Factors influencing the anaerobic glycolysis of brain and tumour

Abstract

The effects of calcium ions, a variety of organic bases and sodium pyruvate on the anaerobic glycolysis of guinea-pig brain and tumour slices have been investigated. The presence of calcium ions exercises a marked stimulation of the conversion of glucose into lactic acid in presence of guinea-pig brain slices when these are bathed in a calcium-free medium at pH 7·5. This inhibitory effect on glycolytic rate resulting from the absence of calcium is largely overcome by decreasing the pH to 7·0. The optimal stimulating concentration of calcium is 0·004 m. The presence of 0·001 m-sodium pyruvate accelerates anaerobic brain glycolysis very markedly in a calcium-free medium, but only slightly in the presence of an optimal calcium concentration. A number of organic bases (pyrrole, quinoline,p-chloraniline, benzidine,α-naphthylamine, 2:4-lutidene, pyridine, aniline, triethylamine, choline,N-methylpyridine, urea, nicotinamide) accelerate anaerobic brain glycolysis in a calcium-free medium, the concentrations needed for optimal activity varying considerably, e. g. pyrrole, 32 mM; quinoline, 1·6 mM ; urea, 64 mM; nicotinamide, 200 mM. The efficiency of the organic bases in replacing calcium for anaerobic brain glycolysis can be, in general, correlated with their dissociation constants. The effects of the organic bases cannot be explained in terms ofDPN-ase inhibitions. Anaerobic glycolysis of tumour slices exhibits little or no calcium dependence and is not affected by the organic bases effective with brain. No additive effects are obtained by combinations of calcium ions, organic bases and sodium pyruvate used at their optimal stimulating concentrations. The results point to a common site of action of all the stimulating substances, or to a common effect on a rate-limiting step in brain anaerobic glycolysis. There seems to be no correlation between the abilities of the organic bases to stimulate glycolysis and their abilities to inhibitDPN-ase. The results of physiological tests show that the organic bases pyrrole, quinoline andp-chloraniline exert neurological effects simulating that of calcium ions in abolishing the spontaneous firing of cat cervical sympathetic ganglia. Unlike calcium ions, however, there was no restoration of sympathetic transmission. The bases act in physiological systems at the same concentrations and with about the same relative potency as in anaerobic glycolysis. It seems that the bases (as well as calcium) establish new membrane equilibria reflected on the one hand by marked neurophysiological activities and on the other by changed glycolytic rates. The suggestion is made that the neurone surface is an important site of glucose metabolism and that theDPN-DPNHratio there plays a significant rate-limiting role.