Glutamic acid, other amino acids and related compounds as substrates for cerebral tissues: their effects on tissue phosphates

Abstract

Slices of mammalian cerebral cortex resynthesized phosphocreatine on incubation in media containing (5-25 mM) glucose, lactic acid, pyruvic acid, malic acid or oxaloacetic acid. A lesser resynthesis occurred with [alpha]-oxoglutarate, and little or none with glutamic acid, aspartic acid and gamma-aminobutyric acid as the only oxidizable substrates. The concentrations of phosphocreatine produced in the tissue in the presence of glucose were diminished by the further addition of 5-25 mM-D- or L-glutamic acid, L-aspartic acid or gamma-aminobutyric acid, asparagine, alanine or [beta]-alanine, but were slightly increased by the further addition of 25 mM-L-methionine or L-phenylalanine. Respiratory rates were increased, in the presence of glucose, by [alpha]-oxoglutarate and oxaloacetate but were diminished by the further addition of L-phenylalanine or L-tryptophan. The depression of phosphocreatine by L-glutamate was not prevented by the addition of creatine to the medium. Also creatine assimilation was not affected by L-glutamate, L-aspartate or [beta]-alanine. Tissue inorganic pyrophosphate, normally at 0.2 [mu]mole/g., was diminished by addition of L-glutamate. Creatine-phosphokinase activity in cerebral homogenates was unaffected by the addition of glutamate or several nucleotide phosphates, when observed with phosphocreatine and adeno-sine diphosphate as initial reactants. Phosphocreatine synthesis by cerebral homogenates was also unaffected by the addition of L-glutamate. The rate of phosphocreatine breakdown in cerebral slices on the addition of 20 mM-L-glutamate was about 20 [mu]moles/g./hr. and was not lowered by the addition of 20 [mu]M-cocaine. Simultaneous addition of 5 mM-NH4+ ion and L-glutamate more than doubled this rate. The rates of increase of tissue glutamine and loss of ammonia on addition of 20 mM-glutamate were similar to those for the loss of phosphocreatine and increase in inorganic phosphate, indicating that these changes were due to glutamine synthesis.