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)

Genetic polymorphisms of two major alcohol-metabolizing enzymes-i.e., one of the class I alcohol dehydrogenase isozymes (ADH2) and the mitochondrial aldehyde dehydrogenase (ALDH2)-exist in Japanese and other Orientals but not in Caucasians. Liver ADH activity of about 90% of Orientals is much higher than that of most Caucasians, while approximately 50% of Orientals lack the ALDH2 activity. The genetic differences have been implicated in the high incidence of alcohol sensitivity observed in Orientals. We determined, by means of hybridization of genomic DNA samples with allele-specific synthetic oligonucleotide probes, genotypes of the ADH2 and the ALDH2 loci of Japanese with alcoholic liver diseases and of control subjects. No significant difference between the patient and control groups was found in the ADH2 genotypes. A remarkable genetic difference between the two groups was found in the ALDH2 locus. The frequency of the typical (Caucasian-type) ALDH1(2) gene was found to be .65 and that of the atypical (Oriental type) ALDH2(2) gene was .35 in the controls, while these were .93 and .07, respectively, in the patients. Thus, most (20 of 23) of the Japanese patients were homozygous Caucasian type ALDH1(2)/ALDH1(2), only three were heterozygous ALDH1(2)/ALDH2(2), and none of the patients were homozygous Oriental type ALDH2(2)/ALDH2(2). The results indicate that Japanese with the atypical ALDH2(2) allele are at a much lower risk in developing the alcoholic liver diseases than are those with homozygous, usual (Caucasian-type) ALDH1(2)/ALDH1(2), presumably owing to their sensitivity to alcohol intoxication.
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PMID:Genotypes of alcohol-metabolizing enzymes in Japanese with alcohol liver diseases: a strong association of the usual Caucasian-type aldehyde dehydrogenase gene (ALDH1(2)) with the disease. 318 38

The effect of pretreatment with amantadine (AMN) on chlorpromazine (CPZ) and reserpine (RES)-produced behavioral depression was studied in the male mouse. The effect of this treatment on hepatic alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenase (L-ALDH), which catalyze the metabolism of biogenic amine aldehydes, was also investigated. Administration of AMN, 100 mg/kg, initially decreased spontaneous locomotor activity from saline control. Pretreatment with identical dose of AMN 15 min before small dose of CPZ or RES, 0.2 mg/kg, further suppressed motility compared to animals receiving the individual AMN, CPZ or RES treatment. Using a second dose regimen of these compounds, given 5 hr post the initial injection, altered L-ALDH as a function of its subcellular localization. This was demonstrated by AMN-produced induction of mitochondrial, but not cytoplasmic L-ALDH. Likewise, a moderate but not statistically significant increase in endogenous mitochondrial L-ALDH was determined subsequent to the CPZ treatment. Treatment with AMN prior to CPZ reduced the enhancement of L-ALDH to control levels. The RES dose used was devoid of action on remainder of hepatic enzymes measured. The results indicate that AMN possesses central depressant property which was potentiated by CPZ and RES. The enzymatic data suggest antagonism between AMN and CPZ on induction of mitochondrial L-ALDH.
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PMID:Effect of amantadine on chlorpromazine and reserpine-induced behavioral depression in the mouse. 322 46

The effect of acute treatment of two major Tourette's drugs, haloperidol and pimozide given 60 mg/kg, IP over 48 hr, on hepatic alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenase was studied in the female mouse. The effect of these drugs on heart cytoplasmic lactate dehydrogenase (H-LDH) isoenzyme LDH1 (M) and LDH2 (H) was also measured. Both haloperidol and pimozide significantly inhibited cytoplasmic L-ADH and L-ALDH from controls. Conversely, the haloperidol treatment was associated with induction of both H-LDH isoenzymes studied. Injection of pimozide, 25 mg/kg, IP, to rats with preference to ethanol drinking, caused aversion to voluntary intake of 5% ethanol consumption. This suggests that pimozide produced inhibition of L-ADH in another species and thereby causing aversion to ethanol drinking or may be related to dopaminergic antagonist property. This inhibition of these drugs on the oxidative and reductive pathways of biogenic amine aldehydes may be implicated in and/or associated with the underlying mechanism(s) of action.
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PMID:Tourette's medications: effect on minor oxidative and reductive pathways of biogenic amines. 322 45

