Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vivo and in vitro effects of d-amphetamine on the specific activities of endogenous liver alcohol-(L-ADH) and aldehyde dehydrogenase (L-ADH) were studied using rat and mouse liver enzyme preparations. d-Amphetamine, 10(-4)M, noncompetitively inhibited rat and mouse L-ALDH in vitro. Mitochondrial L-ALDH was not affected by d-amphetamine in vivo and in vitro in both species studied. A noncompetitive inhibition of mouse L-ADH, occurred in vivo 16 hr after administration of d-amphetamine, 4 mg/kg, IP. A moderate, but not significant decline in specific activity of rat L-ADH was determined after injection of d-amphetamine, 4 mg/kg IP, showed a significant decrease in their blood and brain content of exogenously administered ethanol from corresponding saline-treated controls for the 60 min and 90 min periods after ethanol administration, respectively. The results show species differences in d-amphetamine action on liver enzymes studied and indicate that d-amphetamine can interfere in the metabolism of ethanol.
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PMID:d-Amphetamine and ethanol: a drug-drug interaction study. 31 82

Both alcohol dehydrogenase (ADH) and the two isoenzymes of aldehyde dehydrogenase (ALDH-I-NAD+ and ALDH-II-NAD+) were first detected in foetal rat liver about 5 days before birth. All enzymes developed gradually and showed no abrupt increases in activity. The specific activities of ALDH-I-NAD+ and ALDH-II-NAD+ in the mitochondrial fractions, ALDH-II-NAD+ in the microsomal fractions and ADH in liver homogenates all produced a major percentage of the adult activity within a month, whereas the total activities increased over a longer part of the developmental period.
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PMID:Developmental patterns of alcohol dehydrogenase and aldehyde dehydrogenases in homogenates and subcellular fractions of rat liver. 39 12

The ontogenetic development of the enzymes alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenases (ALDH I and II) was followed in rats. ADH could be detected just before birth and increased gradually to reach 82% of adult values at 47 days. ALDH I and II were present from day 15 of gestation, increased rapidly at birth, and reached 80-90% adult values at 47 days. The ratio between ALDH and ADH activities decreased gradually during ontogenesis. The relative subcellular distribution of all enzymes was identical before birth, 7 days after birth and in adults. The placental activities of ADH and ALDH I and II were studied at 15 and 20 days of pregnancy. ADH could not be detected in placentas. Low activities of ALDH I and II were present in placentas studied at 15 days of gestation, and still lower activities were found in placenta at 20 days.
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PMID:Activity of alcohol dehydrogenase and acetaldehyde dehydrogenases in the liver and placenta during the development of the rat. 63 76

The behavioral and biochemical effects of amantadine hydrochloride (ATD) on some ethanol (ETOH) mediated responses in rats and mice were studied. Administration of ATD, 0.5 mM/kg IP, prior to a narcotic dose of ETOH significantly decreased the central depressant action of ETOH, as measured by the duration of ETOH-produced narcosis in mice. The time required for the onset of ETOH-narcosis was significantly delayed in ATD-treated mice compared to controls. Analyses of whole blood and brain ETOH concentrations showed that ATD-treatment prior to ETOH significantly reduced brain content of ETOH from saline-pretreated mice at the time of onset of ETOH narcosis as well as 30 min after ETOH injection without concomitant change in blood ETOH concentrations at the respective time intervals. Administration of ATD 0.5mM/kg IP, reduced voluntary intake of ETOH by rats voluntarily selecting 5% ETOH solution over water as the drinking fluid. There were no changes in cytoplasmic rat liver alcohol dehydrogenase (L-ADH) and mitochondrial aldehyde dehydrogenase (L-ALDH) activities in rats maintained on water or 5% ETOH as the drinking fluid and administered ATD, 0.5 mM/kg IP, once or identical dose once daily for six consecutive days. However, ATD produced in vitro non-competitive inhibiton of both L-ADH and L-ALDH at a concentration range between 10(-3) M and 3 x 10(-3) M assay mixture. The results indicate the potency of ATD in negating ETOH-mediated responses measured and suggest for a possible clinical trial for ATD in the management of alcoholic patients provided it is devoid of disulfiram-like reaction in man.
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PMID:Antagonism of ethanol-evoked responses by amantadine: a possible clinical application. 67 56

