Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1332347 (ADH)
 2,230 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo effect of amantadine, chlorpromazine and reserpine on testicular aldehyde dehydrogenase (T-ALDH) was studied as a function of mouse strain. The effect of Leu-enkephalin and tetrahydropapaverine on rodent T-ALDH was also studied in vivo. The in vitro effect of chlorpromazine, papaverine and scopolamine on rodent subcellular T-ALDH and testicular alcohol dehydrogenase (T-ADH) were evaluated. A strain-linked difference in endogenous T-ALDH among the three mouse strains studied was determined. Individual injection of chlorpromazine or reserpine inhibited only albino ICR T-ALDH which was alleviated by pretreatment with amantadine and, thereby, suggesting antagonism between amantadine and these agents. The Leu-enkephalin administration induced T-ALDH from saline control. Tetrahydropapaverine did not influence the enzymes studied in vivo compared to an insignificant in vitro induction of T-ADH by the O-methylated analogue papaverine. Chlorpromazine noncompetitively inhibited T-ADH in vitro. The results indicate the modulation of the enzymes studied, which are involved in both detoxification of ethanol and biogenic amine-derived aldehyde intermediates, by agents affecting the endocrine system. This suggests the potential of these testicular enzymes in the evaluation of alcohol- and drug-induced endocrine adverse reactions.
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PMID:Gonadal alcohol and aldehyde dehydrogenase: in vivo and in vitro effects of psychoactive and endocrine agents. 231 66

The effect of cholinergics and an anticholinergic agent on hepatic ethanol metabolizing enzymes was studied. Short-term administration of the cholinomimetic arecoline or the anticholinergic scopolamine induced rat liver mitochondrial aldehyde dehydrogenase (L-ALDH) isoenzyme with the apparent high and low Km, respectively. In addition, scopolamine inhibited cytoplasmic L-ALDH. This suggests differential sensitivity of the L-ALDH isoenzymes to these agents. Scopolamine and the cholinomimetic pilocarpine enhanced rat and mouse liver alcohol dehydrogenase (L-ADH) in vitro, respectively. This indicates species-dependent effect of these agents on L-ADH. The results suggest interaction of the cholinergic system with ethanol metabolizing enzymes which may contribute to the peripheral action of alcohol.
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PMID:Cholinergic, anticholinergic agents and ethanol interaction. 232 54

Both aldehyde dehydrogenase (ALDH, EC 1.2.1.3) and the aldehyde dehydrogenase activity of alcohol dehydrogenase (ADH, EC 1.1.1.1) were found to coexist in Drosophila melanogaster larvae. The enzymes, however, showed different inhibition patterns with respect to pyrazole, cyanamide and disulphiram. ALDH-1 and ALDH-2 isoenzymes were detected in larvae by electrophoretic methods. Nonetheless, in tracer studies in vivo, more than 75% of the acetaldehyde converted to acetate by the ADH ethanol-degrading pathway appeared to be also catalysed by the ADH enzyme. The larval fat body probably was the major site of this pathway.
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PMID:The metabolism of ethanol-derived acetaldehyde by alcohol dehydrogenase (EC 1.1.1.1) and aldehyde dehydrogenase (EC 1.2.1.3) in Drosophila melanogaster larvae. 249 14

A much higher incidence of alcohol flushing among Orientals in comparison to Caucasians, i.e., greater than 50% vs 5%-10%, has been attributed to racial differences in alcohol-metabolizing enzymes. A large majority of Orientals are "atypical" in alcohol dehydrogenase-2 locus (ADH2), and their livers exhibit significantly higher ADH activity than the livers of most Caucasians. Approximately 50% of Orientals lack the mitochondrial aldehyde dehydrogenase (ALDH2) activity, and elimination of acetaldehyde might be disturbed. We determined by means of hybridization of genomic DNA samples with allele specific oligonucleotide probes, genotypes of the ADH2 and ALDH2 loci in Japanese alcohol flushers and nonflushers. We found that all individuals with homozygous atypical ALDH2(2)/ALDH2(2) and most of those with heterozygous atypical ALDH1(2)/ALDH2(2) were alcohol flushers, while all subjects with homozygous usual ALDH1(2)/ALDH1(2) were nonflushers. Frequency of the atypical ADH2(2) was found to be higher in alcohol flushers than in nonflushers, but the statistical significance was not established in the sample size examined.
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PMID:Genotype of alcohol dehydrogenase and aldehyde dehydrogenase loci in Japanese alcohol flushers and nonflushers. 271 75

