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)

Cellular effects and mobilization of metals by diethyldithiocarbamate (DTC) were studied in primary cultures of rat hepatocytes incubated with lead acetate (PbAc), lead-diethyldithiocarbamate (Pb(DTC)2), cadmium chloride (CdCl2), cadmium-diethyldithiocarbamate (Cd(DTC)2), mercuric acetate (HgAc) and methylmercuric chloride (MeHgCl). In cells pretreated with inorganic Pb, Cd and Hg, the cellular levels of Cd and Pb were somewhat decreased or unchanged after incubation with DTC, while the cellular concentration of Hg was increased. Cells preincubated with MeHgCl showed a marked decrease in cellular Hg concentration upon DTC treatment. In Pb(DTC)2-treated cells the Pb concentration was increased when incubated with DTC, while DTC caused a decrease in Cd concentrations of cells preincubated with Cd(DTC)2. The activity of alcohol dehydrogenase (ADH) in cells incubated with CdCl2, Cd(DTC)2 and HgAc was significantly decreased. In Hg-treated cells the ADH activity was further decreased after incubation with DTC, whereas the activity in Cd-treated cells recovered gradually after incubation with increasing concentrations of DTC. The activity of the enzyme delta-aminolevulinic acid dehydratase (ALAD) was significantly inhibited in cells treated with PbAc and Pb(DTC)2, but could be restored to 80% and to almost 100%, respectively, of control activity after incubation with DTC. It is suggested that, in the absence of excess DTC, a decomposition of Pb(DTC)2 takes place after penetration into the cell, resulting in inhibition of ALAD by the released Pb. In the presence of excessive amounts of DTC, the equilibrium is shifted towards Pb(DTC)2 and Pb in the complex form is not available for ALAD. These studies suggest that DTC decreases cellular effects of Pb and Cd despite unchanged or even increased cellular concentrations of the metals, while the antidotal efficacy of DTC on inorganic Hg toxicity seems to be of low value.
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PMID:Cellular response after mobilization of metals by diethyldithiocarbamate in rat hepatocyte cultures. 217 32

Because ethanol ingestion lowers delta-aminolevulinic acid dehydratase (ALAD) activity in liver and red cells, effects of ethanol and acetaldehyde on ALAD in rat liver cytosol were studied. When added to the assay mix, as little as 0.5 mmol/L acetaldehyde competitively inhibited ALAD even in the presence of dithiothreitol, a sulfhydryl reagent. ALAD activity also fell when undiluted cytosol was incubated at 37 degrees with as little as 0.25 mmol/L acetaldehyde for 8 hours before enzyme assay. Inactivation of ALAD by acetaldehyde was prevented by the metabolic inhibitor NaF but not by the aldehyde dehydrogenase inhibitor cyanamide. Incubation of undiluted cytosol with 20 mmol/L ethanol also decreased ALAD activity, but addition of ethanol to the assay mix had no effect. Ethanol-mediated inactivation of ALAD was reduced by inhibition of alcohol dehydrogenase with 4-methylpyrazole, but ALAD activity was not decreased by incubation of undiluted cytosol with acetate or sorbitol or by addition of acetate to the assay mix. The aldehydic B6 vitamers, pyridoxal and pyridoxal phosphate, also inhibited ALAD activity when added to the assay mix. However, these vitamers increased ALAD activity and decreased acetaldehyde-mediated inactivation of ALAD when incubated for 8 hours with undiluted cytosol. We conclude that (1) acetaldehyde decreases ALAD activity both by competitive inhibition with substrate and by inactivation of enzyme protein and that (2) inactivation of ALAD by acetaldehyde may require nonoxidative metabolism of acetaldehyde. The net pharmacologic effect of B6 vitamers on ALAD activity and on inactivation of ALAD by acetaldehyde remains to be determined.
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PMID:delta-Aminolevulinic acid dehydratase in rat liver: studies on the effects of ethanol, acetaldehyde, and B6 vitamers. 239 40

The influence of chelating agents (1 mmol/kg/day X 6,i.p.) on trace metal mobilization and activities of certain metalloenzymes was investigated in rats. Calcium disodium ethylenediamine tetraacetate (CaNa2EDTA) and calcium trisodium diethylenetriamine pentaacetate (CaNa3DTPA) enhanced urinary excretion of Zn, while sodium 2,3-dimercaptopropane-1-sulfonate (NaDMPS) and sodium diethyldithiocarbamate (NaDDC) increased that of Cu. The activity of Zn-metalloenzymes-blood delta-aminolevulinic acid dehydratase (delta-ALA-D), plasma alkaline phosphatase (ALP) and that of Cu-metalloenzyme-plasma amine oxidase was decreased as a consequence of chelation therapy. However, hepatic levels of delta-ALA-D, ALP and alcohol dehydrogenase remained unaffected by chelation. The activity of hepatic Fe-metalloenzyme-catalase was increased by polyaminocarboxylic acids and lowered by thiol chelators. The metal chelators decreased the hepatic glutathione levels.
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PMID:Influence of metal chelators on metalloenzymes. 361 94