The present study evaluates the possible relationship between certain biogenic amine metabolites-produced changes in voluntary drinking of ethyl alcohol (ET) solution by the rat and their in vivo effects on the enzymes primarily involved in the hepatic metabolism of ET, i.e., liver alcohol-(L-ADH) and aldehyde dehydrogenase (L-ALDH). In experiments on voluntary intake of ET solution by the rat, compounds selected were injected, 0.5 mM/kg, IP. Administration of vanillylmandelic acid (VMA) and 5-hydroxyindoleacetic acid (5HIAA) and homovanillic acid (HVA) markedly reduced ET drinking. Similar significant effects were seen after administration of the neutral metabolites of the biogenic amines tested, after injection of metanephrine or 3-methoxy-4-hydroxyphenylpyruvic acid. Threodihydroxyphenylserine but not L-dopa reduced ET intake by the rat. Treatment with peripheral decarboxylase inhibitors, i.e., carbidopa, 50 mg/kg, IP, significantly reduced ET drinking as contrasted with nonsignificant decline in ET consumption following benserazide, 500 mg/kg, IP. In the biochemical study, short-term administration of the compounds selected produced varied effects on L-ADH and L-ADH. It is suggested that alteration of hepatic ADH by the compounds tested might account for the observation reduced ET drinking thereby, indicating the contribution of peripheral sources rather than central factors in mediating the behavioral effects studied.
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PMID:Voluntary drinking of ethanol by the rat: biogenic amines and possible underlying mechanism. 71 86

To clarify the regional capacity of the brain to oxidize biogenic aldehydes and ethanol-derived acetaldehyde, a quantitative immunohistochemical study of the microregional and cellular expression of low Km mitochondrial aldehyde dehydrogenase (mALDH; EC 1.2.1.3) in the rat central nervous system was undertaken, using antiserum raised in rabbit against low-Km aldehyde dehydrogenase purified from rat liver mitochondria. mALDH-specific immunoreactivity (IR) was observed to various extent in the majority of structures in all brain and spinal cord areas. Staining was strong in the extranuclear cytoplasm of neuronal and glial cell bodies but less pronounced in their processes and terminals, the conducting tracts, white matter and neuropile and in blood vessels. Immunostaining density was 2 to 3 times higher in neuronal perikarya as compared with neuropile. mALDH-positive neurons were found in all brain regions, being strongest in the inferior olive and hippocampus stratum pyramidale and weakest in substantia nigra. The percentage of morphologically identifiable ALDH-positive neurons ranged from 40% in the arcuate hypothalamic nucleus to 88% in the cerebellar Purkinje cells. A comparison of the heterogeneous expression of mALDH in various rat CNS regions and cells, as observed in the present study, with the corresponding previously published distributions of the potential acetaldehyde-producing enzymes ADH and cytochrome P450 2E1 indicates major differences, which may help in understanding potential acetaldehyde-mediated CNS effects of ethanol. Knowledge of the regional distribution of high-affinity aldehyde dehydrogenase should also throw light on the neurophysiological role of local regulation of the metabolism of biogenic aldehydes in the brain.
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PMID:Regional distribution of low-Km mitochondrial aldehyde dehydrogenase in the rat central nervous system. 147 72

