Disease relevance of Adh1

• Age did not influence the specific activity of hepatic or gastric alcohol dehydrogenase, whereas the activity was significantly decreased with age in the liver (p less than 0.05) and in the stomach (p less than 0.001) when related to body weight [1].
• Kinetic properties of alcohol dehydrogenase in hepatocellular carcinoma and normal tissues of rat [2].
• By contrast, alcohol dehydrogenase from the well-differentiated Morris hepatoma 5123C had properties similar to those of the liver enzyme [2].
• Sham-operated rats injected with 100 micrograms thyroxine/kg/day, which induced hyperthyroidism, showed a 30% decrease in liver and a 40% decrease in kidney alcohol dehydrogenase activity compared with sham-operated rats injected with vehicle [3].
• Protein deficiency alone was associated with reduced ethanol clearance and decreased activity of hepatic alcohol dehydrogenase and the microsomal ethanol-oxidizing system [4].

Psychiatry related information on Adh1

• Influence of the immunization against heterologous alcohol dehydrogenase on liver alcohol dehydrogenase isozymes and alcohol abuse of rats [5].
• Formation of HBO by ADH was dependent upon reaction time, protein concentration, substrate concentration, and the presence of NAD [6].
• We have identified the retinoid-synthesizing enzymes involved in this process, retinaldehyde dehydrogenase-2 and class IV alcohol dehydrogenase, only the former is downregulated in patients with Alzheimer's disease [7].
• Electrophysiological and biochemical studies demonstrated that pyrazole, an inhibitor of alcohol dehydrogenase and a proposed therapeutic agent for treatment of alcoholic intoxication, activated and blocked the N-methyl-D-aspartate (NMDA) receptor and did not interact significantly with the end-plate nicotinic acetylcholine receptor (AChR) [8].
• Differences in the amount of alcohol dehydrogenase (ADH) expressed in liver could play a role in altering ethanol metabolic rates and thus influence alcohol consumption [9].

High impact information on Adh1

• This negligible metabolism was predictable from the low affinity of gastric ADH for ethanol [10].
• In contrast, gastric ADH has a high affinity for octanol, and 66% of this compound was metabolized during gastric absorption [10].
• Compared with the liver, FAEE synthase activity in the pancreas is greater, whereas that of ADH is much less [11].
• Inhibition of ADH by 4MP prevented ethanol-induced cell activation [12].
• These changes were prevented by the antioxidant vitamin E. Stellate cells exhibited ethanol-inducible ADH activity [12].

Chemical compound and disease context of Adh1

• Alcohol dehydrogenase from Morris hepatoma 7288ctc, a fast-growing, poorly differentiated tumor, had properties similar to those found with the Becker-H-252 tumor, including a high Km for ethanol and acetaldehyde and the absence of substrate inhibition [2].
• The effect of lipopolysaccharide (LPS), the endotoxin component of Gram-negative bacteria, was determined on liver ADH [13].
• It is generally believed that acrolein, generated out of allyl alcohol by cytosolic alcohol dehydrogenase, is responsible for this toxicity [14].
• Induction of alcohol dehydrogenase activity and mRNA in hepatoma cells by dexamethasone [15].
• The H35 hepatoma cell line studied was first evaluated for enzymes known to play important roles in the metabolism of 4-HNE and were found to possess activities for glutathione S-transferase, aldehyde dehydrogenase (ALDH), and alcohol dehydrogenase of 24.00 +/- 1.12, 3 [16].

Biological context of Adh1

• Because the ADH promoter contains two canonical sterol response element (SRE) sites (-63 to -53 and -52 to -40 relative to the transcription start site), electrophoretic mobility shift assays were conducted using an ADH-specific SRE site [17].
• Abundant levels of class-III alcohol-dehydrogenase (glutathione-dependent formaldehyde dehydrogenase) mRNA were present in all tissues analyzed, reflecting the general need for scavenging of formaldehyde in physiological cytoprotection [18].
• Ethanol induction of class I alcohol dehydrogenase expression in the rat occurs through alterations in CCAAT/enhancer binding proteins beta and gamma [19].
• These data provide the first evidence for the mechanism by which ethanol regulates rat hepatic Class I ADH gene expression in vivo [19].
• Cis-acting elements within the proximal promoter region of the ADH gene were studied by electrophoretic mobility shift assay (EMSA) [19].