White rats were divided into water-preferring (WP) and ethanol-preferring (EP) groups, on the basis of their preferable drink: either water or 15% solution of ethanol. Each of these groups was then subdivided into groups which were given to drink for 1 year 15% solution of ethanol (ethanol-treated) or water (controls). Alcohol dehydrogenase/aldehyde dehydrogenase activity ratios (ADH/AlDH) in livers of WP controls were considerably higher than those in EP controls. The difference in ADH/AlDH has somewhat decreased after ethanol treatment. However, this ratio remained the highest in the WP alcohol-treated group. The signs of proteinic and lipid dystrophy of the liver in alcohol-treated WP rats were expressed much more clearly than in all other groups. It is concluded that in the liver of animals with a high ADH/AlDH ratio there are favourable conditions for accumulation of a toxic hepatocyte-damaging acetaldehyde.
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PMID:[The harmful action of ethanol on the liver: the role of alcohol dehydrogenase and aldehyde dehydrogenase]. 277 67

The activities of aldehyde dehydrogenase (ALDH; EC 1.2.1.3) and alcohol dehydrogenase (ADH; EC 1.1.1.1) were measured in term placentas of 13 alcoholic women and 16 matched controls. With acetaldehyde 8 mmol/l as substrate, the ALDH activity was 29.1 +/- 12.2 and 34.4 +/- 15.3 mU/g of wet weight (mean +/- SD; p greater than 0.4) for alcoholics and controls, respectively. With 50 mumol of acetaldehyde, ALDH activity was undetectable in both groups. No ADH activity could be detected in the placentas. The weights of placentas and newborns were significantly lower in the alcoholic group (placentas: 526 +/- 116 vs. 653 +/- 77 g, p less than 0.005; newborns 2,878 +/- 417 vs. 3,595 +/- 346 g, p less than 0.001). The results suggest that in chronic alcohol abuse, the placenta plays a negligible role in the metabolism of ethanol and acetaldehyde.
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PMID:Placental alcohol metabolism in chronic alcohol abuse. 279 89

The alcR positive control gene is necessary for the expression of both alcA (coding for alcohol dehydrogenase ADH I), and aldA (coding for aldehyde dehydrogenase, AldDH) in Aspergillus nidulans. Using a cloned alcR probe and Northern blots analysis we show that: (1) alcR itself is inducible; (2) alcR inducibility depends on the expression of the alcR gene itself; and (3) alcR is subject to carbon catabolite repression and its expression is controlled by the negatively acting creA wide specificity gene. The repression of alcR is sufficient to explain the carbon catabolite repression of ADH I and AldDH.
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PMID:Regulation of alcR, the positive regulatory gene of the ethanol utilization regulon of Aspergillus nidulans. 283 22

