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

Saccharomyces cerevisiae is the main microorganism used in wine brewing, because this microbe has potent ability to produce alcohol dehydrogenase. We have recently discovered that some genera of mushroom produced alcohol dehydrogenase, and made wine by using a mushroom in place of S. cerevisiae. The highest alcohol concentration in this wine was achieved with Pleurotus ostreatus (2.6 M, 12.2%). In the case of Agaricus blazei, the same alcohol concentration (1.7 M, 8%) was produced under both aerobic and anaerobic conditions. This wine produced by A. blazei contained about 0.68% beta-D-glucan, which is known to have a preventive effects against cancer. The wine made by using Flammulina velutipes showed thrombosis-preventing activity, giving a prolonged thrombin clotting time 2.2-fold that of the control. Thus, the wine made by using mushroom seems to be a functional food which can be expected to have preventive effects against cancer and thrombosis.
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PMID:Characteristics of wine produced by mushroom fermentation. 1151 44

Enzymes involved in various protective and metabolic processes of carbonyl compounds were analysed utilising a micro-array method in a three-stage in vitro model for oral carcinogenesis involving cultured normal, immortalised and malignant human oral keratinocytes. A complete transcript profiling of identified carbonyl-metabolising enzymes belonging to the ADH, ALDH, SDR and AKR families is presented. Expression of 17 transcripts was detected in normal, 14 in immortalized and 19 in malignant keratinocytes of a total of 12,500 genes spotted on the micro-array chip. For the detected transcripts, about half were changed by cell transformation, and for the various enzyme families, differences in expression patterns were observed. The detected AKR transcripts displayed a conserved pattern of expression, indicating a requirement for the keratinocyte phenotype, while most of the detected SDRs displayed changed expression at the various stages of malignancy. The importance of multiple experiments in using a microarray technique for reliable results is underlined and, finally, the strength of the method in detecting co-expressed enzymes in metabolic pathways is exemplified by the detection of the formaldehyde-scavenging pathway enzymes and the polyol pathway enzymes.
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PMID:Micro-array chip analysis of carbonyl-metabolising enzymes in normal, immortalised and malignant human oral keratinocytes. 1170 98

Curcumin, the yellow pigment in turmeric, prevents malignancies in the intestinal tract of rodents. It is under clinical evaluation as a potential colon cancer chemopreventive agent. The systemic bioavailability of curcumin is low, perhaps attributable, at least in part, to metabolism. Indirect evidence suggests that curcumin is metabolized in the intestinal tract. To investigate this notion further, we explored curcumin metabolism in subcellular fractions of human and rat intestinal tissue, compared it with metabolism in the corresponding hepatic fractions, and studied curcumin metabolism in situ in intact rat intestinal sacs. Analysis by high-performance liquid chromatography, with detection at 420 or 280 nm, permitted characterization of curcumin conjugates and reduction products. Chromatographic inferences were corroborated by mass spectrometry. Curcumin glucuronide was identified in intestinal and hepatic microsomes, and curcumin sulfate, tetrahydrocurcumin, and hexahydrocurcumin were found as curcumin metabolites in intestinal and hepatic cytosol from humans and rats. The extent of curcumin conjugation was much greater in intestinal fractions from humans than in those from rats, whereas curcumin conjugation was less extensive in hepatic fractions from humans than in those from rats. The curcumin-reducing ability of cytosol from human intestinal and liver tissue exceeded that observed with the corresponding rat tissue by factors of 18 and 5, respectively. Curcumin sulfate was identified in incubations of curcumin with intact rat gut sacs. Curcumin was sulfated by human phenol sulfotransferase isoenzymes SULT1A1 and SULT1A3. Equine alcohol dehydrogenase catalyzed the reduction of curcumin to hexahydrocurcumin. The results show that curcumin undergoes extensive metabolic conjugation and reduction in the gastrointestinal tract and that there is more metabolism in human than in rat intestinal tissue. The pharmacological implications of the intestinal metabolism of curcumin should be taken into account in the design of future chemoprevention trials of this dietary constituent.
Cancer Epidemiol Biomarkers Prev 2002 Jan
PMID:Metabolism of the cancer chemopreventive agent curcumin in human and rat intestine. 1181 7

