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)

Alcohol (ethanol) use during pregnancy can produce a wide spectrum of effects in the developing embryo/fetus that are dependent on the maternal drinking pattern. The effects of chronic ethanol exposure on the developing conceptus are reviewed with primary focus on ethanol teratogenesis, manifesting in the human as the fetal alcohol syndrome or fetal alcohol effects. The effects of acute ethanol exposure on the near-term fetus are described, including suppressed fetal breathing movements, electrocorticographic (ECoG) activity and electrooculographic (EOG) activity. The ethanol-induced suppression of fetal breathing movements is a very sensitive index of acute exposure of the near-term fetus to ethanol, and appears to involve a direct mechanism of action rather than an indirect mechanism involving suppression of electrocortical activity. The disposition of ethanol and its pharmacologically active proximate metabolite, acetaldehyde, and the activity of alcohol dehydrogenase and aldehyde dehydrogenase in the near-term maternal-fetal unit are described, and a pharmacokinetic model is proposed. The effects of short-term ethanol exposure on the near-term fetus include the development of tolerance to the ethanol-induced suppression of fetal breathing movements, low-voltage ECoG activity and EOG activity. The development of tolerance occurs more rapidly to the latter two fetal biophysical activities. The mechanism of tolerance development appears to be pharmacodynamic (functional) in nature, as there is no increase in the rate of ethanol elimination from the maternal-fetal unit. The role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of fetal breathing movements is described. In the near-term fetus, there is a direct relationship between fetal blood ethanol concentration and fetal plasma PGE2 concentration, and an inverse relationship between the incidence of fetal breathing movements and each of fetal plasma and fetal cerebrospinal fluid (CSF) PGE2 concentrations. Indomethacin, a PG synthetase inhibitor, selectively blocks and reverses the ethanol-induced suppression of fetal breathing movements. These data support the postulates that the ethanol-induced suppression of fetal breathing movements is mediated by increased PGE2 concentration in the near-term fetus and that the ability of indomethacin to antagonize the ethanol-induced suppression of fetal breathing movements is due to its biochemical action to decrease fetal PGE2 concentration.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of alcohol (ethanol) on the fetus. 187 37

SU-88 [2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone] inhibited the activity of the prostaglandin (PG)-metabolizing enzyme, 15-hydroxy-PG-dehydrogenase (15-OH-PG-DH), in a cytoplasmic fraction of gastric mucosa. This compound had no effect on the PG synthetase of bovine seminal vesicle microsomes and lactate dehydrogenase in rat liver. The 15-OH-PG-DH activity of gastric mucosa was not influenced by a specific inhibitor of alcohol dehydrogenase, 4-methylpyrazole. Carbenoxolone (CBX) also inhibited 15-OH-PG-DH activity. The IC50 values for SU-88 and CBX were approximately 20 and 40 microM respectively. SU-88 inhibited 15-OH-PG-DH activity uncompetitively or competitively according to whether PGE1 or NAD was used as substrate. CBX inhibited competitively the activity of this enzyme for both substrates. After the addition of SU-88 or CBX to the incubation medium of gastric mucosa, the PGE2 level of the medium was increased significantly while that of the tissue remained unchanged. These results indicate that SU-88 specifically inhibited 15-OH-PG-DH activity and suggest that 15-OH-PG-DH activity regulates the level of PGs in gastric mucosa and may have an anti-ulcer influence.
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PMID:Effect of 2'-carboxymethoxy-4,4'-bis(3-methyl-2-butenyloxy)chalcone (SU-88) on prostaglandin metabolism in hog gastric mucosa. 646 76