THE EFFECT OF DEFICIENCY OF THIAMINE ON THE METABOLISM OF [U‐¹⁴C]GLUCOSE AND [U‐¹⁴C]RIBOSE AND THE LEVELS OF AMINO ACIDS IN RAT BRAIN

Abstract

Abstract— The incorporation of 14C into amino acids of the brain was determined at different times after injection of [U‐14C]glucose and [U‐14C]ribose to rats maintained on thiamine‐supplemented and thiamine‐deficient diets for 22 days. The 14C‐content of amino acids in the brain of thiamine‐deficient rats decreased at times 2–10 min after injection of [U‐14C]glucose. but it increased at 2 min and decreased at times 5–10 min after injection of [U‐14C]ribose. The results of labelling of amino acids indicated that the activities in vivo of the thiamine pyrophosphate requiring enzymes, pyruvate oxidase, a‐oxoglutarate dehydrogenase and transketolase were similar in the two groups. It was suggested that the observed decrease in the labelling of amino acids was due to one or more of the following factors: (i) a decrease in the activities of glycolytic enzymes catalysing the conversion of glucose into triose phosphate; (ii) a decrease in the transport of substrate to the active site of the enzymes; or (iii) altered neurohistopathology of the brain. Thiamine deficiency in rats showed a 5% decrease in glutamate (P < 0–05), 46% decrease in threonine (P < 0001) and 16% increase in glycine (P < 0–01) content of the brain.

Uptake and metabolism of fructose by rat neocortical cells in vivo and by isolated nerve terminals in vitro

“…However, expression of Glut5 by Purkinje cells (Funari et al 2005) and oxidative metabolism of [ 14 C]fructose by cultured cerebellar granule cells (Maher et al 1996) and isolated neocortical nerve terminals (this study) point to metabolism of fructose at least by some neuronal populations or cellular compartments. This notion is strengthened by the pattern of amino acid radiolabeling obtained with [ 14 C]fructose, with a specific activity of alanine > glutamate > glutamine, the same pattern as that obtained with [ 14 C]glucose (Gaitonde et al 1974), the main neuronal energy substrate.…”

“…This notion is strengthened by the pattern of amino acid radiolabeling obtained with [ 14 C]fructose, with a specific activity of alanine > glutamate > glutamine, the same pattern as that obtained with [ 14 C]glucose (Gaitonde et al . ), the main neuronal energy substrate.…”

Brain and behavioral pathology in an animal model of Wernicke's encephalopathy and Wernicke–Korsakoff Syndrome

“…This might be due to impaired TCA cycle turnover as reduced de novo synthesis of GABA is seen in the medial thalamus of PTD-treated rats (Navarro et al, 2008). Deficits of C-glucose incorporation into GABA and glutamate have also been observed (Gaitonde et al, 1974, 1975). Thus, the altered balance of GABA and glutamate levels in the brain may be responsible for the seizures observed during the acute stages of TD in rodent models.…”

Decreased turnover of N‐acetylaspartate in the brain of thiamine‐deficient rats

“…Littermates were separated into two groups; one group (the control group) was maintained on a thiamine-supplemented diet and the other group on a thiamine-deficient diet from day 24 after birth. The composition of the diet and other treatments were described previously (GAITONDE et al, 1974). The animals showed overt signs of neurological dysfunction on the 22nd day of maintenance on the special diet.…”

“…A neutral perchloric acid extract was prepared from the brain. Aspartate was isolated from it; the amount and specific radioactivity were determined (GAITONDE et a/., 1974). Fraction (iii) (see GAI-TONDE et a!., 1974) obtained from the solution of metabolites not absorbed on the cation exchange column contained N-acetylaspartate : it was completely hydrolysed with 3 N-HCl at 1 0 0 for 1 h. Thc amount and specific radioactivity of aspartate (from N-acetylaspartate) were determined as before.…”