Epidemiology has demonstrated that alcoholic beverages are causally related to oropharyngolaryngeal, esophageal, liver, colorectal, and female breast cancer. Among Japanese male alcoholics screened by endoscopy combined with esophageal iodine staining and immunofecal occult blood tests, 4.2% had esophageal squamous cell carcinoma (SCC); 1.2%, oropharyngolaryngeal SCC; 1.4%, stomach adenocarcinoma; 1.9%, colorectal adenocarcinoma. The inactive form of aldehyde dehydrogenase-2 (ALDH2), encoded by the gene ALDH2*1/2*2, which is prevalent in Asians, exposes them to higher levels of acetaldehyde after drinking and was a strong risk factor for these cancers among Japanese heavy drinkers. Inactive ALDH2 was also associated with synchronous and metachronous multiple esophageal cancers. These results suggest a general role of acetaldehyde, an established animal carcinogen, in carcinogenesis of the human alimentary tract. The oropharyngolarynx and esophagus lack ALDH2 activity, suggesting that after exposure to acetaldehyde derived from systemic, mucosal, salivary, or bacterial production or alcoholic beverages, these organs' inefficient degradation of acetaldehyde enhances the chances for local acetaldehyde-associated carcinogenesis. The normal alcohol dehydrogenase-2 (ADH2), encoded by ADH2*1/2*1, is another risk factor for oropharyngolaryngeal and esophageal cancer in Japanese alcoholics. For patients with both normal ADH2 and inactive ALDH2, the risks for oropharyngolaryngeal and esophageal cancer are enhanced in a multiplicative fashion. The responses to a simple questionnaire about both current and past facial flushing after drinking a glass of beer can indicate an individual's ALDH2 phenotype fairly well. Use of this questionnaire to obtain information on ALDH2-associated cancer susceptibility could contribute to the prevention of alcohol-related cancer in Asians.
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PMID:[Alcohol and oropharyngolaryngeal and digestive tract cancer]. 1182 13

Aldose reductase (ALR2) is a target enzyme for the treatment of diabetic complications. Owing to the limited number of currently available drugs for the treatment of diabetic complications, the discovery of new inhibitors of ALR2 that can potentially be optimized as drugs appears highly desirable. In this study, a molecular docking analysis of the structures of more than 127,000 organic compounds contained in the National Cancer Institute database was performed to find and score molecules that are complementary to ALR2. Besides retrieving several carboxylic acid derivatives, which are known to generally inhibit aldose reductase, docking proposed other families of putative inhibitors such as sulfonic acids, nitro-derivatives, sulfonamides and carbonyl derivatives. Twenty-five compounds, chosen as the highest-scoring representatives of each of these families, were tested as aldose reductase inhibitors. Five of them were found to inhibit aldose reductase in the micromolar range. For these active compounds, selectivity with respect to the closely-related aldehyde reductase was determined by measuring the corresponding inhibitory activities. The structures of the complexes between the new lead inhibitors and aldose reductase, here refined with molecular mechanics and molecular dynamics calculations, suggest that new pharmacophoric groups can bind aldose reductase very efficiently. In the case of the family of the nitro-derivative inhibitors, a class of particularly interesting compounds, a round of optimizations was performed with the synthesis and biological evaluation of a series of derivatives aimed at testing the proposed binding mode and at improving interaction with active site residues. Starting from a hit compound having an IC(50) of 42 microM, the most potent compound synthesized showed a 10-fold increase in inhibitory activity and 10-fold selectivity with respect to ALR1, and structure--activity relationships of the designed compounds were in agreement with the proposed mode of binding at the active site.
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PMID:Discovery of new inhibitors of aldose reductase from molecular docking and database screening. 1188 6

