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)

Four isoenzymes of aldehyde dehydrogenase were partially purified from rat liver mitochondria by hydroxylapatite chromatography and gel filtration. While three forms display low affinity for acetaldehyde, the fourth is active at extremely low aldehyde concentrations (Km less than or equal to 2 microM) and allows the oxidation of the acetaldehyde formed by catalysis of alcohol dehydrogenase at pH 7.4. Different models of alcohol dehydrogenase have been examined by analysis of progress curves of ethanol oxidation obtained in the presence of low-km aldehyde dehydrogenase. According to the only acceptable model, when the acetaldehyde concentration is kept low by the action of aldehyde dehydrogenase, NADH no longer binds to alcohol dehydrogenase, but acetaldehyde still competes with ethanol for the active site of the enzyme. The seven kinetic parameters of the two enzymes (four for alcohol dehydrogenase and three for aldehyde dehydrogenase) and the equilibrium constant of the reaction catalyzed by alcohol dehydrogenase have been determined by applying a new fitting procedure here described.
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PMID:An enzymatic model for rat liver alcohol dehydrogenase in the presence of low-Km aldehyde dehydrogenase. 218 64

Asexual reproductive development can be initiated in Aspergillus nidulans in the presence of excess nutrients through artificial induction of the developmental regulatory genes brlA or abaA by fusing the genes to the promoter from the alcohol dehydrogenase I gene (alcA) and culturing cells in the presence of an inducing alcohol. Artificially induced development completely inhibits growth and represses expression of the endogenous alcA gene and the coordinately controlled aldehyde dehydrogenase gene (aldA). Repression of alcA and aldA expression probably occurs at both the transcriptional and posttranslational levels. We propose that developmental induction results in a generalized metabolic shutdown, leading to an inability of cells to acquire nutrients from the growth medium. Self-imposed nutrient limitation could reinforce the primary developmental stimulus and ensure progression through the asexual reproductive pathway.
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PMID:Developmental repression of growth and gene expression in Aspergillus. 219 67

Mice (Mus musculus) from three genetic strains with variable responses to ethanol challenge (BALB/c, C57BL/6J and 129/ReJ) were used to evaluate the effect of ethanol feeding on hepatic mRNA specific to the two primary enzymes of ethanol metabolism; alcohol dehydrogenase (ADH; E.C. 1.1.1.1) and aldehyde dehydrogenase (ALDH; E.C. 1.2.1.3). Adh-1 (ADH) and Ahd-2 (ALDH) specific mRNA were evaluated on the livers of ethanol-fed mice and from their age, sex and genotype matched controls (using an isocaloric liquid diet). C57BL/6J (alcohol resistant) mice show a significant (approx. 200%) increase in ADH-1 mRNA levels after ethanol treatment, compared to their matched controls. BALB/c (alcohol sensitive) mice have approximately a 20% increase with ethanol treatment while 129/ReJ (alcohol sensitive) mice show a slight reduction in the ADH-1 specific mRNA following ethanol feeding. A strain-specific pattern is also apparent in the AHD-2 mRNA as a result of ethanol feeding in the experimental animals. C57BL/6J mice have an increase and BALB/c mice show no apparent change in the AHD-2 mRNA. 129/ReJ mice fed an ethanol diet, on the other hand, appear to have a decrease in the level of AHD-2 hepatic mRNA as compared to their matched controls. The relative mRNA levels of the two genes correlate well with the respective enzyme activity levels, but for mice on the control diet only. Ethanol feeding, which causes an apparent reduction in hepatic ADH enzyme activity in BALB/c and 129/ReJ and an apparent increase in ALDH activity in C57BL/6J (under the experimental protocols used) also alters the mRNA levels specific to the two genes. However, changes in the mRNA levels after ethanol feeding cannot be directly related to the changes seen in enzyme activity. The observed steady state level of AHD-2 mRNA and the increase in ALDH activity after ethanol feeding, which is unique to C57BL/6J mice, is expected to offer a faster clearance (metabolism) of acetaldehyde, the toxic metabolite, and may be responsible for, or contribute to, the relative resistance of this strain to ethanol.
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PMID:Studies with cDNA probes on the in vivo effect of ethanol on expression of the genes of alcohol metabolism. 222 72

The effect of different amounts of orally ingested ethanol on plasma alcohol dehydrogenase (ADH) and erythrocyte aldehyde dehydrogenase (ALDH), as well as on the blood ethanol and acetaldehyde levels, was examined in healthy nonalcoholic subjects. The genotypes at ADH2 and ALDH2 locus were identified in enzymatically amplified blood DNA by hybridization with allele-specific oligonucleotides. While the Japanese subject was found to be genotypically heterozygous for both ADH2 and ALDH2, the Caucasian subjects were genotypically homozygous normal for these alleles. A faster ethanol elimination associated with a higher blood acetaldehyde level was observed in the Japanese subject as compared to Caucasian subjects. However, no significant change in ADH and ALDH enzyme activities was detected as the result of acute ethanol intake.
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PMID:Effect of acute ethanol drinking on alcohol metabolism in subjects with different ADH and ALDH genotypes. 222 44

