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

---

Query: EC:1.1.1.1 (alcohol dehydrogenase)
9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyacrylamide gel-isoelectric focusing (PAGE-IEF) methods were used to examine the multiplicity, tissue distribution, and biochemical genetics of alcohol dehydrogenase (ADH) isozymes among gray short-tailed opossums (Monodelphis domestica). Seven ADH isozymes were resolved and distinguished on the basis of their isoelectric points, tissue distributions, and substrate and inhibitor specificities. ADH1 and ADH2 exhibited Class I properties and were observed in liver (and intestine) extracts. ADH3, ADH4, and ADH5 showed "high-Km" (possibly Class IV) properties, with ADH3 and ADH4 exhibiting high activity in cornea, ear, stomach, and esophagus extracts. ADH6 and ADH7 exhibited Class III properties, including activities as formaldehyde dehydrogenases, with each showing different tissue distribution characteristics; ADH6 was widely distributed, and ADH7 was restricted to prostate extracts. An additional form of formaldehyde dehydrogenase (FDH) was observed, which was inactive with hexenol and ethanol as substrates. Isoelectric point variants were observed for ADH3 (three forms) and for ADH4 (two forms), and the inheritance of ADH3 was studied in 15 families of M. domestica. The data were consistent with codominant inheritance of two alleles (ADH3*A and ADH3*B) at a single autosomal locus (designated ADH3) and with a model involving a dimeric ADH isozyme: ADH3 (gamma 2 isozyme, forming three dimers designated gamma 1(2), gamma 1 gamma 2, and gamma 2(2) in heterozygous individuals).
...
PMID:Biochemical genetics of alcohol dehydrogenase isozymes in the gray short-tailed opossum (Monodelphis domestica). 161 78

Two formaldehyde-induced mutations at the Drosophila Adh locus (Adhfn45 and Adhfn46) were analyzed by determining RNA structures at different developmental stages, polymerase chain reaction (PCR) amplification of the affected genomic regions, and direct sequencing of the resulting double-stranded DNA fragments. Adhfn46 adults and larvae accumulate abundant ADH-like distal (adult) and proximal (larval) transcripts that are shorter than transcripts in wild-type flies by a lesion located in the second ADH protein-coding exon. Direct sequencing of the amplified DNA region showed that Adhfn46 contains a 69-bp in-frame deletion that removes 23 amino acids near one border of the second exon. Consistent with these findings, we observed a shorter ADHfn46 protein present at only 3% of wild-type levels. In contrast, Adhfn45 adults and larvae accumulate much smaller amounts of ADH-like distal and proximal transcripts. Both RNAs have an identical aberration in RNA splicing of the 65-base intron sequence. Direct sequencing of the amplified mutated DNA region showed that Adhfn45 contains a 21-bp deletion that removed and rearranged DNA at the 5' splice junction of the 65-bp intron. No ADH cross-reacting material is detected in Adhfn45 flies. Direct-repeat sequences (3-11 bp) are present flanking and within the mutated DNA regions. The patterns of DNA deletion and deletion accompanied by sequence addition at the mutant sites suggest a slipped mispairing mechanism during DNA replication or repair that involves local DNA homology.
...
PMID:Analysis of formaldehyde-induced Adh mutations in Drosophila by RNA structure mapping and direct sequencing of PCR-amplified genomic DNA. 170 21

Human liver class III alcohol dehydrogenase (chi chi-ADH) and glutathione dependent formaldehyde dehydrogenase are the same enzyme. The enzyme, chi chi-ADH, exhibits a kcat of 200 min-1 and a km of 4 microM for the oxidation of formaldehyde, but only in the presence of GSH. In the absence of GSH the enzyme is essentially inactive toward formaldehyde but very active toward long chain alcohols. Thus, as in the rat (Koivusalo, M., Baumann, M., and Uotila, L. (1989) FEBS Letters 257, 105-109), the class III alcohol dehydrogenase and the GSH dependent formaldehyde dehydrogenase are identical enzymes. S-Hydroxymethyl derivatives of 8-thiooctanoate and lipoate are also very active substrates. The activity is specific for class III alcohol dehydrogenase; neither the class I and II nor the horse EE, ES, and SS isozymes oxidize hemithiolacetals. o-Phenanthroline competitively inhibits both activities and the two substrate types compete with each other.
...
PMID:Human liver class III alcohol and glutathione dependent formaldehyde dehydrogenase are the same enzyme. 187 53

