Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Alcohol Dehydrogenase”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1992

Polymorphism of alcohol dehydrogenase, alcohol and aldehyde dehydrogenase activities: implication in alcoholic cirrhosis in white patients. The French Group for Research on Alcohol and Liver.

Two types of factors can theoretically modulate alcohol metabolism toward increased acetaldehyde production. These factors are the following: (a) individual, genetically determined isoenzymes with distinct catalytic properties, and (b) modifications of enzyme activity induced by alcohol itself or liver damage. To investigate the respective roles of these factors in white individuals, we studied the alcohol dehydrogenase phenotype, together with liver alcohol dehydrogenase and aldehyde dehydrogenase activities, in 161 patients. Patients with alcoholic cirrhosis (n = 31) were compared with three types of controls: patients with nonalcoholic cirrhosis (n = 25) and excessive (n = 62) and moderate drinkers (n = 43) without liver disease. No association between alcohol dehydrogenase-3 phenotype and alcoholic cirrhosis was found. The prevalence of atypical alcohol dehydrogenase in the four groups was less than 1%. Patients with cirrhosis, regardless of its cause, had significantly lower alcohol dehydrogenase activity than the patients without cirrhosis (p less than 0.05 and p less than 0.01 vs. excessive and moderate drinkers, respectively). Among the noncirrhotic patients, alcohol dehydrogenase activity was significantly lower in the excessive drinkers than in the moderate drinkers (p less than 0.001). Aldehyde dehydrogenase activity was not different between cirrhosis-free excessive and moderate drinkers; in contrast, compared with these two groups, it was significantly lower in the two cirrhosis groups (p less than 0.01). These results suggest that no phenotypic pattern of alcohol dehydrogenase-3 associated with alcoholic cirrhosis in white patients exists, that liver alcohol dehydrogenase activity falls as a consequence of both alcohol abuse and cirrhosis and that liver aldehyde dehydrogenase activity is unaffected by alcohol abuse and only falls after the onset of cirrhosis.

Adult↗
PubMed1989

Isoelectric focusing studies of aldehyde dehydrogenases, alcohol dehydrogenases and oxidases from mammalian anterior eye tissues.

1. Isoelectric focusing (IEF) and zymogram methods were used to examine the tissue distribution, multiplicity and substrate specificities of alcohol dehydrogenases (ADHs), aldehyde dehydrogenases (ALDHs) and ocular oxidases (EOXs) from mammalian anterior eye tissues. 2. Baboon, cattle, pig and sheep corneal extracts exhibited high ALDH activities; the corneal ALDHs were distinct from the major liver ALDHs and distinguished by their preference for medium-chain aldehydes. 3. Baboon and pig corneal extracts also showed high ADH activities, by comparison with ovine and bovine samples. Moreover, the ADHs were distinct from the major liver isozymes in pI value and substrate specificity. 4. Mammalian lens extracts exhibited significant ALDH activity of a form corresponding to the major liver cytosolic isozyme. Minor activity of the corneal enzyme was also observed in some species. 5. Lens ADH phenotypes were species-specific, and consisted of either Class II activity (baboon and sheep), Class III ADH activity (pig), or activities of both ADH classes (cattle). 6. Lens extracts also exhibited a complex pattern of ocular oxidase (EOX) activities following IEF. 7. A role in peroxidatic aldehyde detoxification is proposed for these enzymes in anterior eye tissues.

Alcohol Oxidoreductases↗
PubMed1994

Purification of acetaldehyde dehydrogenase and alcohol dehydrogenases from Thermoanaerobacter ethanolicus 39E and characterization of the secondary-alcohol dehydrogenase (2 degrees Adh) as a bifunctional alcohol dehydrogenase--acetyl-CoA reductive thioesterase.