Anatomical context of Adh1

• In contrast, class I ADH, primarily responsible for ethanol metabolism, was found only in the cytoplasm of hepatocytes [20].
• Hybridization revealed the pattern of occurrence of class-II alcohol-dehydrogenase mRNA to be unique, with transcripts only in the liver, duodenum, kidney, stomach, spleen and testis [18].
• Expression, localization and potential physiological significance of alcohol dehydrogenase in the gastrointestinal tract [21].
• By means of microdissection and ultrathin-layer gel electrophoresis, alcohol dehydrogenase isoenzyme activity was determined quantitatively in the various layers of the vaginal mucous membrane [22].
• After intoxication with a sublethal dose, the ADH activity measured with these naphthaldehydes and ALDH activities in the stomach and small intestine were significantly decreased [23].

Associations of Adh1 with chemical compounds

• In this study, we further explore the molecular mechanism for ethanol-induced ADH expression during the UEC pulse in adult male rats fed ethanol by total enteral nutrition for 21-30 days [17].
• ADH3 (identical to glutathione-dependent formaldehyde dehydrogenase) is clearly the ancestral ADH form and S-hydroxymethylglutathione is the main physiological substrate, but the enzyme can still oxidize ethanol at high concentrations [24].
• It also contains an additional cysteine in the highly variable region from aa residues 108-125 which may account for the unusual lability of rat ADH compared with ADH from other species [25].
• Effect of dihydrotestosterone on rat liver alcohol dehydrogenase activity [26].
• In this study, the effect of dihydrotestosterone, which is a more potent androgen than testosterone in the rat, was determined on liver alcohol dehydrogenase and ethanol elimination in the castrated rat [26].

Physical interactions of Adh1

• Alcohol dehydrogenase-coupled spectrophotometric assay of epoxide hydratase activity [27].

Regulatory relationships of Adh1

• Post-transcriptional regulation of sterol regulatory element-binding protein-1 by ethanol induces class I alcohol dehydrogenase in rat liver [17].
• Growth hormone (GH) enhances rat liver alcohol dehydrogenase (ADH) due to an increase in enzyme synthesis, which is mediated at the level of transcription [28].
• Evidence was provided through kinetic studies that the epsilon-Gua adducts are formed primarily from 2-haloxiranes; consistent with this view, epoxide hydrolase inhibited the formation of N2,3-epsilon-Gua from vinyl chloride but alcohol dehydrogenase did not [29].
• Alcohol dehydrogenase (ADH) is enhanced separately by epinephrine and by glucagon in primary rat hepatocyte culture [30].

Other interactions of Adh1

• In hypophysectomized rats, in which the ADH protein increased by approximately 6-fold, the nuclear form of SREBP-1 decreased by approximately 7-fold [17].
• Sorbitol dehydrogenase: cDNA coding for the rat enzyme. Variations within the alcohol dehydrogenase family independent of quaternary structure and metal content [31].
• Endocytosis of lactate dehydrogenase M4 exhibited saturation kinetics (Km = 0.8 microM) and was competitively inhibited by mitochondrial and cytosolic malate dehydrogenase, alcohol dehydrogenase, adenylate kinase, and creatine kinase MM, enzymes which are rapidly cleared in vivo [32].
• Hepatic estrogen receptor status and the activity of alcohol dehydrogenase, an androgen-sensitive protein, were measured [33].
• Under these conditions there were no apparent effects on blood concentrations of ethanol and acetaldehyde nor on activities of hepatic alcohol dehydrogenase, aldehyde dehydrogenase, glutathione-dependent detoxifying enzymes, superoxide dismutase or catalase [34].

Analytical, diagnostic and therapeutic context of Adh1

• Castration was previously demonstrated to result in an increase in liver alcohol dehydrogenase and in rates of ethanol elimination in male rats [26].
• The class II enzyme has now been purified to homogeneity by ion exchange and affinity chromatography and, except for an isoelectric point of 7.7, closely resembles human class III ADH [35].
• 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 [5].
• Thyroidectomy resulted in a marked increase in liver alcohol dehydrogenase activity [36].
• Three isoenzymes of alcohol dehydrogenase activity were demonstrated in thyroidectomized animals by starch gel electrophoresis, as compared with two in sham-operated control animals [36].

References