The effect of thiamine deficiency on the pyruvate decarboxylase system of the central nervous system

Abstract

The activity of pyruvate decarboxylase (2-oxo-acid carboxy-lyase, EC 4.1.1.1) has been compared in homogenates prepared from tissues of normal, pair-fed control and thiamine-deficient rats. Despite severe symptoms of deficiency the enzymic activity remained essentially normal in cerebral cortex, cerebellum and spinal cord and decreased by only 20% in brain stem. In contrast, the ability of heart, liver and kidney homogenates to decarboxylate pyruvate decreased by about 60%. In the normal central nervous system enzymatic activity is about the same in cortex, cerebellum and brain stem, but substantially lower in spinal cord. While transketolase ( D-sedoheptulose-7-phosphate: D-glyceraldehyde-3-phosphate glycolaldehydetransferase, EC 2.2.1.1), another thiamine-dependent enzyme, appears to be most active in myelinated tracts, pyruvate decarboxylase activity is highest in neuronal aggregates. The former enzyme may reflect oligodendroglial and the latter neuronal oxidative metabolism. In rat brain, transketolase is more susceptible to thiamine deprivation than pyruvate decarboxylase. It is therefore postulated that the principal “biochemical lesion” of the athiaminotic state consists of a failure in the transketolase system which may be responsible for initiating the clinical and pathological changes. The abnormality of pyruvate metabolism may play a secondary role.