The purification and characterization of three enzymes involved in ethanol formation from acetyl-CoA in Thermoanaerobacter ethanolicus 39E (formerly Clostridium thermohydrosulfuricum 39E) is described. The secondary-alcohol dehydrogenase (2 degrees Adh) was determined to be a homotetramer of 40 kDa subunits (SDS/PAGE) with a molecular mass of 160 kDa. The 2 degrees Adh had a lower catalytic efficiency for the oxidation of 1 degree alcohols, including ethanol, than for the oxidation of secondary (2 degrees) alcohols or the reduction of ketones or aldehydes. This enzyme possesses a significant acetyl-CoA reductive thioesterase activity as determined by NADPH oxidation, thiol formation and ethanol production. The primary-alcohol dehydrogenase (1 degree Adh) was determined to be a homotetramer of 41.5 kDa (SDS/PAGE) subunits with a molecular mass of 170 kDa. The 1 degree Adh used both NAD(H) and NADP(H) and displayed higher catalytic efficiencies for NADP(+)-dependent ethanol oxidation and NADH-dependent acetaldehyde (identical to ethanal) reduction than for NADPH-dependent acetaldehyde reduction or NAD(+)-dependent ethanol oxidation. The NAD(H)-linked acetaldehyde dehydrogenase was a homotetramer (360 kDa) of identical subunits (100 kDa) that readily catalysed thioester cleavage and condensation. The 1 degree Adh was expressed at 5-20% of the level of the 2 degrees Adh throughout the growth cycle on glucose. The results suggest that the 2 degrees Adh primarily functions in ethanol production from acetyl-CoA and acetaldehyde, whereas the 1 degree Adh functions in ethanol consumption for nicotinamide-cofactor recycling.

Acetyl Coenzyme A↗
PubMed1994

Mammalian class IV alcohol dehydrogenase (stomach alcohol dehydrogenase): structure, origin, and correlation with enzymology.

The structure of a mammalian class IV alcohol dehydrogenase has been determined by peptide analysis of the protein isolated from rat stomach. The structure indicates that the enzyme constitutes a separate alcohol dehydrogenase class, in agreement with the distinct enzymatic properties; the class IV enzyme is somewhat closer to class I (the "classical" liver alcohol dehydrogenase; approximately 68% residue identities) than to the other classes (II, III, and V; approximately 60% residue identities), suggesting that class IV might have originated through duplication of an early vertebrate class I gene. The activity of the class IV protein toward ethanol is even higher than that of the classical liver enzyme. Both Km and kcat values are high, the latter being the highest of any class characterized so far. Structurally, these properties are correlated with replacements at the active site, affecting both substrate and coenzyme binding. In particular, Ala-294 (instead of valine) results in increased space in the middle section of the substrate cleft, Gly-47 (instead of a basic residue) results in decreased charge interactions with the coenzyme pyrophosphate, and Tyr-363 (instead of a basic residue) may also affect coenzyme binding. In combination, these exchanges are compatible with a promotion of the off dissociation and an increased turnover rate. In contrast, residues at the inner part of the substrate cleft are bulky, accounting for low activity toward secondary alcohols and cyclohexanol. Exchanges at positions 259-261 involve minor shifts in glycine residues at a reverse turn in the coenzyme-binding fold. Clearly, class IV is distinct in structure, ethanol turnover, stomach expression, and possible emergence from class I.

Alcohol Dehydrogenase↗
PubMed1982

Genetic and developmental regulation of mouse liver alcohol dehydrogenase.

Alcohol dehydrogenase (EC 1.1.1.1; alcohol:NAD+ oxidoreductase) activity varies 2-fold in liver extracts prepared from different inbred mouse strains. The strain-specific variation is not present in kidney extracts of male mice and is developmentally specific in the liver, occurring in mice 25 days of age and older. Neither electrophoretic nor heat lability properties of the enzyme from 15-day-old animals are different from the enzyme in adult mice. Analysis of genetic crosses and recombinant inbred lines confirms that a single genetic locus, designated Adh-1-t, with additive alleles has a major effect in controlling the temporal difference in enzyme activity between strains. This enzyme has been purified from mouse liver, and antibodies to the enzyme have been produced in a goat. Quantitative immunoprecipitation reveals that a given quantity of antibody immunoprecipitates equivalent protein and enzyme activity from liver extracts prepared from high and low strain mice and from 5-day-old and adult mice. Enzyme from high and low strains can be purified to the same specific activity and has indistinguishable electrophoretic and heat denaturation properties. This evidence supports the hypothesis that the high liver activity in C57BL/6 mice is due to the presence of more enzyme molecules/g of liver than is found in low activity mice. Using radiolabeling and specific immunoprecipitation of alcohol dehydrogenase, it has been established that high level mice (C57BL/6) have a 2-fold greater relative rate of synthesis of liver alcohol dehydrogenase than is found in low strain mice (C3H). Thus, the action of the Adh-1-t locus in the mouse is to control the level of alcohol dehydrogenase protein in the liver by controlling the rate of synthesis of this enzyme.

Aging↗
PubMed1987

Purification and comparative studies of alcohol dehydrogenases.

