DECREASED METABOLISM <i>IN VIVO</i> OF GLUCOSE INTO AMINO ACIDS OF THE BRAIN OF THIAMINE‐DEFICIENT RATS AFTER TREATMENT WITH PYRITHIAMINE

Abstract

Abstract— Thiamine deficiency produced by administration of pyrithiamine to rats maintained on a thiamine‐deficient diet resulted in a marked disturbance in amino acid and glucose levels of the brain. In the two pyrithiamine‐treated groups of rats (Expt. A and Expt. B) there was a significant decrease in the levels of glutamate (23%, 9%) and aspartate (42%, 57%), and an increase in the levels of glycine (26%, 27%) in the brain, irrespective of whether the animals showed signs of paralysis (Expt. A) or not (Expt. B). as a result of thiamine deficiency. A significant decrease in the levels of γ‐aminobutyrate (22%) and serine (28%) in the brain was also observed in those pyrithiamine‐treated rats which showed signs of paralysis (Expt. A). Threonine content increased by 57% in Expt. A and 40% in Expt. B in the brain of pyrithiamine‐treated rats, but these changes were not statistically significant. The utilization of [U‐ 14 C]glucose into amino acids decreased and accumulation of glucose and [U‐ 14 C]glucose increased significantly in the brain after injection of [U‐ 14 C]glucose to pyrithiamine‐treated rats which showed abnormal neurological symptoms (Expt. A). The decrease in 14 C‐content of amino acids was due to decreased conversion of [U‐ 14 C]glucose into alanine, glutamate, glutamine, aspartate and γ‐aminobutyrate. The flux of [ 14 C]glutamate into glutamine and γ‐aminobutyrate also decreased significantly only in the brain of animals paralysed on treatment with pyrithiamine. The decrease in the labelling of, amino acids was attributed to a decrease in the activities of pyruvate dehydrogenase and α‐oxoglutarate dehydrogenase in the brain of pyrithiamine‐treated rats. The measurement of specific radioactivity of glucose, glucose‐6‐phosphate and lactate also indicated a decrease in the activities of glycolytic enzymes in the brain of pyrithiamine‐treated animals in Expt. A only. It was suggested that an alteration in the rate of oxidation in vivo of pyruvate in the brain of thiamine‐deficient rats is controlled by the glycolytic enzymes, probably at the hexokinase level. The lack of neurotoxic effect and absence of significant decrease in the metabolism of [U‐ 14 C]glucose in the brain of pyrithiamine‐treated animals in Expt. B were probably due to the fact that animals in Expt. B were older and weighed more than those in Expt. A, both at the start and the termination of the experiments.