Thiamin Deficiency and the Pentose Phosphate Cycle in Rats: Intracerebral Mechanisms

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Abstract
Previous studies have shown that transketolase activity is decreased in the brains of thiamin deficient rats. This study assesses the effect of decreased transketolase levels on the activity of the pentose phosphate cycle in murine thiamin deficient cortex and brainstem. Thiamin deficiency was produced in newborn and adult rats by either pyrithiamin administration or by feeding a low-thiamin diet. Newborn rats were killed at 22 days of age, and adults were killed at the onset of moderate to severe neurological signs. Cortices and brainstems from thiamin deficient and control rats were analyzed for activity of the two regulatory enzymes of the pentose phosphate cycle, glucose-6-phosphate dehydrogenase and 6-phoshogluconate dehydrogenase. Flux through the pathway was measured by the differentially labeled glucose technique in the brainstems of deficient and control adult rats. In both the brainstem and cortex of thiamin deficient rats, areas in which transketolase activity was decreased up to 65%, the activities of the two regulatory enzymes, glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, were unaltered. Further, flux through the pentose phosphate cycle was not decreased as compared to pair-fed control rats. These data do not support the hypothesis that in thiamin deficient rats, a decrease in cerebral transketolase activity leads to a diminished pentose phosphate cycle activity.