Alcohol dehydrogenases from various animal and plant sources were purified by a common procedure which employed DEAE, Sephadex-G100 and affinity chromatographies. The procedure achieves an 80-130 fold purification for animal enzymes. However, only a 5-15 fold purification for plant enzymes was attained because of the instability of these enzymes. Purified alcohol dehydrogenases from animal and plant sources differ in coenzyme and substrate specificities. The enzymes from mammalian, avian and fish livers display aldehyde oxidizing and esterolytic activities in addition to alcohol oxidizing activity. However, the enzymes from plants and yeast show only the oxidative activity toward alcohols. Chemical modifications have been performed to identify amino acid residues which are essential to the oxidative and esterolytic activities of alcohol dehydrogenases.

Alcohol Oxidoreductases↗
PubMedDate not supplied

Effect of fasting on the activity and turnover of rat liver alcohol dehydrogenase.

Alcohol dehydrogenase activity in rat liver decreased with fasting to about 60% of the fed level, but the specific activities of the enzyme purified from livers of fed and 12- or 48-hr fasted animals were similar, 3.2-3.4 U/mg protein. Therefore, the decrease in enzyme activity with fasting should have resulted from a decrease in the amount of enzyme protein. Accordingly, the turnover of alcohol dehydrogenase was examined in fed and fasted rats. The fractional rate of enzyme synthesis (ks) in fed rats was determined by radioisotopic methods to be 0.13 day-1 and it increased to 0.18 day-1 after a 12- or 48-hr fast. The absolute rate of synthesis (V) and the fractional rate of degradation (kd) were calculated from these ks values and the total enzyme content in livers from animals that were fasted for 8 to 72 hr. After 48-72 hr of fasting, V decreased 16% and kd increased about 20% with respect to the fed values. Together, these changes accounted for the lowered enzyme activity in the fasted state. The rapid decrease in enzyme activity with fasting, t1/2 congruent to 16 hr, was found to be due to a rapid increase in kd from 0.14-0.16 day-1 in fed animals to 0.61 day-1 during the first 8 hr after the initiation of fast. Thereafter, kd decreased steadily to reach 0.18 day-1 after 48-72 hr of fasting.

Alcohol Dehydrogenase↗
PubMed1993

Influence of the immunization against heterologous alcohol dehydrogenase on liver alcohol dehydrogenase isozymes and alcohol abuse of rats.

The possible biochemical and immunological mechanisms of the previously discovered phenomenon of significant and prolonged decrease of alcohol abuse of albino rats after the intravenous injection of the heterologous alcohol dehydrogenase (ADH) were studied. It was found that immunization of rats against horse liver S-ADH result in the appearance of a high titre of antibodies against rat liver ADH-3 isozyme. This isozyme is responsible for the metabolism of 90% of alcohol administrated in vivo. It is shown that immunization against horse liver S-ADH leads also to a significant (2--3-fold) lowering of the activity level of ADH-3 in rat liver. The activity level of the other rat ADH isozymes, ADH-1 and ADH-2, was not found to be changed. The intravenous injection of the specific anti-(horse liver S-ADH) serum, purified by affinity chromatography on immobilized horse liver S-ADH, resulted in a significant decrease of alcohol abuse in alcohol-dependent animals. These results allow us to assume an important role of rat liver ADH-3 in the mechanism of alcohol addiction.

Alcohol Dehydrogenase↗
PubMed2000

Duplication, dicistronic transcription, and subsequent evolution of the Alcohol dehydrogenase and Alcohol dehydrogenase-related genes in Drosophila.

It has recently been discovered that the Alcohol dehydrogenase and Alcohol dehydrogenase-related genes of Drosophila melanogaster and closely related species constitute a single transcription unit and that the Alcohol dehydrogenase-related gene is exclusively expressed from a dicistronic mRNA. Here, we show that in Drosophila lebanonensis, subgenus Scaptodrosophila, Adhr: is also transcribed as a dicistronic transcript with Adh Using degenerate primers designed on the sequence of the known Adhr proteins, we have been able to amplify and sequence a partial sequence of Adhr: in species representative of the whole subgenus Drosophila. This has allowed the study of the organization and expression of Adhr: in Drosophila buzzatii. We find that in D. buzzatii Adhr is transcribed as a monocistronic transcript. Adh and Adhr are believed to originate by duplication, and our data suggest that the cotranscription of these two genes was the primitive state, and that their independent transcription in the subgenus Drosophila is derived. We can rationalize the D. buzzatii condition as being correlated with the two genes evolving independent transcriptional control. However, why these two genes with clear divergence in the functions of their proteins should remain cotranscribed in groups as divergent as the subgenus Sophophora and the subgenus Scaptodrosophila remains a mystery.