The movement of blood formaldehyde in rabbits that were intoxicated with methanol has been investigated by simple headspace gas chromatography-mass spectrometry for the microdetermination of formaldehyde in the blood. When methanol alone was administered to rabbits orally, formaldehyde could not be detected in the blood. Further, in an experiment on the metabolism of methanol in vitro, formaldehyde was not detected in specimen samples but formate was. In contrast, when methanol was orally administered to rabbits that had been pretreated with diethyldithiocarbamate (DDC), an aldehyde dehydrogenase (ALDH) inhibitor, 17 to 33 microM of formaldehyde were detected in the blood 4 hours later. However, formaldehyde was not detected in the blood when methanol was orally administered to rabbits that had been pretreated with pyrazole, an alcohol dehydrogenase (ADH) inhibitor. After rabbits were given an intravenous administration of formaldehyde, and on the addition of formaldehyde to a rabbit liver homogenate and blood, the formaldehyde in both instances was metabolized rapidly. Formaldehyde that was not metabolized within 10 to 15 minutes, however, bound to the tissue proteins. Therefore, according to the results of this study, formaldehyde was seen to be rapidly metabolized to formate without accumulating in the blood or binding to the tissue proteins. Formaldehyde thus appears to have little influence on the symptoms of methanol poisoning.
...
PMID:The movement of blood formaldehyde in methanol intoxication. II. The movement of blood formaldehyde and its metabolism in the rabbit. 223 29

Three different dehydrogenases able to oxidize formaldehyde were found in the Gram-positive methylotroph, Nocardia sp. 239: an NAD-dependent aldehyde dehydrogenase (NA-ADH), and NAD- and factor-dependent formaldehyde dehydrogenase (FD-FDH), and a dye-linked aldehyde dehydrogenase (DL-ADH). The ratio of the activities observed for the two NAD-linked enzymes varied with growth conditions: batch-wise grown cells had nearly the same activities for both enzymes; in fed batch-wise grown cells (methanol limitation) only FD-FDH was detected. The latter is clearly involved in formaldehyde oxidation, since the enzyme and the factor were found only in methanol-grown cells and the enzyme is specific for formaldehyde. In contrast, the two aldehyde dehydrogenases may have significance for aldehyde dissimilation in general, since both activities could also be demonstrated in ethanol-grown cells (but not in glucose-grown cells) and higher aldehydes are even better substrates than formaldehyde. NA-ADH was purified to homogeneity. The enzyme seems to be a homotetramer since it showed a relative molecular mass of 200,000 and the denaturated form of 55,000. Other characteristics are as follows: the enzyme showed substrate inhibition for the aldehydes tested; optimal activity was found at pH 9.2; the reverse reaction was not observed; the enzyme was specific for NAD; GSH, K+, or NH4+ addition did not stimulate formaldehyde oxidation; the order of NAD and substrate addition to the enzyme was not important; several compounds able to block SH groups were inhibitory. Comparison with NAD-linked aldehyde dehydrogenases from Gram-negative bacteria showed that the Nocardia enzyme is distinct from the enzyme of Pseudomonas putida (EC 1.2.1.46) and of Hyphomicrobium X.
...
PMID:Different types of formaldehyde-oxidizing dehydrogenases in Nocardia species 239: purification and characterization of an NAD-dependent aldehyde dehydrogenase. 224 Nov 49