Mice (Mus musculus) from four genetic strains (BALB/c, C57BL/6J, 129/ReJ, and SW) and their F1 hybrids (SWxBALB/c, C57BL/6JxBALB/c, and C57BL/6Jx129/ReJ) were used to evaluate the effect of ethanol on the activity of the two primary enzymes, alcohol dehydrogenase (ADH; E.C.1.1.1.1) and aldehyde dehydrogenase (ALDH; E.C. 1.2.1.3), of alcohol metabolism. Three week-old male mice (12-16 g) were placed on liquid diet (5% ethanol) while a weight-matched littermate control was fed isocaloric maltose-dextrin in place of ethanol. Animals were sacrificed after 3 weeks and the liver and stomach were excised for biochemical analysis. Although the ethanol feeding did not influence the stomach ADH and ALDH activity levels, these enzymes in the liver were affected. The liver ADH activity was depressed to varying degrees in all mouse genotypes studied. Also, the ethanol feeding altered the liver-ALDH activity, which was highly variable and genotype specific. The mice of C57BL/6J and F1 C57BL/6JxBALB/c, both relatively resistant genotypes, exhibited significant increase in liver ALDH-(cytosolic and whole liver homogenate) activity. The response in the other genotypes were not significantly different from their matched controls. The relative resistance of the C57BL/6J strain may be associated with the increase in liver ALDH activity which is expected to facilitate the elimination of acetaldehyde, the toxic metabolite. The results from the selected F1 crosses indicate a multigene system regulating the inducibility of the liver ALDH. The relative sensitivity of different genotypes may be attributed to inducibility components regulating the liver enzyme activity, particularly liver ALDH following challenges with ethanol. These observations may offer a new approach in explaining extensive variability in response to alcohols in most populations.
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PMID:Genetically determined response of hepatic aldehyde dehydrogenase activity to ethanol exposures may be associated with alcohol sensitivity in mouse genotypes. 327 58

Electrophoretic and activity variation of the stomach and ocular isozyme of aldehyde dehydrogenase (designated AHD-4) was observed between C57BL/6J and SWR/J inbred strains of mice. The phenotypes were inherited in a normal mendelian fashion, with two alleles at a single locus (Ahd-4) showing codominant expression. The alleles assorted independently of those at Adh-3 [encoding the stomach and ocular isozyme of alcohol dehydrogenase (ADH-C2)] on chromosome 3. Three chromosome 11 markers, hemoglobin alpha-chain (Hba), trembler (Tr), and rex (Re), were used in backcross analyses which established that Ahd-4 is closely linked to trembler. The distribution patterns for stomach and ocular AHD-4 phenotypes were examined among SWXL recombinant inbred mice, and those for stomach and ocular ADH-C2 among BXD recombinant inbred strains. The data provided evidence for the genetic identity of stomach and ocular ADH-C2 and of stomach and ocular AHD-4.
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PMID:Genetics of ocular NAD+-dependent alcohol dehydrogenase and aldehyde dehydrogenase in the mouse: evidence for genetic identity with stomach isozymes and localization of Ahd-4 on chromosome 11 near trembler. 340 74

Activity variants of the stomach and ocular isozyme of aldehyde dehydrogenase (AHD-4) were observed among inbred strains of mice. The phenotypes were inherited in a normal mendelian fashion, with two alleles showing codominant expression at a single locus (Ahd-4). Linkage data indicated that Ahd-4 is localized on chromosome 11 near Hba (alpha hemoglobin locus), and segregated independently of Adh-3, encoding the stomach and ocular isozyme of alcohol dehydrogenase (ADH-C2).
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PMID:Genetics of stomach and ocular alcohol dehydrogenase and aldehyde dehydrogenase in the mouse. 342 79

The activities of human lens aldehyde dehydrogenase, glyceraldehyde-3-P dehydrogenase, polyol dehydrogenase, triosephosphate isomerase and glutathione reductase were measured prior to and following their exposure to oxidation. Active oxygen species were generated by the reaction of either methylene blue or riboflavin with light over a 60 minute time interval. It was found that oxidants generated by both photosensitizers rapidly diminish the activities of glutathione reductase and glyceraldehyde-3-P dehydrogenase but do not alter the activity of triosephosphate isomerase. After an initial time delay, PD activity likewise was abolished and 50% ADH activity remained at the end of the reaction sequence. All enzyme activities affected declined at a faster rate in the presence of methylene blue than riboflavin, and methylene blue itself served as an enzyme inhibitor to the catalytic function of glutathione reductase and glyceraldehyde-3-P dehydrogenase. These findings suggest that singlet oxygen formation not only alters the properties of the crystallin components of the human lens but also damages several of their enzyme associated counterparts.
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PMID:Oxidative damage to human lens enzymes. 356 48