Alcohol Dehydrogenase↗
PubMed1979

[Thermal stability of lactate dehydrogenase and alcohol dehydrogenase incorporated into highly concentrated gels].

The rate constants for inactivation of lactate dehydrogenase and alcohol dehydrogenase in solution at 65 degrees C (pH 7,5) are 0,72 and 0,013 min-1, respectively. The enzyme incorporation into acrylamide gels results in immobilized enzymes, whose residual activity is 18--25% of the original one. In 6,7% gels the rate of thermal inactivation for lactate dehydrogenase is decreased nearly 10-fold, whereas the inactivation rate for alcohol dehydrogenase is increased 4,6-fold as compared to the soluble enzymes. In 14% and 40% gels the inactivation constants for lactate dehydrogenase are 6,3.10(-3) and 5,9.10(-4) min-1, respectively. In 60% gels the thermal inactivation of lactate dehydrogenase is decelerated 3600-fold as compared to the native enzyme. The enthalpy and enthropy for the inactivation of the native enzyme are equal to 62,8 kcal/mole and 116,9 cal/(mole.grad.) for the native enzyme and those of gel-incorporated (6,7%) enzyme -- 38,7 kcal/mole and 42 cal/(mole.grad.), respectively. The thermal stability of alcohol dehydrogenase in 60% gels is increased 12-fold. To prevent gel swelling, methacrylic acid and allylamine were added to the matrix, with subsequent treatment by dicyclohexylcarbodiimide. The enzyme activity of the modified gels is 2,7--3% of that for the 6,7% gels. The stability of lactate dehydrogenase in such gels is significantly increased. A mechanism of stabilization of the subunit enzymes in highly concentrated gels is discussed.

Acrylamides↗
PubMed1987

Butanol-Ethanol Dehydrogenase and Butanol-Ethanol-Isopropanol Dehydrogenase: Different Alcohol Dehydrogenases in Two Strains of Clostridium beijerinckii (Clostridium butylicum).

Alcohol-producing strains of Clostridium beijerinckii (Clostridium butylicum) produce, besides acetone, either n-butanol and ethanol or n-butanol, ethanol, and isopropanol as their characteristic products. Alcohol dehydrogenase has been isolated from a strain (NRRL B593) of C. beijerinckii producing isopropanol and from a strain (NRRL B592) not producing isopropanol. Butanol-ethanol dehydrogenase activities were present in both strains, but isopropanol dehydrogenase activity was present only in the isopropanol-producing strain. The butanol-ethanol dehydrogenase of strain NRRL B592 had M(r) 66,000 and a K(m) of 6 muM for butyraldehyde. In contrast, the butanol-ethanol-isopropanol dehydrogenase of strain NRRL B593 had a M(r) 100,000 and K(m)s of 9.5 and 1.0 mM for butyraldehyde and acetone, respectively. In a purification by four different types of separatory methods (DEAE-cellulose, hydroxyapatite, Sephacryl S-300, and Matrex Gel Red A), butanol-ethanol-isopropanol dehydrogenase activities of strain NRRL B593 were purified up to 200-fold (10 to 30% yield), and these activities were not separated. Gel electrophoresis followed by activity stain also revealed distinct mobilities for the butanol-ethanol dehydrogenase of strain NRRL B592 and the butanol-ethanol-isopropanol dehydrogenase of strain NRRL B593. In cell extracts from both strains, a higher alcohol dehydrogenase activity was measured with NADP(H) than with NAD(H). The 150- to 200-fold-purified alcohol dehydrogenase from strain NRRL B593 did not show any NAD(H)-linked activities. The K(m) for NADPH was 31 muM (with butyraldehyde as cosubstrate) and 18 muM (with acetone as cosubstrate) for the alcohol dehydrogenase of strain NRRL B593. This study showed that the alcohol dehydrogenases from two strains of C. beijerinckii differed significantly.

Journal Article↗
PubMed1976

Identiy of brain alcohol dehydrogenase with liver alcohol dehydrogenase.

