Genetic considerations in the effects of ethanol in mice. I. Genotype-dependent alterations in alcohol dehydrogenase activity

1985 ◽  
Vol 27 (2) ◽  
pp. 158-164 ◽  
Author(s):  
Caroline H. Wang ◽  
Shiva M. Singh
Keyword(s):  
Alcohol Dehydrogenase ◽  
Racial Differences ◽  
Alcohol Intoxication ◽  
Chronic Administration ◽  
Inbred Strains ◽  
Ethanol Exposure ◽  
Ethanol Administration ◽  
Alcohol Dehydrogenase Activity ◽  
Molecular Bases ◽  
Adh Activity

Most genetic studies on individual and racial differences in sensitivity to alcohol intoxication have concentrated on genetic variations associated with structural genes for the enzymes involved in alcohol metabolism, including alcohol dehydrogenase (ADH; E.C. 1.1.1.1). We studied the ethanol-induced regulation of ADH following chronic administration of ethanol in mice. Newly weaned males from six inbred strains (BALB/c, C3H/HeSnJ, C3H/S, C57BL/6J, S.W., and 129/ReJ) were subjected to ethanol administration. Alterations in the level of liver ADH activity, relative to matched littermate controls, were evaluated. The change in ADH activity was found to be strain (genotype) specific, which may explain the contradictory results in the literature. Strains which showed induction of ADH activity, in general, reflected a strain-specific time-dependent profile. Strains which showed repression, however, were independent in the degree of repression to the duration of ethanol exposure. Such variable, ethanol-induced regulatory responses (induction/repression) in ADH activity of different genotypes may account for individual and population variations in response to alcohol. Additional work, however, is needed to establish the molecular bases of ADH inducibility and its specific role in relative susceptibility to alcohols.Key words: alcohol dehydrogenase, mice, ethanol effects.

scholarly journals Modulation of alcohol dehydrogenase and ethanol metabolism by sex hormones in the spontaneously hypertensive rat. Effect of chronic ethanol administration

1980 ◽  
Vol 186 (2) ◽  
pp. 483-490 ◽  
Author(s):  
Gloria Rachamin ◽  
J. Alain Macdonald ◽  
Samina Wahid ◽  
Jeremy J. Clapp ◽  
Jatinder M. Khanna ◽  
...  
Keyword(s):  
Alcohol Dehydrogenase ◽  
Metabolic Rate ◽  
Dehydrogenase Activity ◽  
Chronic Administration ◽  
Ethanol Metabolism ◽  
Ethanol Administration ◽  
Male And Female ◽  
Spontaneously Hypertensive ◽  
Alcohol Dehydrogenase Activity

In young (4-week-old) male and female spontaneously hypertensive (SH) rats, ethanol metabolic rate in vivo and hepatic alcohol dehydrogenase activity in vitro are high and not different in the two sexes. In males, ethanol metabolic rate falls markedly between 4 and 10 weeks of age, which coincides with the time of development of sexual maturity in the rat. Alcohol dehydrogenase activity is also markedly diminished in the male SH rat and correlates well with the changes in ethanol metabolism. There is virtually no influence of age on ethanol metabolic rate and alcohol dehydrogenase activity in the female SH rat. Castration of male SH rats prevents the marked decrease in ethanol metabolic rate and alcohol dehydrogenase activity, whereas ovariectomy has no effect on these parameters in female SH rats. Chronic administration of testosterone to castrated male SH rats and to female SH rats decreases ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in mature males. Chronic administration of oestradiol-17β to male SH rats results in marked stimulation of ethanol metabolic rate and alcohol dehydrogenase activity to values similar to those found in female SH rats. Chronic administration of ethanol to male SH rats from 4 to 11 weeks of age prevents the marked age-dependent decreases in ethanol metabolic rate and alcohol dehydrogenase activity, but has virtually no effect in castrated rats. In the intoxicated chronically ethanol-fed male SH rats, serum testosterone concentrations are significantly depressed. In vitro, testosterone has no effect on hepatic alcohol dehydrogenase activity of young male and female SH rats. In conclusion, in the male SH rat, ethanol metabolic rate appears to be limited by alcohol dehydrogenase activity and is modulated by testosterone. Testosterone has an inhibitory effect and oestradiol has a testosterone-dependent stimulatory effect on alcohol dehydrogenase activity and ethanol metabolic rate in these animals.