The metabolism of trans,trans-muconaldehyde (MA), a highly reactive alpha,beta-unsaturated dialdehyde, was examined in vitro using purified yeast alcohol and aldehyde dehydrogenases (ADH and ALDH, respectively). In the presence of NAD(+)-fortified ALDH, the mono-oxidation product (acid/aldehyde) was the primary metabolite formed with trace amounts of the dioxidation product (trans,trans-muconic acid). In NADH-fortified reactions with ADH, both the mono- and direduction products (hydroxy/aldehyde and dihydroxy, respectively) were readily detected. Oxidation and reduction products of MA were formed in incubates containing both dehydrogenases together with either NAD+ or NADH. Unexpectedly, an additional metabolite was detected, which was a major product in both NAD(+)- and NADH-fortified systems containing ALDH and ADH in combination and whose formation could be inhibited by pyrazole (an ADH inhibitor). ALDH-mediated oxidation of a synthetic standard of the hydroxy/aldehyde derivative of MA resulted in formation of this new metabolite, which was also a major product formed by rat hepatocytes incubated with MA. Using HPLC/photodiode array detection, the new metabolite was found to cochromatograph and have a uv spectrum identical to that of a synthetic standard of the hydroxy/acid derivative of MA. The metabolite was confirmed as the hydroxy/acid derivative of MA after preparative HPLC, TMS derivatization, and GC/MS analysis. The hydroxy/acid metabolite was not formed during ADH-mediated reduction of the mono-oxidation product of MA, suggesting that this metabolite was formed by yeast dehydrogenases via a primary reduction of MA and subsequent oxidation of the hydroxy/aldehyde to the hydroxy/acid. These data show that the hydroxy/acid derivative is a novel metabolite of MA, which arises from the interaction of both oxidative and reductive routes of metabolism.
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PMID:Metabolism of trans,trans-muconaldehyde by aldehyde and alcohol dehydrogenases: identification of a novel metabolite. 158 67

1. Gossypol, an antifertility ingredient of the cotton plant, altered specific activity of mouse liver alcohol dehydrogenase (L-ADH) and subcellular aldehyde dehydrogenase (L-ALDH) in mice of both sexes. 2. Intraperitoneal injection of a single gossypol dose, 50 mg/kg, inhibited both male and female L-ADH and cytoplasmic L-ALDH from saline controls 21 hr after drug treatment. 3. Gossypol inhibited female but not male mouse mitochondrial L-ALDH isoenzymes. 4. Gossypol-produced enzyme inhibition was determined as noncompetitive. 5. The results suggest gender-dependent sensitivity of mitochondrial L-ALDH to the gossypol inhibition. A toxic metabolic interaction between ethanol and gossypol has been indicated which suggests the contraindication of alcoholic beverages during gossypol use.
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PMID:Effect of gossypol on kinetics of mouse liver alcohol and aldehyde dehydrogenase. 193 90

Mice (Mus musculus) from three genetic strains with variable responses to ethanol challenge (BALB/c, C57BL/6J and 129/ReJ) were used to evaluate the effect of ethanol feeding on hepatic mRNA specific to the two primary enzymes of ethanol metabolism; alcohol dehydrogenase (ADH; E.C. 1.1.1.1) and aldehyde dehydrogenase (ALDH; E.C. 1.2.1.3). Adh-1 (ADH) and Ahd-2 (ALDH) specific mRNA were evaluated on the livers of ethanol-fed mice and from their age, sex and genotype matched controls (using an isocaloric liquid diet). C57BL/6J (alcohol resistant) mice show a significant (approx. 200%) increase in ADH-1 mRNA levels after ethanol treatment, compared to their matched controls. BALB/c (alcohol sensitive) mice have approximately a 20% increase with ethanol treatment while 129/ReJ (alcohol sensitive) mice show a slight reduction in the ADH-1 specific mRNA following ethanol feeding. A strain-specific pattern is also apparent in the AHD-2 mRNA as a result of ethanol feeding in the experimental animals. C57BL/6J mice have an increase and BALB/c mice show no apparent change in the AHD-2 mRNA. 129/ReJ mice fed an ethanol diet, on the other hand, appear to have a decrease in the level of AHD-2 hepatic mRNA as compared to their matched controls. The relative mRNA levels of the two genes correlate well with the respective enzyme activity levels, but for mice on the control diet only. Ethanol feeding, which causes an apparent reduction in hepatic ADH enzyme activity in BALB/c and 129/ReJ and an apparent increase in ALDH activity in C57BL/6J (under the experimental protocols used) also alters the mRNA levels specific to the two genes. However, changes in the mRNA levels after ethanol feeding cannot be directly related to the changes seen in enzyme activity. The observed steady state level of AHD-2 mRNA and the increase in ALDH activity after ethanol feeding, which is unique to C57BL/6J mice, is expected to offer a faster clearance (metabolism) of acetaldehyde, the toxic metabolite, and may be responsible for, or contribute to, the relative resistance of this strain to ethanol.
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PMID:Studies with cDNA probes on the in vivo effect of ethanol on expression of the genes of alcohol metabolism. 222 72

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


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