Vinyl acetate is subject to microbial degradation in the environment and by pure cultures. It was hydrolyzed by samples of soil, sludge, and sewage at rates of up to 6.38 and 1 mmol/h per g (dry weight) under aerobic and anaerobic conditions, respectively. Four yeasts and thirteen bacteria that feed aerobically on vinyl acetate were isolated. The pathway of vinyl acetate degradation was studied in bacterium V2. Vinyl acetate was degraded to acetate as follows: vinyl acetate + NAD(P)+----2 acetate + NAD(P)H + H+. The acetate was then converted to acetyl coenzyme A and oxidized through the tricarboxylic acid cycle and the glyoxylate bypass. The key enzyme of the pathway is vinyl acetate esterase, which hydrolyzed the ester to acetate and vinyl alcohol. The latter isomerized spontaneously to acetaldehyde and was then converted to acetate. The acetaldehyde was disproportionated into ethanol and acetate. The enzymes involved in the metabolism of vinyl acetate were studied in extracts. Vinyl acetate esterase (Km = 6.13 mM) was also active with indoxyl acetate (Km = 0.98 mM), providing the basis for a convenient spectrophotometric test. Substrates of aldehyde dehydrogenase were formaldehyde, acetaldehyde, propionaldehyde, and butyraldehyde. The enzyme was equally active with NAD+ or NADP+. Alcohol dehydrogenase was active with ethanol (Km = 0.24 mM), 1-propanol (Km = 0.34 mM), and 1-butanol (Km = 0.16 mM) and was linked to NAD+. The molecular sizes of aldehyde dehydrogenase and alcohol dehydrogenase were 145 and 215 kilodaltons, respectively.
...
PMID:Degradation of vinyl acetate by soil, sewage, sludge, and the newly isolated aerobic bacterium V2. 228 14

Adhfn23 and Adhfn24 are two formaldehyde-induced, homozygous-viable, alcohol dehydrogenase-null mutants that bear lesions in the gene that codes for the alcohol dehydrogenase (ADH; EC 1.1.1.1) of Drosophila melanogaster. Adhfn23 contains a 34-base pair deletion in the C-terminal coding region of the alcohol dehydrogenase structural gene. By immunological and molecular analysis, we show that the deletion shifts the translation reading frame and results in a prematurely truncated polypeptide product (10 amino acids shorter than wild type) that cross-reacts with antibody raised against ADH. The steady-state level of alcohol dehydrogenase mRNA present in this mutant is close (97%) to that in the wild type, but the steady-state level of alcohol dehydrogenase-like protein is 50% lower. Moreover, the rate of alcohol dehydrogenase synthesis in Adhfn23 flies is reduced to 60% of that found in the wild type. Hence both the rate of synthesis and the rate of degradation of alcohol dehydrogenase are affected. In contrast, Adhfn24 which contains an 11-base pair deletion in the N-terminal coding region of the ADH gene, synthesizes no immunodetectable protein, and the amount of alcohol dehydrogenase mRNA is less than half that of wild-type flies. As with Adhfn23, the deletion in Adhfn24 results in a change in the reading frame. Unlike Adhfn23, however, nucleic acid sequence data indicate that polypeptide chain elongation can proceed for a considerable distance (over 130 amino acids) beyond the deletion. Based upon antigenic binding-site predictions, the resultant aberrant protein (projected 195 amino acids in length) would share few antigenic sites with the alcohol dehydrogenase from the wild type, which may account for the lack of immunoprecipitable material in this mutant. The contrasting effects these two deletions have on the Drosophila ADH mRNA levels and ADH protein levels are discussed.
...
PMID:Molecular consequences of two formaldehyde-induced mutations in the alcohol dehydrogenase gene of Drosophila melanogaster. 244 61

The interdisciplinary evaluation of risks from carcinogens utilizes, inter alia, data on the activities of the compounds in short-term assays. A systematic approach is being used to determine mutagenesis in bacteria (the study of direct activities and specific modes of metabolic activation), DNA damage within primary mammalian cells (DNA single-strand breaks and persistence of damage, by a method extendable to the in vivo situation) and amplified DNA sequences in cultured cells (as an endpoint probably relevant to carcinogenesis). This test combination was expected to reduce some of the shortcomings of other batteries of tests, which suffer from a lack of appropriate metabolic conversion of compounds, irrelevancy of genetic endpoints and pharmacokinetic limitations. Furthermore, as each assay in the test strategy differs from the others only by one of the parameters described above, a reasonable understanding of divergent test results from assay to assay was anticipated. Several substances were investigated to elucidate why their activities in short-term assays and in carcinogenesis experiments do not correlate. The substances were N-nitrodimethylamine, for which formaldehyde is the reactive intermediate in bacterial mutagenesis but not in mammalian cells or in vivo, N-nitrosodiethanolamine, a carcinogen that must be activated by external alcohol dehydrogenase to be mutagenic in bacteria, N-nitrosodialkylamines, with unique organotropism in vivo for which organ-specific activation was studied in vitro, N-nitroso compounds that are inactivated in vivo but not in vitro, and components of the aristolochic acid mixture which may be metabolized oxidatively or reductively, as well as numerous miscellaneous compounds that were expected to be genotoxins on account of their chemical structure. In addition to the assessment of genotoxicity, the results obtained in individual tests of this strategy yield important data on mechanisms of activity, such as organ-specific activation and deactivation, species variations, in vitro/in vivo correlation and persistence or repair of damage.
...
PMID:Detection of mutations in bacteria and of DNA damage and amplified DNA sequences in mammalian cells as a systematic test strategy for elucidating biological activities of chemical carcinogens. 353 93

