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Chronic alcoholics are at risk to develop lactic acidosis and neurologic symptoms, one example of which is the Wernicke-Korsakoff syndrome. This complex of symptoms includes nerve problems like nystagmus (oscillating eyes), ophthalmoplegia (deviated or weak eye), peripheral numbness/tingling and cerebral problems like confusion, delirium, coma, and memory loss in survivors. Explanation of why certain alcoholics get Wernicke-Korsakoff encephalopathy was suggested when altered transketolase (an important enzyme in the pentose phosphate pathway) was found in these individuals. What is most likely to be important in the development of lactic acidosis and/or Wernicke-Korsakoff susceptibility in alcoholics?
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A deficiency in thiamine resulting from chronic alcohol consumption is one factor underlying alcohol“induced brain damage.
Thiamine is a cofactor , required by three enzymes ( Transketolase, pyruvate dehydrogenase, alpha ketoglutarate) involved in pathways of carbohydrate metabolism ( TCA cycle and gluconeogenesis, HMP shunt) .
Because intermediate products of these pathways are needed for the generation of other essential molecules in the cells (e.g., building blocks of proteins and DNA as well as brain chemicals), a reduction in thiamine can interfere with numerous cellular functions, leading to serious brain disorders, including Wernicke“Korsakoff syndrome, which is found predominantly in alcoholics.
Chronic alcohol consumption can result in thiamine deficiency by causing inadequate nutritional thiamine intake, decreased absorption of thiamine from the gastrointestinal tract, and impaired thiamine utilization in the cells.
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on the other hand:
chronic alcoholics .....> inc.NADPH/NAD......> high NADPH favors the formation of:
Lactate from pyrovate , malate from OAA and Gyceraol-3p from DHAP.....> to divert important gluconeogenetic substrates from entering the pathway......> dec. gluconeogenesis and inc. lactic acidosis.
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sorry ..........>Inc.NADPH/NADP not inc.NADPH/NAD
eople differ in their susceptibility to thiamine deficiency, however, and different brain regions also may be more or less sensitive to this condition.
