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Thiamine-dependent enzyme changes in the brains of alcoholics: relationship to the Wernicke-Korsakoff syndrome.

Abstract
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.
AuthorsR F Butterworth, J J Kril, C G Harper
JournalAlcoholism, clinical and experimental research (Alcohol Clin Exp Res) Vol. 17 Issue 5 Pg. 1084-8 (Oct 1993) ISSN: 0145-6008 [Print] England
PMID8279670 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Pyruvate Dehydrogenase Complex
  • Ketoglutarate Dehydrogenase Complex
  • Transketolase
Topics
  • Adult
  • Aged
  • Alcohol Amnestic Disorder (enzymology, pathology)
  • Alcoholism (enzymology, pathology)
  • Alzheimer Disease (enzymology, pathology)
  • Brain (enzymology, pathology)
  • Cerebellum (pathology)
  • Female
  • Hepatic Encephalopathy (enzymology, pathology)
  • Humans
  • Ketoglutarate Dehydrogenase Complex (metabolism)
  • Liver Cirrhosis, Alcoholic (enzymology, pathology)
  • Male
  • Middle Aged
  • Pyruvate Dehydrogenase Complex (metabolism)
  • Thiamine Deficiency (enzymology, pathology)
  • Transketolase (metabolism)
  • Wernicke Encephalopathy (enzymology, pathology)

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