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)

Behavioral, biochemical and histological techniques were used to evaluate the possible interaction between a lithium salt and ethanol. Injection of a single dosage of ethanol into mice pretreated with LiCl for 14 days enhanced spontaneous locomotor activity for the initial 60 min of testing compared to respective control. Drinking of 0.4% of LiCl solution for 25 consecutive days induced hepatic alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenase (L-ALDH). The LiCl treatment increased Vmax of both enzymes in the same order and magnitude. The apparent Km of L-ADH was increased by LiCl while that of L-ALDH remained unchanged from respective controls. Organ histopathology indicates decreased germinal activity of the mouse spleen by the LiCl treatment. A mild chronic perivascular inflammation and slight hypercellularity of the myocardium was also noted in the heart of LiCl-treated mice.
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PMID:Behavioral, metabolic and histological aspects of lithium and ethanol interaction. 631 9

The in vitro effect of propranolol, a beta-receptor blocking agent, on specific activity of hepatic alcohol dehydrogenase (L-ADH) and aldehyde dehydrogenase (L-ALDH) was studied in the male and in the female rat. The presence of propranolol, in the dose range of 3 x 10(-4) M to 10(-3) M concentration in the reaction mixture noncompetitively inhibited female but not male L-ADH. Conversely, significant enhancement of mitochondrial but not cytoplasmic L-ALDH occurred in the presence of propranolol, between 10(-3) M and 10(-5) M concentration, in both sexes. The alteration of hepatic ethanol and acetaldehyde metabolizing enzymes by propranolol suggest both gender difference and possible contraindication of use of this drug in alcoholic patients.
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PMID:Gender and propranolol-ethanol interaction. 634 30

The in vivo and in vitro effect of chlorpromazine (CPZ) on female mouse liver alcohol dehydrogenase (L-ADH) and mitochondrial aldehyde dehydrogenase (L-ALDH) was studied as a function of illumination conditions. Chlorpromazine was injected once daily in a gradual dose build-up from 5 to 30 mg/kg, i.p., over 21 consecutive days. This resulted in a noncompetitive inhibition of endogenous L-ALDH of mice housed under UV light exposure but not those maintained under standard laboratory fluorescent lighting and receiving identical CPZ treatment. No changes occurred in L-ADH in vivo but a noncompetitive inhibition of mouse L-ADH was determined in the presence of 50 muMol of CPZ in vitro. The results are discussed in reference to possible toxic mechanism underlying CPZ and ethanol interaction.
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PMID:Modification of mouse liver alcohol and aldehyde-dehydrogenase by chlorpromazine. 635 84

Electrophoretic and activity variants for the C2 isozyme of alcohol dehydrogenase (ADH-C2), the mitochondrial isozyme of aldehyde dehydrogenase (AHD-A2) and aldehyde oxidase isozymes (AOX-1; AOX-2) in inbred strains of Mus musculus were used to map the genes encoding these enzymes on the mouse genome. Adh-3 (encoding ADH-C2) was localized on chromosome 3 and was closely linked to a cis-acting regulator locus (Adh-3-t), which determined ADH-C2 activity in male reproductive tissues. Ahd-1 (encoding AHD-A2) was found on chromosome 4 near Gpd-1 (encoding the liver isozyme of glucose-6-phosphate dehydrogenase), whereas the aldehyde oxidase loci (Aox-1, Aox-2) were closely linked on chromosomes 1 near Id-1 (encoding isocitrate dehydrogenase).
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PMID:Genetic regulation of alcohol dehydrogenase, aldehyde dehydrogenase and aldehyde oxidase isozymes in the mouse. 699 77

