyme with 4-fold or more activity...

..956 of serous sub-type) and controls (N = 2046) from three studies were genotyped at 11 SNPs in EPHX1, ADH4, ADH1A, NQO2, NAT2, GSTP1, CYP1A1, and NQO1, following an initial SNP screen in a subset of participants...

..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...

..imbalance in ribonucleotide reductase (RNR), which is induced by 5-FOA, and the specific promoter of URA3 fused to ADH4 at telomere VII-L are jointly responsible for the variegated phenotype...

..Oxidative stress-related proteins including Cu/Zn superoxide dismutase, oxidoreductase and aldehyde reductase were also up-regulated...

..Specifically, at 72 hours, queen intended larvae over-expressed transketolase, aldehyde reductase, and enolase proteins which are involved in carbohydrate metabolism and energy production, imaginal disc ..

..N-acetyl-β-glucosaminidase, cauxin, glutathione peroxidase, acidic seminal fluid protein (aSFP), aldehyde reductase, α-l-fucosidase, α-1-β-glycoprotein, apolipoprotein A-1, β actin, calmodulin, cathepsin D, cystatin E/M, ..

..Therefore, we propose that YqhC is a transcriptional activator of YqhD, which acts as an aldehyde reductase with specificity for certain aldehydes, including GO.

....

Human aldehyde reductase is a NADPH-dependent aldo-keto reductase that is closely related (65% identity) to aldose reductase, an enzyme involved in the pathogenesis of some diabetic and galactosemic complications...

..acid example 16, inhibits aldose reductase with an IC50 of 8 nM, while being inactive against aldehyde reductase (IC50>100 microM), a related enzyme involved in the detoxification of reactive aldehydes.

..ADH1 and ADH2 are the major MDR enzymes in liver retinol detoxification, while ADH3 (less active) and ADH4 (most active) participate in RA generation in tissues...

..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 ..

..bioavailability, putative inhibitors should possess a high level of selectivity for ALR2 over the related aldehyde reductase (ALR1)...

..Alcohol abuse is a complex multifactorial disease. It is believed that alcohol dependence is mostly caused by genetic (40-50%) and environmental (50-60%) factors...

..The ectopic expression pattern is dependent on the proximity of at least two sequence elements. Thus, tissue-specific transcription can involve complex proximity-dependent interactions among combinations of regulatory elements...

..The effects of this high variability on the ref(2)P protein are discussed in relation to its specific antiviral properties and to its function in D. melanogaster, where it is required for male fertility...

..To explain this unexpected finding, it is proposed that the ADH: genes of the family Drosophilidae may not be orthologous to the ADH: genes of the other two families, Tephritidae and Sarcophagidae...

..The absence of enzymes to convert ethanol to acetaldehyde, coupled with oocyte expression of the acetaldehyde-degrading enzyme, Ahd-5, may be protective for the early embryo...

..We have found that Ty transposition at the ADH4 and ADH2 loci is not only active, but 50-fold more frequent in meiotic yeast than in mitotic cells...

..In myelocytic leukemia cells, the major reductase was aldehyde reductase, and levels of aldose reductase were extremely low...

..and a growth defect that can be rescued by dietary retinol supplementation, whereas the effect of a loss of ADH1 or ADH4 is noticed only in mice subjected to vitamin A excess or deficiency, respectively...

..the following potencies of AR inhibitors: in vitro activities for AR, in vitro selectivities between AR and aldehyde reductase, their pharmacological effects in vivo, and their effectiveness in clinical trials...

..We have yet to determine whether aldose reductase is the black sheep of the aldehyde reductase family, or whether it is a skeleton in the cupboard, waiting to be clothed in the flesh of new revelations ..

..and dual NADPH/NADH-specific yeast xylose reductases and across two aldo/keto reductase families in spite of the phylogenetic separation of the host organisms producing xylose reductase (family 2B) and aldehyde reductase (family 1A).

..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...

..the former a new member of the rat aldo-keto reductase superfamily that is closely related to aflatoxin, B1 aldehyde reductase has been identified...

..sixteen functional and/or non-synonymous variants in the class I and II alcohol dehydrogenase genes (ADH1B, ADH1C, ADH4), the aldehyde dehydrogenase genes (ALDH1, ALDH2) and the cytochrome P4502E1 gene (CYP2E1), all of which are ..

..metabolized primarily to an acid via mitochondrial aldehyde dehydrogenase (ALDH2) but also to an alcohol by aldehyde reductase (ALR). Recent work implicates oxidative stress and lipid peroxidation products, e.g...

..Recently it was shown that ethoxyquin and antiobiotic tunicamycin also induce aldehyde reductase, another member of the aldo-keto reductase family...

..alcohol-induced liver damage Distal cis-linked sequence in a BAC clone will direct expression of Adh1 in liver and Adh4 in stomach No sequence directing liver expression of any human class I ADH gene is known...

..Project # 1 (Dr. Penning) will compare the roles of human aldehyde reductase (AKR1A1), CYP1A1/CYP1B1, and CYP-peroxidase in the metabolic activation of PAH using a stable expression ..

..Our studies show that in the heart enals are metabolized by aldose reductase (AR), aldehyde reductase, and glutathione-S-transferases...

..Our studies show that in the heart enals are metabolized by aldose reductase (AR), aldehyde reductase, and glutathione-S-transferases...

..The activities of aldehyde reductase, aldose reductase, dihydrodiol dehydrogenase and glyoxalase I will be assessed in primary Muller cells...

..probe time-averaged and time-dependent electric fields in several enzymes: human aldose reductase and human aldehyde reductase (Sub-Aim 1A), both important to the control of diabetes, and ketosteroid isomerase (Sub-Aim 1B)...

..probe time-averaged and time-dependent electric fields in several enzymes: human aldose reductase and human aldehyde reductase (Sub-Aim 1A), both important to the control of diabetes, and ketosteroid isomerase (Sub-Aim 1B)...

..In addition, all the ARIs presently known inhibit both AR and aldehyde reductase, and both enzymes have overlapping substrate specificities...

..One key to finding strong inhibitors of hALR2 that do not also bind to a structurally similar protein, human aldehyde reductase (hALR1), is to measure the electrostatic field of the inhibitor binding site...

..The results of this study will expand upon promising data from pilot studies performed in this laboratory on acute 1,4-BD and GHB toxicity as well as novel therapeutic agents for its potential medical management. ..

..B6 mice are naturally hypomorphic for alcohol dehydrogenase 4 (Adh4), which may be involved in detoxifying vitamin A metabolites resulting in these enzyme expression ..

..NHS cohorts, he will evaluate the associations of PD risk with common polymorphisms of NAT2, CYP1A2, ADH2, ADH3, ADH4, and MTHFR...

..ADH3 and promoters of ADH4 and ALDH2 will also be studied. Psychiatric comorbidity, religiosity and trauma will be assessed and controlled...

DESCRIPTION (Adapted from applicant's abstract): Aldose and aldehyde reductase are closely related members of the aldo-keto reductase superfamily...

..Also, we will identify the novel RA-generating enzymes expressed in the neural tube and heart and begin genetic studies on them. ..

..3) Prepare and ALDH-I knockout mouse plus mice mutated for one or more ADHs and ALDH-I, then analyze their phenotype as above. ..