What role does thiamine have in the pathophysiology of Wernicke-Korsakoff Syndrome (WKS)?

Updated: May 16, 2018
  • Author: Glen L Xiong, MD; Chief Editor: David Bienenfeld, MD  more...
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Answer

Thiamine is absorbed from the duodenum. The body has approximately 18 days of thiamine stores. Thiamine is converted to its active form, thiamine pyrophosphate, in neuronal and glial cells. Thiamine pyrophosphate serves as a cofactor for several enzymes, including transketolase, pyruvate dehydrogenase, and alpha ketoglutarate, that function in glucose use. The main function of these enzymes in the brain is lipid (myelin sheath) and carbohydrate metabolism, production of amino acids, and production of glucose-derived neurotransmitters.

Thiamine appears to have a role in axonal conduction, particularly in acetylcholinergic and serotoninergic neurons. A reduction in the function of these enzymes leads to diffuse impairment in the metabolism of glucose in key regions of the brain, resulting in impaired cellular energy metabolism.

Within 2-3 weeks of decreased intake and thiamine depletion, areas of the brain with the highest thiamine content and turnover demonstrate cellular impairment and injury. The earliest biochemical change is the decrease in α-ketoglutarate-dehydrogenase activity in astrocytes. Acute thiamine deficiency leads to mitochondrial dysfunction and therefore oxidative toxicity in areas of the brain starting with areas with the highest metabolic activity. The exact mechanism of neuronal cell death remains to be elucidated. [25]


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