1. Liver biopsies were performed in healthy control subjects and in subjects with alcoholic and non-alcoholic liver disease in order to examine alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase [ALDH; aldehyde dehydrogenase (NAD+); EC 1.2.1.3] activities. Erythrocyte ALDH and ethanol metabolism were also investigated in the same subjects. 2. Fifteen per cent of the subjects studied (seven of 48 subjects tested) presented atypical ADH activity, characterized by elevated activity at pH 7.4 or 8.8 compared with that found in subjects with the usual ADH form. However, the ethanol elimination curves obtained in two subjects with atypical ADH were indistinguishable from the kinetics of the group with normal ADH. Subjects displaying atypical ADH activity showed normal liver and erythrocyte ALDH activities. 3. Considering only the subjects with the normal ADH form, hepatic ADH activity was unaltered in subjects with non-alcoholic liver disease (chronic hepatitis or cirrhosis) and in those with alcoholic steatosis. Subjects with alcoholic hepatitis or alcoholic cirrhosis showed a lower ADH activity compared with the healthy control group. 4. In spite of the changes detected in subjects with alcoholic liver disease, curves of blood ethanol concentration after oral administration of 0.4 g of ethanol/kg were indistinguishable between the alcoholic hepatitis group and the control group. 5. Hepatic ALDH activity, assayed at 300 mumol/l acetaldehyde, was found to be diminished in all liver pathologies investigated, regardless of their aetiology. Nevertheless, erythrocyte ALDH activity was not modified in subjects with non-alcoholic or alcoholic liver disease. As a result of these findings, no relationship was found between hepatic and erythrocyte ALDH.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of liver disorders on ethanol elimination and alcohol and aldehyde dehydrogenase activities in liver and erythrocytes. 292 May 34

The distribution of genetic variants (or gene markers) for alcohol dehydrogenase, aldehyde dehydrogenase, aldehyde oxidase, and aldehyde reductase isozymes has been examined among 12 inbred strains of mice. Electrophoretic variants are described for the major liver and stomach alcohol dehydrogenase isozymes (ADH-A2 and C2); liver, kidney, and stomach aldehyde dehydrogenase isozymes (AHD-1; AHD-2; AHD-4); a liver-specific aldehyde reductase (AHR-A2); and a liver aldehyde oxidase isozyme (AOX-2). Genetically determined activity variants were observed for a testis-specific aldehyde dehydrogenase (AHD-6); liver and kidney aldehyde reductase isozymes (AHR-3 and AHR-4); and the major liver AOX isozyme (AOX-1). These variants may serve as useful gene markers in alcohol research involving animal model studies with inbred strains in mice.
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PMID:Genetic variants of enzymes of alcohol and aldehyde metabolism. 293 67

Differences in the pharmacokinetics of alcohol absorption and elimination are, in part, genetically determined. There are polymorphic variants of the two main enzymes responsible for ethanol oxidation in liver, alcohol dehydrogenase and aldehyde dehydrogenase. The frequency of occurrence of these variants, which have been shown to display strikingly different catalytic properties, differs among different racial populations. Since the activity of alcohol dehydrogenase in liver is a rate-limiting factor for ethanol metabolism in experimental animals, it is likely that the type and content of the polymorphic isoenzyme subunit encoded at ADH2, beta-subunit, and at ADH3, the gamma-subunit, are contributing factors to the genetic variability in ethanol elimination rate. The recent development of methods for genotyping individuals at these loci using white cell DNA will allow us to test this hypothesis as well as any relationship between ADH genotype and the susceptibility to alcoholism or alcohol-related pathology. A polymorphic variant of human liver mitochondrial aldehyde dehydrogenase, ADLH2, which has little or no acetaldehyde oxidizing activity has been identified. Individuals with the deficient ALDH2 phenotype do not have altered ethanol elimination rates but they do exhibit high blood acetaldehyde levels and dysphoric symptoms such as facial flushing, nausea and tachycardia, after drinking alcohol. Because acetaldehyde is so reactive, it binds to free amino groups of proteins including a 37 kilodalton hepatic protein-acetaldehyde adduct and may elicit an antibody response. We would predict that individuals who have low ALDH2 activity because of liver disease or because they have the inactive ALDH2 variant isoenzyme might form more protein-acetaldehyde adducts and elicit a greater immune response. These adducts may represent good biological markers of alcohol abuse and may also play a role in liver injury due to chronic alcohol consumption.
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PMID:Genetic polymorphism of enzymes of alcohol metabolism and susceptibility to alcoholic liver disease. 306 25


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