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.
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Authors | R F Butterworth, J J Kril, C G Harper |
Journal | Alcoholism, clinical and experimental research
(Alcohol Clin Exp Res)
Vol. 17
Issue 5
Pg. 1084-8
(Oct 1993)
ISSN: 0145-6008 [Print] England |
PMID | 8279670
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Pyruvate Dehydrogenase Complex
- Ketoglutarate Dehydrogenase Complex
- Transketolase
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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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