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.
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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.
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PMID:Different types of formaldehyde-oxidizing dehydrogenases in Nocardia species 239: purification and characterization of an NAD-dependent aldehyde dehydrogenase. 224 Nov 49

There are at least three alcohol dehydrogenases in Aspergillus nidulans. ADHII has been observed in polyacrylamide gels stained for ADH activity but, unlike ADHI and ADHIII, no physiological function has been attributed to it. This paper describes mutations that have been isolated from strains carrying a deletion in the structural gene for ADHI (alcA) and its adjacent positively-acting regulatory gene (alcR) that restore some ability to utilise ethanol as a carbon source. The mutations map at three loci, and all show elevated levels of the ADHII staining band. An assay for ADHII has been developed. The growth on ethanol has been shown to be dependent on the previously identified aldehyde dehydrogenase (structural gene, aldA). Two of the mutations, alcD and alcE, represent newly discovered mutations affecting ethanol utilisation, while the third mutation is in amdA, a previously described trans-acting regulatory protein.
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PMID:The identification of mutations in Aspergillus nidulans that lead to increased levels of ADHII. 224 74

The effects of short-term intraperitoneal injection of diluted almond or anis oil on heart lactate dehydrogenase isoenzymes, liver alcohol dehydrogenase and subcellular aldehyde dehydrogenase were studied in the female mouse. Hepatic alcohol dehydrogenase was induced from control by administration of almond oil 3.2 g/kg/d for 7 days, or anis oil 1.6 g/kg/d for 7 days. Treatment with almond but not anis oil inhibited both cytoplasmic and mitochondrial liver aldehyde dehydrogenase. The mitochondrial isoenzyme with an apparently low Km was also inhibited by the almond oil trial. No significant changes occurred in heart lactate dehydrogenase isoenzymes by the treatments used. The enzymatic inhibition kinetics were found to be non-competitive. The apparent Km for almond-treated mouse aldehyde dehydrogenase was greater than the controls. This indicates lower substrate affinity for almond oil than for acetaldehyde. The results suggest adverse hepatic metabolic interaction between almond oil and alcohol.
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PMID:Effect of almond and anis oils on mouse liver alcohol dehydrogenase, aldehyde dehydrogenase and heart lactate dehydrogenase isoenzymes. 226 Jan 16

Protein-acetaldehyde adducts (protein-AAs) are formed in vivo during chronic alcohol ingestion. These protein-AAs reported thus far include a 37KD protein-AA in liver cytosol, cytP450IIE 1-AA in hepatic microsomes, hemoglobin-AA, and serum protein-AAs. It has been postulated that acetaldehyde or perhaps a reactive acetaldehyde radical generated by the microsomal ethanol oxidizing system (MEOS or cytP450IIE1) explains the formation of the cytP450IIE1-AA. The source of acetaldehyde responsible for the formation of the cytosolic 37KD protein-AA has not been determined. In this report, we have examined the effects of pyrazole (an ADH inhibitor) and cyanamide (an aldehyde dehydrogenase inhibitor) on the formation of the 37KD liver protein-AA in vivo and in vitro. It was found that feeding rats with an alcohol-containing liquid diet supplemented with cyanamide enhanced while a diet supplemented with pyrazole completely abolished the formation of the 37KD liver protein-AA. The liver of rats fed the pyrazole supplemented alcohol-containing diet showed significantly higher content of cytP450IIE1 than that of rats fed the diet containing alcohol alone. On the other hand, feeding the cyanamide supplemented alcohol-containing liquid diet did not further enhance the content of cytP450IIE1. Similarly, adding cyanamide to the culture medium enhanced while adding 4-methylpyrazole inhibited the production of the 37KD protein-AA by cultured hepatocytes even though the combination of alcohol and 4-methylpyrazole increased the content of cytP450IIE1 2-fold over that in control cells. These results demonstrate that the formation of the 37KD liver Protein-AA is dependent on ADH and not on MEOS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Formation of the 37KD protein-acetaldehyde adduct in liver during alcohol treatment is dependent on alcohol dehydrogenase activity. 226 8

Rates of ethanol metabolism by alcohol dehydrogenase, the microsomal ethanol oxidizing system (MEOS), and catalase were similar in liver preparations from young (4-5 months) and old (24-27 months) female Fischer 344 rats. On the other hand, rates of acetaldehyde metabolism by mitochondrial aldehyde dehydrogenase (ALDH) were 15-20% lower in livers of old rats than in those of younger ones. Results with the ALDH inhibitor cyanamide indicated that a decline in ALDH activity of this magnitude would not increase acute ethanol hepatotoxicity.
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PMID:Influence of aging on ethanol and acetaldehyde oxidation in female rat liver. 227 22


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