Thiamine-dependent enzyme changes in the brains of alcoholics: relationship to the Wernicke-Korsakoff syndrome.
Chronic alcoholism results in thiamine deficiency as a consequence of poor nutrition, impaired absorption, and decreased phosphorylation to the enzyme cofactor form of the vitamin, thiamine pyrophosphate (TPP). Results of this study demonstrate significant reductions of TPP-dependent enzymes [pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase (alpha KGDH), and transketolase] in autopsied cerebellar vermis samples from alcoholic patients with the clinical and neuropathologically confirmed diagnosis of Wernicke-Korsakoff Syndrome (WKS). Enzyme activities in brain samples from alcoholics without WKS were within normal limits and activities of a nonthiamine-dependent enzyme, glutamate dehydrogenase, were not significantly different from control values in brain samples from alcoholics with or without WKS. These findings provide evidence, for the first time, of a direct implication of TPP-related metabolic processes in the pathogenesis of WKS. Decreased activities of alpha KGDH could be the trigger for a sequence of metabolic events resulting in energy compromise, and ultimately neuronal death in this syndrome.
Butterworth
R F
RF
Neuroscience Research Unit, Hôpital Saint-Luc (University of Montreal), Quebec, Canada.
Kril
J J
JJ
Harper
C G
CG
D000328:Adult; D000368:Aged; D000425:Alcohol Amnestic Disorder / Q000201:enzymology / Q000473:pathology*; D000437:Alcoholism / Q000201:enzymology / Q000473:pathology*; D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D001921:Brain / Q000201:enzymology / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology; D005260:Female; D006501:Hepatic Encephalopathy / Q000201:enzymology / Q000473:pathology; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D013832:Thiamine Deficiency / Q000201:enzymology / Q000473:pathology*; D014174:Transketolase / Q000378:metabolism*; D014899:Wernicke Encephalopathy / Q000201:enzymology / Q000473:pathology*
D011768:Pyruvate Dehydrogenase Complex; D007655:Ketoglutarate Dehydrogenase Complex; D014174:Transketolase