title: Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the brain 2-oxo acid dehydrogenases are inactivated despite unchanged coenzyme levels.
abstract: Thiamine-dependent changes in alcoholic brain were studied using a rat model. Brain thiamine and its mono- and diphosphates were not reduced after 20 weeks of alcohol exposure. However, alcoholism increased both synaptosomal thiamine uptake and thiamine diphosphate synthesis in brain, pointing to mechanisms preserving thiamine diphosphate in the alcoholic brain. In spite of the unchanged level of the coenzyme thiamine diphosphate, activities of the mitochondrial 2-oxoglutarate and pyruvate dehydrogenase complexes decreased in alcoholic brain. The inactivation of pyruvate dehydrogenase complex was caused by its increased phosphorylation. The inactivation of 2-oxoglutarate dehydrogenase complex (OGDHC) correlated with a decrease in free thiols resulting from an elevation of reactive oxygen species. Abstinence from alcohol following exposure to alcohol reactivated OGDHC along with restoration of the free thiol content. However, restoration of enzyme activity occurred before normalization of reactive oxygen species levels. Hence, the redox status of cellular thiols mediates the action of oxidative stress on OGDHC in alcoholic brain. As a result, upon chronic alcohol consumption, physiological mechanisms to counteract the thiamine deficiency and silence pyruvate dehydrogenase are activated in rat brain, whereas OGDHC is inactivated due to impaired antioxidant ability.
authors.affiliation: A. V. Palladin Institute of Biochemistry, NAS of Ukraine, Kiev, Ukraine.
authors.forename: Yulia M
authors.initials: YM
authors.lastname: Parkhomenko
authors.forename: Pavel A
authors.initials: PA
authors.lastname: Kudryavtsev
authors.forename: Svetlana Yu
authors.initials: SY
authors.lastname: Pylypchuk
authors.forename: Lilia I
authors.initials: LI
authors.lastname: Chekhivska
authors.forename: Svetlana P
authors.initials: SP
authors.lastname: Stepanenko
authors.forename: Andrej A
authors.initials: AA
authors.lastname: Sergiichuk
authors.forename: Victoria I
authors.initials: VI
authors.lastname: Bunik
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism*; D003067:Coenzymes / Q000378:metabolism*; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010766:Phosphorylation; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013835:Thiamine Pyrophosphate / Q000378:metabolism*
chemical_list: D003067:Coenzymes; D011768:Pyruvate Dehydrogenase Complex; D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D007655:Ketoglutarate Dehydrogenase Complex; D013835:Thiamine Pyrophosphate