Molecular genetic studies have indicated that alcohol dehydrogenase may be involved in the synthesis of retinoic acid, a hormonal molecule regulating diverse cellular functions at the transcriptional level. Class IV alcohol dehydrogenase (ADH) has been reported to be the most efficient enzyme catalyzing oxidation of retinol in human ADH family. Initial velocity, product inhibition, and dead-end inhibition experiments were performed with the recombinant human class IV ADH to elucidate kinetic mechanism with all-trans-retinol and all-trans-retinal as natural substrates. Fluorescence quenching was titrated in formation of the binary and abortive ternary enzyme complexes. The minimal mechanism deduced from steady-state kinetic and equilibrium binding studies is best described as an asymmetric rapid equilibrium random mechanism with two dead-end ternary complexes for retinol oxidation and a rapid equilibrium ordered mechanism with one dead-end ternary complex for retinal reduction, a unique mechanistic form for zinc-containing ADHs in the medium chain dehydrogenase/reductase superfamily. Dissociation constants for the binary complexes as well as the productive and abortive ternary complexes determined from different experimental approaches are in reasonable agreement. Kinetic isotope effect studies suggest rate-limiting isomerization of the central ternary complexes in both reaction directions. The potential interference of retinol metabolism by ethanol through the ADH pathway may play a significant role in the pathogenesis of fetal alcohol syndrome and alcohol-related upper digestive tract cancer.
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PMID:Kinetic mechanism of human class IV alcohol dehydrogenase functioning as retinol dehydrogenase. 1199 93

Progesterone receptor (PR) mediates the effects of progesterone in mammary tissues and plays a crucial role in normal breast development and in breast cancer. PR proteins are expressed as two isoforms, PRA and PRB, that have different capacities to activate target genes, yet it is unknown whether progesterone action in normal and malignant breast is mediated by PRA and/or PRB. This study determines the relative expression of PRA and PRB in normal breast and in benign, premalignant and malignant archival breast lesions by dual immunofluorescent histochemistry. In normal breast and in proliferative disease without atypia (PDWA) PRA and PRB were co-expressed within the same cells in comparable amounts, implicating both isoforms in progesterone action. In atypical lesions, however, there was a significant increase in predominant expression of PRA or PRB, with lesion progression from the normal state to malignancy. PR isoform predominance, especially PRA predominance, was evident in a high proportion of ductal carcinomas in situ (DCIS) and invasive breast lesions. In the normal breast and in PDWA, the relative expression of PRA and PRB in adjacent cells was homogenous. There was a significant increase in cell-to-cell heterogeneity of PR isoform expression in ADH and DCIS lesions and in the majority of breast cancers. Heterogeneous cell-to-cell expression of PR isoforms occurred prior to overall predominant expression of one isoform in premalignant breast lesions, demonstrating that loss of control of relative PRA:PRB expression is an early event in the development of breast cancer. PRA:PRB ratios within a breast lesion are likely to be important as both markers and effectors of tumor growth and development, and progressively aberrant PR isoform expression may play a role in the etiology of breast cancer.
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PMID:Loss of co-ordinate expression of progesterone receptors A and B is an early event in breast carcinogenesis. 1203 7

MaeIII Restriction Fragment Length Polymorphism in exon 3 of the alcohol dehydrogenase II was assessed in serum from 467 randomly selected German women and 278 women with invasive breast cancer to evaluate the interaction between a polymorphism of the alcohol dehydrogenase II gene, alcohol consumption and risk for breast cancer. In both groups, usual consumption of different alcoholic beverages was asked for using semiquantitative food frequency questionnaires. We used multivariable logistic regression to separately estimate the association between alcohol consumption and alcohol dehydrogenase II polymorphism in the population sample and women with breast cancer. The alcohol dehydrogenase II polymorphism was detected in 14 women from the population sample (3.0%) and in 27 women with invasive breast cancer (9.7%). Frequency of alcohol consumption was independent of the genotype in the population sample. In women with breast cancer, there was a significant inverse association between the alcohol dehydrogenase II polymorphism and frequency of alcohol consumption (adjusted case-only odds ratio over increasing frequency of alcohol consumption=0.5; P for interaction=0.02). We observed a gene-environment interaction between the alcohol dehydrogenase II polymorphism, alcohol consumption, and risk for breast cancer. Breast cancer risk associated with alcohol consumption may vary according to the alcohol dehydrogenase II polymorphism, probably due to differences in alcohol metabolism.
Br J Cancer 2002 Aug 27
PMID:Interaction between alcohol dehydrogenase II gene, alcohol consumption, and risk for breast cancer. 1218 49

