Inducible Aldehyde Dehydrogenases in the Hepatic Cytosol of the Rat
| Autor: | Marios Marselos, Riitta Törrönen, Unto Nousiainen |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Male
Aldehyde dehydrogenase Glucuronates Mitochondria Liver Cytosol/*enzymology Toxicology Aldehyde Cytosol Glucuronates/metabolism medicine Animals ALDH2 Pharmacology chemistry.chemical_classification biology ADH1B Rats Inbred Strains Aldehyde Oxidoreductases Rats Mitochondria Liver/enzymology Enzyme Liver chemistry Biochemistry Aldehyde Oxidoreductases/*metabolism Phenobarbital Enzyme Induction Liver/*enzymology biology.protein Branched-chain alpha-keto acid dehydrogenase complex Phenobarbital/pharmacology medicine.drug |
| Zdroj: | Acta Pharmacologica et Toxicologica. 41:263-272 |
| ISSN: | 0001-6683 |
| Popis: | Rats of the Wistar/Af/Han/Mol/(Han 67) strain have previously been shown to respond in a variable way to phenobarbital treatment, as far as the induction of aldehyde dehydrogenase activity is concerned (Marselos 1976). This biochemical property is genetically determined and concerns the high-Km aldehyde dehydrogenase of the hepatic cytosol. In this study, administration of phenobarbital (1 mg/mo of drinking water, for 1 week) produces a uniform induction of aldehyde dehydrogenase in all rats, when measured with micromolar substrate concentration. The inducible low-Km enzyme of the cytosol is not genetically determined like the high-Km enzyme, and shows a wide specificity for aliphatic as well as for aromatic aldehydes. Despite the inducibility of the cytosolic enzymes, no alterations are found in the mitochondrial aldehyde dehydrogenase activities after phenobarbital treatment. The oxidation of D-glucuronolactone takes place only in the cytosol, and seems to be dependent on the low-Km aldehyde dehydrogenase. This is consistent with NMR studies, which showed that a very minimal amount of D-glucuronolactone is in aldehyde form under the measurement conditions usually applied. Further, the oxidation of D-glucuronolactone is also enhanced by phenobarbital in all rats without a genetic predisposition, and its dose-response curve is very similar to that of the low-Km aldehyde dehydrogenase. Acta Pharmacol Toxicol (Copenh) |
| Databáze: | OpenAIRE |
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