Effects of Changes in Brain Metabolism on Levels of Pentose Phosphate Pathway Intermediates

Abstract

Several metabolites of the pentose phosphate pathway, together with related intermediates of the Embden-Meyerhof pathway, were measured in cerebral tissue of mice after periods of ischemia, anesthesia by phenobarbital, hyperthermia, hypothermia, and iodoacetate and fluoroacetate poisoning. Normal levels (micromoles per kg) were found to be 6-P-gluconate, 10; ribulose-5-P, 7; xylulose-5-P, 14; and erythrose-4-P, less than 2. The sum of ribose-5-P and sedoheptulose-7-P was 64 µmoles per kg. During 5 min of complete ischemia, 6-P-gluconate decreased 30% and xylulose-5-P fell 80%. Ribulose-5-P was also sharply reduced. Anesthesia resulted in increases of 40 to 50% for ribulose-5-P and xylulose-5-P without change in 6-P-gluconate. Anesthesia also prevented or greatly diminished the changes in phosphate intermediates induced by ischemia. Hypothermia resulted in decreases in ribulose-5-P and xylulose-5-P, and an increase in 6-P-gluconate. Conversely, hyperthermia exactly reversed the pattern of these changes. Iodoacetate intoxication resulted in marked increases in ribulose-5-P and xylulose-5-P, but glucose-6-P and 6-P-gluconate fell below control values. There did not appear to be any direct correlation between the magnitude of the pentose phosphate increases and those of the triose phosphates. In fluoroacetate-treated mice glucose-6-P levels increased approximately 3-fold, whereas intermediates in the pentose phosphate pathway and triose phosphates remained near control levels or fell slightly. The results are compatible with a regulatory mechanism at both of the dehydrogenase steps with some effect of glyceraldehyde-P and fructose-6-P concentrations on the levels of intermediates of the pentose pathway below 6-P-gluconate.