It has previously been reported that isolated rat hepatocytes rapidly and completely metabolize high concentrations of 4-hydroxy-2,3-(E)-nonenal (4-HNE). However, until this report, the degree to which oxidative-reductive and nonoxidative metabolic pathways function in the depletion of 4-HNE by isolated rat hepatocytes has been speculative. The objective of the present study was to quantitate the extent to which cellular aldehyde dehydrogenases (ALDH; EC 1.2.1.3.), alcohol dehydrogenase (ADH; EC 1.1.1.1.), and glutathione S-transferases (GST; EC 2.5.1.18) function simultaneously during hepatocellular metabolism of 4-HNE. Hepatocytes were incubated with varying concentrations of 4-HNE (50, 100, 250 microM) and reversed-phase HPLC was used to quantitate 4-HNE and the oxidative and reductive metabolites, 4-hydroxy-2-nonenoic acid and 1,4-dihydroxy-2-nonene, respectively. Conjugative metabolism of 4-HNE was determined from the depletion of cellular reduced glutathione (GSH) and concomitant formation of a GSH-4-HNE adduct detected as 2,4-dinitrofluorobenzene derivatives measured by reversed-phase HPLC. Hepatocellular elimination of 4-HNE was estimated at rates of 1.666, 0.902, and 0.219 nmol min-1 10(6) hepatocytes-1 for 50, 100, and 250 microM aldehyde, respectively. At aldehyde concentrations of 50, 100, and 250 microM the maximal concentrations of oxidative (acid) metabolites formed were 5.9, 12.7, and 28.9 nmoles 10(6) hepatocytes-1, whereas the concentrations of the reductive (diol) metabolite were 0.4, 12.6, and 42.3 nmoles 10(6) hepatocytes-1, respectively. The presence of 4-methylpyrazole or cyanamide abolished formation of the reductive metabolite 1,4-dihydroxy-2-nonene or the oxidative metabolite 4-hydroxy-2-nonenoic acid in hepatocyte suspensions. At all 4-HNE concentrations evaluated, hepatocellular glutathione was not completely depleted by the aldehyde and the depletion of cellular reduced GSH corresponded to the production of the GSH-4-HNE conjugate. Metabolism by the alcohol/aldehyde dehydrogenase pathways accounted for approximately 10% of the 4-HNE elimination, while bioconversion by GST represent 50-60% of the total 4-HNE removal by hepatocytes. The enzymatic pathways responsible for the remaining 40% of 4-HNE metabolism remain to be identified. Taken together these results describe the quantitative and dynamic importance of oxidative, reductive, and nonoxidative routes in the metabolism and detoxification of 4-HNE.
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PMID:The hepatocellular metabolism of 4-hydroxynonenal by alcohol dehydrogenase, aldehyde dehydrogenase, and glutathione S-transferase. 784 Jun 16

An extract of Radix Puerariae (RP), an herb long used in traditional Chinese medicine for alcohol addiction and intoxication, was shown to suppress the free-choice ethanol intake of ethanol-preferring Syrian golden hamsters. Two isoflavones, diadzein (4',7-dihydroxyisoflavone) and daidzin (7-glucoside of daidzein), isolated from the extract were shown to account for this effect. Daidzin administered intraperitoneally at 150 mg/kg/day suppressed free-choice ethanol intake by > or = 50%. Such effect has been confirmed in a total of 79 consecutive hamsters studied over a period of more than a year. Daidzein was less potent and a higher dose (230 mg/kg/day) was required to produce similar effect. RP-, daidzin-, and daidzein-treated hamsters appeared to remain healthy and exhibited no significant change in body weight and water or food intake. In vitro, daidzin and daidzein inhibited human mitochondrial aldehyde dehydrogenase (ALDH-2) and gamma gamma-alcohol dehydrogenase (gamma gamma-ADH), respectively. However, at doses that suppressed ethanol intake, daidzin and daidzein had no effect on overall acetaldehyde and ethanol metabolism in hamsters. These findings clearly distinguish the action(s) of daidzin and daidzein from those of the classic, broad acting inhibitors of ALDH (e.g. disulfiram) and class I ADH isozymes (e.g. 4-methylpyrazole), and identify them as a new class of compounds that offer promise as safe and effective therapeutic agents for alcohol abuse.
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PMID:Therapeutic lessons from traditional Oriental medicine to contemporary Occidental pharmacology. 803 68

