Compartmentation of Acetyl-CoA and Acetylcholine Metabolism in Pyrithiamine Encephalopathy

Abstract

Encephalopathy developing in animals and humans due to thiamine deficiency (TD) is thought to be caused by the decrease of activities of thiamine pyrophosphate-dependent enzymes, pyruvate dehydrogenase (PDH) and oxoglutarate dehydrogenase (OGDH). Impairment of pyruvate oxidation in all tissues leads in turn to general energy deficits and lactic acidemia. In cholinergic neurons the decrease in acetyl-CoA synthesis would additionally cause inhibition of acetylcholine (ACh) synthesis, which should be responsible for most mental and neurological symptoms of TD encephalopathy. This simple concept is however contradicted by several data.