Methanol and ethylene glycol poisonings share many characteristics both clinically and biochemically. Both alcohols are metabolised via alcohol dehydrogenase to their toxic metabolites. Methanol is slowly metabolised to formaldehyde which is rapidly metabolised to formate, the metabolite mainly responsible for methanol toxicity. Formate metabolism depends upon the folate pool which is small in primates compared with other animals. Therefore, formate accumulates in primates during methanol intoxication and is mainly responsible for the metabolic acidosis in the early stage of intoxication. In late stages lactate may also accumulate, mainly due to formate inhibition of the respiratory chain. This tissue hypoxia caused by formate may explain the ocular as well as the general toxicity. Ethylene glycol is metabolised more rapidly than methanol, via alcohol dehydrogenase to glycolaldehyde which is rapidly metabolised to glycolate, the metabolite mainly responsible for the metabolic acidosis in ethylene glycol poisoning. Glycolate is metabolised by various pathways, including one to oxalate which rapidly precipitates with calcium in various tissues and in the urine. Ethylene glycol toxicity is complex and not fully understood, but is mainly due to the severe metabolic acidosis caused by glycolate and to the calcium oxalate precipitation. The clinical course in both poisonings is initially characterised by the development of metabolic acidosis following a latent period, which is more pronounced in methanol poisoning and is the time taken for both alcohols to be metabolised to their toxic metabolites. In methanol poisoning there are usually visual symptoms progressing to visual impairment, whereas ethylene glycol victims develop renal and cardiopulmonary failure. Prognosis is excellent in both poisonings provided that there is early treatment with alkali to combat acidosis, ethanol as an antimetabolite, and haemodialysis to remove the alcohols and their toxic metabolites. Ethanol is also metabolised by alcohol dehydrogenase, but has a much higher affinity for this enzyme than methanol and ethylene glycol. Presence of ethanol will therefore inhibit formation of toxic metabolites from methanol and ethylene glycol. Due to competition for the enzyme, the therapeutic ethanol concentration depends on the concentration of the other two alcohols, but a therapeutic ethanol concentration around 22 mmol/L (100 mg/dl) is generally recommended. Most patients are, however, admitted at a late stage to hospitals not capable of performing analyses of these alcohols or their specific metabolites on a 24-hour basis.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Methanol and ethylene glycol poisonings. Mechanism of toxicity, clinical course, diagnosis and treatment. 353 23

This paper reports the elimination half-life of methanol in human volunteers. Experiments were made during the morning after the subjects had consumed 1000-1500 ml red wine (9.5% w/v ethanol, 100 mg/l methanol) the previous evening. The washout of methanol from the body coincided with the onset of hangover. The concentrations of ethanol and methanol in blood were determined indirectly by analysis of end-expired alveolar air. In the morning when blood-ethanol dropped below the Km of liver alcohol dehydrogenase (ADH) of about 100 mg/l (2.2 mM), the disappearance half-life of ethanol was 21, 22, 18 and 15 min. in 4 test subjects respectively. The corresponding elimination half-lives of methanol were 213, 110, 133 and 142 min. in these same individuals. The experimental design outlined in this paper can be used to obtain useful data on elimination kinetics of methanol in human volunteers without undue ethical limitations. Circumstantial evidence is presented to link methanol or its toxic metabolic products, formaldehyde and formic acid, with the pathogenesis of hangover.
...
PMID:Elimination half-life of methanol during hangover. 358 16


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---