Of the pathological conditions associated with alcoholism, the etiology of Wernicke-Korsakoff's syndrome is one of the most well defined. Thiamine deficiency is clearly established as the causal factor. The pentose cycle, which supplies NADPH for the maintenance of cellular integrity and for fatty acid synthesis, is dependent on transketolase, a thiamine-dependent enzyme, for the functioning of this pathway. Despite the importance of the pentose cycle, neither control of flux nor of the level of pentose cycle intermediates is well understood. We have shown that in both starved and ad libitum fed animals the level of pentose cycle metabolites and metabolites of glycolysis are interdependent. The equlibrium relationships defined by the enzymes of the nonoxidative pentose cycle result in considerable stability in the level of pentose cycle intermediates. In dietary situations where the relative amounts of transketolase and transaldolase decrease with respect to glucose 6-P dehydrogenase, these equilibrium relationships are not valid. Under these circumstances, the tissue content of pentose cycle intermediates are elevated more than twenty-fold above those observed in starved animals.