A method for obtaining electrophoretically homogeneous rat liver alcohol dehydrogenase (EC 1.1.1.1) at a specific activity of 2-2.5 mumol/min per mg of protein is presented. Anti-sera prepared against the purified enzyme inhibit alcohol dehydrogenase by up to 75% and cause precipitation of virtually all the enzyme. The antisera were shown by immunoelectrophoresis of a partially purified liver homogenate to be specifically directed against alcohol dehydrogenase and were used to demonstrate that the alcohol dehydrogenases of rat brain and liver share common antigens. The total activity of alcohol dehydrogenase in rat brain homogenates is normally quite low, with as much as 10% of the total activity attributable to the activity in the blood contained within the brain; in cases of severe liver damage (induced experimentally with carbon tetrachloride) this contribution may rise to as much as 60%.

Alcohol Oxidoreductases↗
PubMed1988

A comparative study of aldehyde dehydrogenase and alcohol dehydrogenase activities in crucian carp and three other vertebrates: apparent adaptations to ethanol production.

In the final step of the pathway producing ethanol in anoxic crucian carp (Carassius carassius L.), acetaldehyde is reduced to ethanol by alcohol dehydrogenase. The presence of aldehyde dehydrogenase in the tissues responsible for ethanol production could cause an undesired oxidation of acetaldehyde to acetate coupled with a reduction of NAD+ to NADH. Moreover, acetaldehyde could competitively inhibit the oxidation of reactive biogenic aldehydes. In the present study, the distribution of aldehyde dehydrogenase (measured with a biogenic aldehyde) and alcohol dehydrogenase (measured with acetaldehyde) were studied in organs of crucian carp, common carp (Cyprinus carpio L.), rainbow trout (Salmo gairdneri Richardson), and Norwegian rat (Rattus norvegicus Berkenhout). The results showed that alcohol dehydrogenase and aldehyde dehydrogenase activities were almost completely spatially separated in the crucian carp. These enzymes occurred together in the other three vertebrates. In the crucian carp, alcohol dehydrogenase was only found in red and white skeletal muscle, while these tissues contained exceptionally low aldehyde dehydrogenase activities. Moreover, the low aldehyde dehydrogenase activity found in crucian carp red muscle was about 1000 times less sensitive to inhibition by acetaldehyde than that found in other tissues and other species. The results are interpreted as demonstrating adaptations to avoid a depletion of ethanol production, and possibly inhibition of biogenic aldehyde metabolism.

Adaptation, Physiological↗
PubMed1998

Gastrointestinal alcohol dehydrogenase.

Alcohol dehydrogenase (ADH) consists of a family of isozymes that convert alcohols to their corresponding aldehydes using NAD+ as a cofactor. The metabolism of ethanol by gastrointestinal ADH isozymes results in the production of acetaldehyde, a highly toxic compound that binds to cellular protein and DNA if not further metabolized to acetate by acetaldehyde dehydrogenase isozymes. Acetaldehyde seems to be involved in ethanol-associated cocarcinogenesis. The metabolism of retinol and the generation of retinoic acid is a function of class I and class IV ADH, and its inhibition by alcohol may lead to an alteration of epithelial cell differentiation and cell growth and may also be involved in ethanol-associated gastrointestinal cocarcinogenesis.

Acetaldehyde↗
PubMed1994

Purification and characterization of Helicobacter pylori alcohol dehydrogenase.

Alcohol dehydrogenase of Helicobacter pylori (HPADH) was purified from the soluble fraction of cultured bacteria (strain NCTC 11637) by anion exchange and affinity chromatography. On sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the 160-fold purified enzyme displayed one protein band with a mobility that corresponded to an M(r) of 38,000. Although HPADH was capable of utilizing both NADP and NAD as cofactors in alcohol oxidation, it showed a strong preference for NADP over NAD. Kinetic studies revealed a Km value of 26 mM and a kcat value of 530 min-1 for ethanol/active site at 37 degrees C in 0.1 M potassium phosphate buffer (pH 7.4). The enzyme was considerably more active toward primary aliphatic alcohols than secondary alcohols. The Km and kcat values decreased as the chain length of the alcohol increased. Benzyl alcohol was a 100 times better substrate than ethanol in terms of kcat/Km values. At neutral pH, HPADH was more effective in aldehyde reduction than in alcohol oxidation. Because of its high specific activity for ethanol (14 units mg-1) under physiological conditions, HPADH can also effectively produce acetaldehyde at higher ethanol levels. This reversed function of HPADH and the production of toxic and reactive acetaldehyde could account for at least some of the gastrointestinal morbidity associated with H. pylori infection.

Acetaldehyde↗