scholarly journals Adaptedness of Variants at an Alcohol Dehydrogenase Locus in Bromus mollis L. (Soft Bromegrass)

1976 ◽  
Vol 29 (4) ◽  
pp. 389 ◽  
Author(s):  
ADH Brown ◽  
DR Marshall ◽  
J Munday
Keyword(s):  
Alcohol Dehydrogenase ◽  
Dehydrogenase Activity ◽  
Dry Matter ◽  
Animal Species ◽  
Natural Populations ◽  
Continuous Flooding ◽  
Naturally Occurring ◽  
Alcohol Dehydrogenase Activity ◽  
Adh Activity ◽  
Bromus Mollis

Alcohol dehydrogenase is highly polymorphic in many plant and animal species. Here we report evidence that the naturally occurring, electrophoretically detectable allozyme variants of the AdhlB locus in B. mollis can respond differentially to environmental stresses. It is argued that alcohol dehydrogenase activity is specifically involved in response to these stresses. Crude extracts of predominantly selfed seeds sampled from plants of known Adh1B genotype were assayed for their ADH activity in the forward and backward reactions. The seeds from Adh~B Adh~B plants produced extracts about 12 % less active in both directions than seeds from their Adh~BAdh~B counterparts. Such Adh~BAdh~B plants were also shown to produce about 13% more dry matter when grown under continuous flooding in the greenhouse whereas no difference between genotypes was detected in control pots. The seeds of Adh~B Adh~B plants showed an advantage over the alternative homozygotes in more rapid germination at 2�C, but no difference was found at 15�C. Thus the variants are differentially adapted, and this is likely to playa role in the maintenance of the polymorphism in natural populations.

scholarly journals Alcohol dehydrogenase activity in Drosophila melanogaster: a quantitative character

1975 ◽  
Vol 26 (1) ◽  
pp. 81-93 ◽  
Author(s):  
R. D. Ward
Keyword(s):  
Drosophila Melanogaster ◽  
Alcohol Dehydrogenase ◽  
Dehydrogenase Activity ◽  
Structural Gene ◽  
Genetic Background ◽  
Quantitative Character ◽  
Alcohol Dehydrogenase Activity ◽  
Activity Modifiers ◽  
Selection For ◽  
Adh Activity

SUMMARYAlcohol dehydrogenase activity in Drosophila melanogaster may be considered as a quantitative character, since it shows many features typically associated with such traits. Although strains with the electrophoretically fast phenotype generally have activities greater than those with the slow phenotype, presumably reflecting differences in the nucleotide sequences of the structural alleles, within each electrophoretic class there is considerable variation in activity. The expression of the structural gene, in terms of ADH activity, is to some extent regulated by its genetic background. Strains homozygous for particular structural alleles respond to divergent directional selection for ADH activity. Modifiers have been located to the X, second and third chromosomes.

scholarly journals A Cladistic Analysis of Phenotypic Associations With Haplotypes Inferred From Restriction Endonuclease Mapping. I. Basic Theory and an Analysis of Alcohol Dehydrogenase Activity in Drosophila

Genetics ◽  
1987 ◽  
Vol 117 (2) ◽  
pp. 343-351 ◽  
Author(s):  
Alan R Templeton ◽  
Eric Boerwinkle ◽  
Charles F Sing
Keyword(s):  
Linkage Disequilibrium ◽  
Alcohol Dehydrogenase ◽  
Restriction Site ◽  
Cladistic Analysis ◽  
Alcohol Dehydrogenase Activity ◽  
History Of ◽  
Endonuclease Mapping ◽  
Nested Analysis ◽  
Adh Activity ◽  
Restriction Site Polymorphisms

