Brain pyruvate oxidation in experimental thiamin-deficiency encephalopathy.
Pyrithiamine-induced thiamin deficiency has been used in rat as an experimental form of Wernicke-Korsakoff encephalopathy, a disease associated with chronic alcoholism. Although the main etiological factor is known to be the lack of thiamin, the biochemical mechanisms involved in the pathogenesis remain unclear. Thiamin-dependent enzymes were studied in brain mitochondria: alpha-ketoglutarate dehydrogenase activity exhibited 40% reduction, whereas pyruvate dehydrogenase did not change significantly. Polarographic recordings of mitochondrial respiration revealed a decreased State 3, when using pyruvate/malate, alpha-ketoglutarate or glutamine as a substrate, but the respiration rates remained unchanged with glutamate or succinate. This fall in pyruvate oxidation may be due to the impairment of alpha-ketoglutarate dehydrogenase, which follows pyruvate dehydrogenase in the metabolic pathway. A time course of lactate concentration showed dramatic increases in thalamus, mid brain, hypothalamus and colliculli, consistent with the anatomopathological findings. No increases were found before the onset of neurological symptoms.
Munujos
P
P
Department of Biochemistry and Molecular Biology, Universitat Autònoma de Barcelona, Hospital de Sant Pau de Barcelona, Catalonia, Spain. petraki_munujos@servicom.es
Coll-Cantí
J
J
Beleta
J
J
González-Sastre
F
F
Gella
F J
FJ
D000425:Alcohol Amnestic Disorder / Q000209:etiology*; D000818:Animals; D001921:Brain / Q000201:enzymology*; D001923:Brain Chemistry; D005260:Female; D007031:Hypothalamus / Q000737:chemistry; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008636:Mesencephalon / Q000737:chemistry; D008928:Mitochondria / Q000201:enzymology; D010101:Oxygen Consumption; D011745:Pyrithiamine; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D019289:Pyruvic Acid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013379:Substrate Specificity; D013788:Thalamus / Q000737:chemistry; D013832:Thiamine Deficiency / Q000139:chemically induced / Q000201:enzymology*; D013997:Time Factors; D014899:Wernicke Encephalopathy / Q000209:etiology*
D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D011745:Pyrithiamine; D019289:Pyruvic Acid; D007655:Ketoglutarate Dehydrogenase Complex