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

Ethanol is easily absorbed from the intestine and diffuses quickly throughout body water. The bulk of ethanol is metabolized in the liver, where alcohol dehydrogenase, a complex mixture of isoenzymes, oxidizes ethanol to acetaldehyde. Ethanol abuse produces functional and structural changes in the gastrointestinal tract, such as in the stomach, small intestine, liver, and pancreas. Accumulating evidence suggests direct toxicity of ethanol and possibly of acetaldehyde. Fatty liver, alcoholic hepatitis, liver cirrhosis, acute and chronic gastritis, deranged structure and function of the small intestine, acute and chronic pancreatitis, and pancreatic lithiasis are some of the sequelae of ethanol abuse. Recent investigations have enhanced our understanding of the functional and structural changes of the gastrointestinal tract produced by the abuse of ethanol.
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PMID:Ethanol, the liver, and the gastrointestinal tract. 719 92

The gastrointestinal tract is a major site of alcohol dehydrogenase (ADH) activity in humans and rodents. Because class I ADH (ADH-I) and class IV ADH (ADH-IV), but not class III ADH (ADH-III), function as retinol dehydrogenases in vitro and may thus participate in retinoid signaling needed for epithelial differentiation, the aim of this study was to determine the localization of these enzymes along the gastrointestinal tract. Specific antibodies were used to examine the tissue distribution of all three known classes of mouse ADH by Western blotting, and cellular localization was determined by immunohistochemistry. ADH-I was detected primarily in the intestine, liver, kidney, adrenal, and uterus, with detection of ADH-III in all tissues examined, and detection of ADH-IV primarily in the esophagus, stomach, adrenal, skin, ovary, and epididymis. Along the gastrointestinal tract, ADH-III was not specifically localized, whereas ADH-I was localized exclusively in the villus epithelium of the small intestine and absorptive epithelium of the large intestine, with ADH-IV being localized exclusively in the basal and suprabasal epithelial cells of the esophagus and gastric pit surface epithelium of the stomach. The ADH localization patterns observed are consistent with ADH-I and ADH-IV, but not ADH-III, functioning physiologically in retinol metabolism needed for epithelial differentiation. Our results further suggest that the functions of ADH-I and ADH-IV are regionally restricted to the lower and upper components, respectively, of the gastrointestinal epithelium, a finding that may relate to the different efficiencies of these two enzymes for retinol oxidation, as well as to the different susceptibilities of the upper and lower digestive tracts for ethanol-induced cancers.
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PMID:Regional restriction of alcohol/retinol dehydrogenases along the mouse gastrointestinal epithelium. 939 22

Mammalian alcohol dehydrogenases ADH1 (class I ADH) and ADH4 (class IV ADH) function as retinol dehydrogenases contributing to the synthesis of retinoic acid, the active form of vitamin A involved in growth and development. Xenopus laevis ADH1 and ADH4 genes were isolated using polymerase chain reaction primers corresponding to conserved motifs of vertebrate ADHs. The predicted amino acid sequence of Xenopus ADH1 was clearly found to be an ortholog of ADH1 from the related amphibian Rana perezi. Phylogenetic tree analysis of the Xenopus ADH4 sequence suggested this enzyme is likely to be an ADH4 ortholog, and this classification was more confidently made when based also on the unique expression patterns of Xenopus ADH1 and ADH4 in several retinoid-responsive epithelial tissues. Northern blot analysis of Xenopus adult tissues indicated nonoverlapping patterns of ADH expression, with ADH1 mRNA found in small intestine, large intestine, liver, and mesonephros and ADH4 mRNA found in esophagus, stomach, and skin. These nonoverlapping tissue-specific patterns are identical to those previously observed for mouse ADH1 and ADH4, thus providing further evidence that Xenopus ADH1 and ADH4 are orthologs of mouse ADH1 and ADH4, respectively. During Xenopus embryonic development ADH1 mRNA was first detectable by Northern blot analysis at stage 35, whereas ADH4 mRNA was undetectable through stage 47. Whole-mount in situ hybridization indicated that ADH1 expression was first localized in the pronephros during Xenopus embryogenesis, thus conserved with mouse embryonic ADH1 which is first expressed in the mesonephros. ADH4 expression was not detected in Xenopus embryos by whole-mount in situ hybridization but was localized to the gastric mucosa of the adult stomach, a property shared by mouse ADH4. Conserved expression of ADH1 and ADH4 in retinoid-responsive epithelial tissues of amphibians and mammals argue that these enzymes may perform essential retinoid signaling functions during development of the pronephros, mesonephros, liver, and lower digestive tract in the case of ADH1 and in the skin and upper digestive tract in the case of ADH4.
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PMID:Alcohol dehydrogenases in Xenopus development: conserved expression of ADH1 and ADH4 in epithelial retinoid target tissues. 982 62

Efficiency of nutrient utilization is high in neonates with normal birth weights but is reduced in those with intrauterine growth restriction (IUGR). However, the underlying mechanisms are largely unknown. This study was conducted with the piglet model and proteomics technology to test the hypothesis that IUGR affects expression of key proteins that regulate growth and development of the small intestine, liver, and muscle, the major organs involved in the digestion, absorption, and metabolism of dietary nutrients. Jejunum, liver, and gastrocnemius muscle were obtained from IUGR and normal birth-weight piglets at birth for analysis of proteomes using the 2-dimensional-PAGE MS technology. The results indicate that IUGR decreased the levels of proteins that regulate immune function (immunoglobulins and annexin A1), oxidative defense (peroxiredoxin 1, transferrin, and zeta-crystallin), intermediary metabolism (creatine kinase, alcohol dehydrogenase, L-lactate dehydrogenase, prostaglandin F synthase, apolipoprotein AI, catecho O-methyltransferase, and phosphoglycerate kinase 1), protein synthesis (eukaryotic translation initiation factor-3), and tissue growth (beta-actin, desmin, and keratin 10) in a tissue-specific manner. In addition, IUGR increased the levels of proteins that are involved in proteolysis (proteasome alpha-5 and alpha-1 subunits), response to oxidative stress (scavenger-receptor protein and alpha-1 acid glycoprotein), and ATP hydrolysis (F1-ATPase). These novel findings suggest that cellular signaling defects, redox imbalance, reduced protein synthesis, and enhanced proteolysis may be the major mechanisms responsible for abnormal absorption and metabolism of nutrients, as well as reduced growth and impaired development of the small intestine, liver, and muscle in IUGR neonates.
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PMID:Intrauterine growth restriction affects the proteomes of the small intestine, liver, and skeletal muscle in newborn pigs. 1815 5