Carcinogenicity of 1,3-butadiene (BD) has been linked to its metabolic activation of genotoxic epoxides. The inherited variations in the activity of BD-metabolizing enzymes may be responsible for individual differences that modulate the effects of BD exposure. In this study, 40 Italian subjects (30 BD-exposed workers and 10 clerks) were investigated to evaluate the role of genetic polymorphism of cytochromes P450 2E1, microsomal epoxide hydrolase, glutathione transferases GSTM1, GSTP1, GSTT1, and alcohol dehydrogenase, on urinary N-acetyl-S-(3,4-hydroxybutyl)-L-cysteine (MI) and hemoglobin N-(2,3,4-trihydroxybutyl)-valine adducts (THBVal). Median urinary MI and THBVal levels were 1.71 mg/g creatinine and 37.0 pmol/g globin in BD-exposed workers (exposure range, 4-201 microg/m(3)) and 1.42 mg/g creatinine and 35.3 pmol/g globin in unexposed subjects. No difference between the two groups was observed. Among all subjects, MI and THBVal levels were significantly correlated (r = 0.333). Smoking positively influenced the formation of THBVal. Higher THBVal levels were found in subjects with GSTM1 null and GSTT1 null genotypes; borderline influences were also noticed for CYP2E1(G(-35)T). An additive effect of combined polymorphisms for CYP2E1, GSTM1, and GSTT1 genes on the THBVal levels was suggested. A multiple linear regression analysis, where each factor contributed significantly, correlated THBVal levels with smoking, CYP2E1(G(-35)T), GSTT1, and GSTM1 genotypes (r = 0.698). Our results indicate that the THBVal level is influenced by genotypes, and that the analysis of combined polymorphisms may be the key to a better understanding of the role played by polymorphism of BD-metabolizing enzymes.
Cancer Epidemiol Biomarkers Prev 2002 Oct
PMID:Influence of metabolic genotypes on biomarkers of exposure to 1,3-butadiene in humans. 1237 11

The genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2), alcohol dehydrogenase-2 (ADH2), ADH3, and glutathione S-transferase M1 (GSTM1) influence the metabolism of alcohol and other carcinogens. The ALDH2*1/2*2 genotype, which encodes inactive ALDH2, and ADH2*1/2*1, which encodes the low-activity form of ADH2, enhance the risk for esophageal cancer in East Asian alcoholics. This case-control study of whether the enzyme-related vulnerability for esophageal cancer can be extended to a general population involved 234 Japanese men with esophageal squamous cell carcinoma and 634 cancer-free Japanese men who received annual health checkups. The GSTM1 genotype was not associated with the risk for this cancer. Light drinkers (1-8.9 units/week) with ALDH2*1/2*2 had an esophageal cancer risk 5.82 times that of light drinkers with ALDH2*1/2*1 (reference category), and their risk was similar to that of moderate drinkers (9-17.9 units/week) with ALDH2*1/2*1 (odds ratio = 5.58). The risk for moderate drinkers with ALDH2*1/2*2 (OR = 55.84) exceeded that for heavy drinkers (18+ units/week) with ALDH2*1/2*1 (OR = 10.38). Similar increased risks were observed for those with ADH2*1/2*1. A multiple logistic model including ALDH2, ADH2, and ADH3 genotypes showed that the ADH3 genotype does not significantly affect the risk for esophageal cancer. For individuals with both ALDH2*1/2*2 and ADH2*1/2*1, the risk of esophageal cancer was enhanced in a multiplicative fashion (OR = 30.12), whereas for those with either ALDH2*1/2*2 or ADH2*1/2*1 alone the ORs were 7.36 and 4.11. In comparison with the estimated population-attributable risks for preference for strong alcoholic beverages (30.7%), smoking (53.6%) and for lower intake of green and yellow vegetables (25.7%) and fruit (37.6%), an extraordinarily high proportion of the excessive risk for esophageal cancer in the Japanese males can be attributed to drinking (90.9%), particularly drinking by persons with inactive heterozygous ALDH2 (68.5%). Education regarding these risky conditions in connection with ALDH2 and ADH2 is vitally important in a new strategic approach aimed at preventing esophageal cancer in East Asians.
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PMID:Genetic polymorphisms of alcohol and aldehyde dehydrogenases and glutathione S-transferase M1 and drinking, smoking, and diet in Japanese men with esophageal squamous cell carcinoma. 1241 33


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