Biochemical Aspects of the Pathogenesis of the Wernicke‐Korsakoff Syndrome

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Abstract
The Michaelis‐Menten constant of human erythrocyte transketolase for thiamin diphosphate (TDP) was found to be 2.3 ± 1.2 μM, 2.3 ± 1.3 μM and 2.0 ± 1.0 μM in respective samples from 54 healthy controls, 6 alcoholic controls and 53 patients suffering the Wernicke‐Korsakoff syndrome, when determined by simultaneous addition of TDP and substrates to apoenzyme. When apoenzyme and various TDP concentrations were preincubated 1 h before addition of substrates, the respective K TDP/m values were 54 ± 18 nM, 65 ± 18 nM and 67 ± 26 nM. Thus carefully standardized measurements of K TDP/m fail to detect a variant of transketolase associated with the Wernicke‐Korsakoff syndrome, suggesting that other documentation of variants is dependent upon a particular set of conditions which have yet to be identified and reproduced. Acetaldehyde at 50 mM for 15 min inactivated apotransketolase much more than holotransketolase but had no effect upon the K TDP/m. Thus acetaldehyde, generated by metabolism of ethanol, could exacerbate the metabolic consequences of thiamin deficiency and obscure the assessment of thiamin nutrition by measurement of the erythrocyte transketolase “TDP effect”.