The effects of taurine, its initial precursor L-cysteine, and the major metabolite taurocholic acid on two ethanol-mediated responses in rodents were studied. Administration of a single dose of taurocholic acid reduced voluntary intake of a 5% ethanol solution by the rat. In the mouse, taurine had no effect on alcohol drinking or on the central depressant action of ethanol, as measured by the duration of ET-produced loss of the righting reflex. Likewise, taurocholic acid and L-cysteine did not significantly influence the duration of ethanol-narcosis time from control mice. Also studied were the effects of acute and short-term (7 or 10 days) administration of these compounds on hepatic ethanol and acetaldehyde metabolizing enzymes. Short-term administration of an equimolar concentration of taurine enhanced endogenous NADP-linked rat liver aldehyde dehydrogenase (L-ALDH) as contrasted with inhibition of the same enzyme by L-cysteine. Short-term (7 days) treatment with L-cysteine induced rat liver NAD-linked ALDH, but acute (single dose) treatment did not. Taurocholic acid short-term administration caused an induction and an inhibition of endogenous mouse liver alcohol dehydrogenase (L-ADH) and L-ALDH, respectively. The results suggest that taurine does not directly interact with ethanol. However, its major metabolite, taurocholic acid, may cause rapid metabolic conversion of ethanol to acetaldehyde by induction of L-ADH, which is then slowly metabolized due to a concomitant inhibition of L-ALDH. This may cause a build-up of acetaldehyde and thereby produce adverse reactions similar to those resulting from the combination of disulfiram and ethanol.
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PMID:Differential response of NADP-linked hepatic aldehyde dehydrogenase toward taurine: implication for behavioural effects of ethanol. 362 78

The effect of short-term intake of LiCl in drinking water on mouse liver alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenase (L-ALDH) was studied in the albino and in the C57BL mouse strain. The Li-treatment induced initially mitochondrial L-ALDH which was followed by L-ADH in the albino mouse. This was not apparent in the C57 mouse strain. There was an induction of hepatic L-ADH and L-ALDH in the C57BL mouse subsequent to short-term administration of chlorpromazine (CPZ). Coadministration of LiCl with CPZ resulted in moderate enhancement of enzymatic activity per mg wet liver tissue from corresponding controls. Chlorpromazine inhibited rat liver and testicular ADH when tested in vitro. Both cytoplasmic and mitochondrial ALDH were not altered by CPZ in vitro. The results suggest that alcohol consumption during treatment with both drugs studied could evoke metabolic adverse reactions which appear to be both species and strain dependent.
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PMID:Effect of separate and combined treatment with chlorpromazine and lithium on mouse liver alcohol and aldehyde dehydrogenase. 609 69

In vivo and in vitro studies have been presented to suggest an interrelationship between drugs used in the management of, or known for their induction of extrapyramidal disorder and certain dehydrogenase enzymes involved in this metabolic pathway of the biogenic amines. This relationship is discussed to advance a tentative hypothesis explaining a possible underlying mechanism and to provide an explanation for the implication of alcohol consumption in worsening of extrapyramidal symptoms during certain pharmacotherapy. The major neutral metabolites of the biogenic amines acted as substrate to or induced rat liver alcohol dehydrogenase (L-ADH) and drugs used in the management of tardive dyskinesia similarly induced L-ADH. This induction of L-ADH could enhance the metabolic biotransformation of the neutral metabolites of the monoamines. Conversely, drugs known to evoke extrapyramidal dyskinesias inhibited rat liver aldehyde dehydrogenase (L-ALDH). This inhibition of ALDH may give rise to toxic condensation products between biogenic amine aldehydes and their precursors which may be implicated in certain dyskinesias. It is proposed that one of the mechanisms underlying the biogenic amine involvement in the pathogenesis of certain extrapyramidal diseases may include a critical balance between their reductive and oxidative routes of metabolism.
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PMID:Extrapyramidal disorders: a possible underlying mechanism. 613 36


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