ABSTRACT Because some genes have been cloned that have a known biochemical or physiological function, genetic variation can be measured in a population at loci that may directly influence a phenotype of interest. With this measured genotype approach, specific alleles or haplotypes in the probed DNA region can be assigned phenotypic effects. In this paper we address several problems encountered in implementing the measured genotype approach with restriction site data. A number of analytical problems arise in part as a consequence of the linkage disequilibrium that is commonly encountered when dealing with small DNA regions: 1) different restriction site polymorphisms are not statistically independent, 2) the sites being measured are not likely to be the direct cause of the associated phenotypic effects, 3) haplotype classes may be phenotypically heterogeneous, and 4) the sites that are most strongly associated with phenotypic effects are not necessarily the most closely linked to the actual genetic cause of the effects. When recombination and gene conversion are rare, the primary cause of linkage disequilibrium is history (mutational origin, genetic drift, hitchhiking, etc.). We deal with historical association directly by producing a cladogram that partially reconstructs the evolutionary history of the present-day haplotype variability. The cladogram defines a nested analysis of variance that simultaneously detects phenotypic effects, localizes the effects within the cladogram, and identifies haplotypes that are potentially heterogeneous in their phenotypic associations. The power of this approach is illustrated by an analysis of the associations between alcohol dehydrogenase (ADH) activity and restriction site variability in a 13-kb fragment surrounding the ADH locus in Drosophila melanogaster.

scholarly journals Characterization of theEscherichia coliAntifungal Protein PPEBL21

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
V. Yadav ◽  
R. Mandhan ◽  
M. Kumar ◽  
J. Gupta ◽  
G. L. Sharma
Keyword(s):  
Alcohol Dehydrogenase ◽  
Peptide Mass Fingerprinting ◽  
Hypothetical Protein ◽  
Antifungal Protein ◽  
Biological Characterization ◽  
Activity Assay ◽  
Peptide Mass ◽  
Alcohol Dehydrogenase Activity ◽  
Adh Activity

An antifungal protein isolated fromEscherichia coliBL21 (PPEBL21) and predicted to be alcohol dehydrogenase (ADH) was subjected to biological characterization. The PPEBL21, indeed, demonstrated propionaldehyde-specific ADH activity. The Km and Vmax of PPEBL21 were found to be 644.8μM and 1.2 U/mg, respectively. In-gel activity assay also showed that PPEBL21 was a propionaldehyde-specific ADH. The pI of PPEBL21 was observed to be 7.8. PPEBL21 was found to be stable up to a temperature of40∘Cwith optimum activity at pH 7.5. The decrease in pH decreased the activity of PPEBL21. These results suggested that PPEBL21 having alcohol dehydrogenase activity and stability at significantly high temperature might be an important lead antifungal molecule. Experiments were performed to identify the possible target of PPEBL21 in the pathogenA. fumigatus. Results revealed that PPEBL21 inhibited completely the expression of a 16 kDa protein inA. fumigatus. The 16 kDa protein ofA. fumigatustargeted by PPEBL21 was identified as a hypothetical protein by peptide mass fingerprinting. It is thus hypothesized that a 16 kDa factor is essentially required byA. fumigatusfor survival and its impaired synthesis due to treatment with PPEBL21 may lead to the death of pathogen.

scholarly journals Factors that modify the metabolism of ethanol in rat liver and adaptive changes produced by its chronic administration

1970 ◽  
Vol 118 (2) ◽  
pp. 275-281 ◽  
Author(s):  
L. Videla ◽  
Y. Israel
Keyword(s):  
Alcohol Dehydrogenase ◽  
Succinate Dehydrogenase ◽  
Rat Liver ◽  
Chronic Administration ◽  
Ethanol Metabolism ◽  
Gas Mixture ◽  
Ethanol Treatment ◽  
Liver Slices ◽  
Low Concentrations ◽  
Alcohol Dehydrogenase Activity

