Reduced activities of thiamine-dependent enzymes in brains of alcoholics in the absence of Wernicke's encephalopathy.
The relative roles of alcohol per se, thiamine deficiency, and liver disease in the pathogenesis of alcohol-related brain damage have not been fully elucidated. In particular, the extent to which alterations of brain thiamine metabolism contribute to cognitive dysfunction in alcoholism in the absence of Wernicke's encephalopathy has not been established. In the present study, thiamine diphosphate-dependent enzymes were measured using standard spectrophotometric techniques in homogenates of brain tissue obtained at autopsy from eight alcoholic patients, all of whom died in hepatic coma without clinical or neuropathological evidence of Wernicke's encephalopathy and six nonalcoholic, age-matched controls, matched for autopsy delay time and free, at the time of death, from gross malnutrition or other neurological or psychiatric disorders. Transketolase activities were reduced in cerebellum (by 35%, p < 0.01), thalamus (by 35%, p < 0.01), frontal cortex (by 22%, p < 0.01), temporal cortex (by 20%, p < 0.01), and prefrontal cortex (by 19%, p < 0.01). Activities of the pyruvate dehydrogenase complex were selectively reduced in prefrontal cortex by 25% (p < 0.01). Activities of alpha-ketoglutarate dehydrogenase were within normal limits in all brain regions of alcoholic patients. The generalized reductions of transketolase activity undoubtedly result from thiamine deficiency. Previous studies suggest that the presence of liver disease may exacerbate thiamine deficiency in alcoholics. A sustained loss of transketolase activity in brain could result in disruption of pentose shunt activity and concomitant reductions in reducing equivalents and lipid metabolism within the cell. The selective loss of pyruvate dehydrogenase activity in prefrontal cortex of alcoholic cirrhotics could relate to the phenomenon of hepatic coma.(ABSTRACT TRUNCATED AT 250 WORDS)
D000368:Aged; D000437:Alcoholism / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D005260:Female; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism*; D012016:Reference Values; D013831:Thiamine / Q000378:metabolism*; D014174:Transketolase / Q000378:metabolism*; D014899:Wernicke Encephalopathy / Q000473:pathology
D011768:Pyruvate Dehydrogenase Complex; D007655:Ketoglutarate Dehydrogenase Complex; D014174:Transketolase; D013831:Thiamine