The relative contribution of the aldehyde dehydrogenase (EC 1.2.1.3, ALDH) and glutathione (GSH) conjugate system to the degradation of (E)-4-hydroxy-2-nonenal (4HN), a toxic breakdown product arising from lipid peroxidation, was investigated in rat liver. Significant increases in the contents of 4HN and hexanal (HA) and a decrease of ALDH but not alcohol dehydrogenase (EC 1.1.1.2, ADH) activity were recognized in rat liver following administration of carbon tetrachloride (3 ml/kg, p.o.). Hepatic ALDH activity was correlated with HA production (r = -0.82, P < 0.01) but not with 4HN. When lipid peroxidation was induced by t-butyl hydroperoxide, the ratio of HA to 4HN production in the liver of rats pretreated with the ALDH inhibitor, cyanamide (100 mg/kg, i.p.) was higher than that in controls, whereas the ratio was lower in the liver of rats pretreated with the glutathione-depleting agent, phorone (250 mg/kg, i.p.). These results suggest that 4HN in rat liver is metabolized by the GSH-conjugate system in preference to degradation by ALDH.
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PMID:Effects of aldehyde dehydrogenase and glutathione on the degradation of (E)-4-hydroxy-2-nonenal and N-hexanal in rat liver. 803 11

The influence of genetic variation in alcohol dehydrogenase (ADH; EC 1.1.1.1) and aldehyde dehydrogenase (ALDH; EC 1.2.1.3) on the metabolic pattern of serotonin (5-hydroxytryptamine, 5-HT) in humans was examined from the relative urinary concentrations of the end products 5-hydroxyindole-3-acetic acid (5-HIAA) and 5-hydroxytryptophol (5-HTOL). Healthy Caucasian (Swedish) and Oriental (Chinese) subjects were genotyped for ADH2, ADH3 and ALDH2 by a PCR/SSCP technique. The 5-HTOL/5-HIAA ratios ranged between 0.9-9.4 pmol/nmol (4.4 +/- 1.8, mean +/- SD, n = 143). No significant difference in the 5-HT metabolic pattern was observed between Caucasians and Orientals (4.3 +/- 1.8 and 4.4 +/- 1.8 pmol/nmol, respectively), nor between any of the ADH2, ADH3 and ALDH2 genotypes. Despite the modulatory effects of genetic variation of these enzymes on ethanol metabolism, the present results indicate that the individual isozyme composition of ADH2, ADH3 and ALDH2 is not important for the metabolic pattern of 5-HT.
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PMID:Influence of genetic variation in alcohol and aldehyde dehydrogenase on serotonin metabolism. 803 49

Partial amino acid sequences of the two alcohol dehydrogenases of Bacillus stearothermophilus and the oligonucleotide sequence of a cloned fragment containing the gene for ADH 2334 were determined and compared with the known, derived ADH 1503 amino acid sequence. The two proteins are identical at 244 of 349 positions. ADH 2334 is encoded in a transcription unit containing an aldehyde dehydrogenase.
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PMID:Gene structure and amino acid sequences of alcohol dehydrogenases of Bacillus stearothermophilus. 804 68

Acetaldehyde (AcH) levels in blood samples taken from different zones of the vascular system 2 h after a p.o. dose of ethanol (2.76 g/kg) were studied in UChA (low ethanol consumer) and UChB (high ethanol consumer) rats fed a diet devoid of animal products, diet 1 (D1), and a diet containing fish meal, diet 2 (D2), and in rats pretreated with disulfiram (600 mg/kg p.o.). The results showed that, while there is no significant difference between UChA and UChB rats fed D1 with respect to blood AcH levels and the basal activity of the hepatic mitochondrial high-affinity aldehyde dehydrogenase (AIDH), a significant strain difference was observed in rats fed D2, which induced high blood AcH levels in UChA rats but not in UChB ones. No strain differences were observed in blood ethanol levels in the two groups of rats. When rats fed D1 were pretreated with disulfiram, the raising of AcH blood levels induced by ethanol after disulfiram was significantly higher in UChA than in UChB rats in suprahepatic vein, femoral vein, and tail blood. This difference was concomitant with a greater inhibition of the hepatic mitochondrial high-affinity ADH activity in UChA rats than in UChB ones, whether disulfiram was administered in vivo or in vitro, which excluded the possibility that the strain difference would be caused by a different bioavailability of disulfiram.
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PMID:Effect of diet and disulfiram on acetaldehyde blood levels after ethanol in UChA and UChB rats. 821 84


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