1. 2,4-Dinitrophenol (0.1mm) increases by 100–160% the rate of ethanol metabolism by rat liver slices incubated in a medium saturated with a gas mixture containing O2+CO2+N2 (18:5:77). Similar effects are produced by relatively low concentrations of arsenate (10mm). At higher concentrations (37.5 and 50mm) arsenate inhibits the rate of ethanol metabolism. 2. When liver slices are incubated under an atmosphere containing O2+CO2 (95:5) the metabolism of ethanol increases by about 100% over that obtained with O2+CO2+N2 (18:5:77). However, under these conditions the activating effect of dinitrophenol is no longer observed. 3. Chronic administration of ethanol to rats for 3–4 weeks, in doses from 3 to 8g/kg per day, increases by 70–90% the ability of the liver to metabolize ethanol. In the liver slices of these rats, although an O2+CO2+N2 (18:5:77) mixture was used, dinitrophenol does not further increase the metabolism of ethanol. If the chronic administration of ethanol is discontinued for two weeks, the rate of ethanol metabolism is lowered to control values and the activating effect of dinitrophenol is recovered. 4. No change in alcohol dehydrogenase activity was found in the liver of the rats in which the metabolism of ethanol had been increased as a result of the chronic ethanol treatment; a 40% increase in the activity of succinate dehydrogenase was observed.

Sex differences, alcohol dehydrogenase, acetaldehyde burst, and aversion to ethanol in the rat: a systems perspective

2007 ◽  
Vol 293 (2) ◽  
pp. E531-E537 ◽  
Author(s):  
María Elena Quintanilla ◽  
Lutske Tampier ◽  
Amalia Sapag ◽  
Ziomara Gerdtzen ◽  
Yedy Israel
Keyword(s):  
Alcohol Dehydrogenase ◽  
Ethanol Intake ◽  
Ethanol Administration ◽  
Sodium Pyruvate ◽  
Systems Perspective ◽  
Rate Limiting Step ◽  
Limiting Step ◽  
Rate Limiting ◽  
Adh Activity ◽  
Active Alcohol

Individuals who carry the most active alcohol dehydrogenase (ADH) isoforms are protected against alcoholism. This work addresses the mechanism by which a high ADH activity leads to low ethanol intake in animals. Male and female ethanol drinker rats (UChB) were allowed access to 10% ethanol for 1 h. Females showed 70% higher hepatic ADH activity and displayed 60% lower voluntary ethanol intake than males. Following ethanol administration (1 g/kg ip), females generated a transient blood acetaldehyde increase (“burst”) with levels that were 2.5-fold greater than in males ( P < 0.02). Castration of males led to 1) an increased ADH activity (+50%, P < 0.001), 2) the appearance of an acetaldehyde burst (3- to 4-fold vs. sham), and 3) a reduction of voluntary ethanol intake comparable with that of naïve females. The ADH inhibitor 4-methylpyrazole blocked the appearance of arterial acetaldehyde and increased ethanol intake. Since the release of NADH from the ADH·NADH complex constitutes the rate-limiting step of ADH (but not of ALDH2) activity, endogenous NADH oxidizing substrates present at the time of ethanol intake may contribute to the acetaldehyde burst. Sodium pyruvate given at the time of ethanol administration led to an abrupt acetaldehyde burst and a greatly reduced voluntary ethanol intake. Overall, a transient surge of arterial acetaldehyde occurs upon ethanol administration due to 1) high ADH levels and 2) available metabolites that can oxidize hepatic NADH. The acetaldehyde burst is strongly associated with a marked reduction in ethanol intake.

Influence of Flooding on the Alcohol Dehydrogenase Activity of Roots of Trifolium subterraneum L.

1974 ◽  
Vol 1 (1) ◽  
pp. 9 ◽  
Author(s):  
CM Francis ◽  
AC Devitt ◽  
P Steele
Keyword(s):  
Alcohol Dehydrogenase ◽  
Anaerobic Respiration ◽  
Trifolium Subterraneum ◽  
Solution Culture ◽  
Sand Culture ◽  
Flooding Tolerance ◽  
Alcohol Dehydrogenase Activity ◽  
Adh Activity ◽  
Pot Culture ◽  
Flooding Period

Flooding the roots of T. subterraneum grown in sand culture induced large (often 30-fold) increases in alcohol dehydrogenase (ADH) activity, indicative of anaerobic respiration. In pot culture the levels of ADH activity were lower in varieties of subspecies yanninicum than in varieties of subspecies brachycalycinum and subterraneum. The varieties took 6–9 days to reach maximum ADH values, indicating a flooding period of this order is suitable in varietal testing for flooding tolerance. Lower ADH levels in subspecies yanninicum were not evident when the roots were tested after 3 days in anaerobic solution culture.

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