Control of cerebral metabolite levels: I. Amino acid uptake and levels in various species

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This study confirmed previous work which indicated that steady-state uptake levels of amino acids in brain slices are primarily regulated by influx and efflux. To determine whether such fluxes also have a controlling role in living brain, levels of brain amino acids from various animals were compared with the uptake of the same amino acids by brain slices. For these studies, brains of newborn and adult mouse and adult rat, guinea pig, hen, and frog were used. In the composition of the cerebral amino acid pool, differences were found between newborn and adult mice, with adult brain containing lower levels of most amino acids except glutamic acid and its related compounds. There was great similarity in the composition of the free amino acid pool of the brain in all species, glutamic acid being the highest in all brains, followed by taurine; compounds at high level were high in all species, and those at low level were low in all the brains examined. There was also similarity between the various species in the uptake of amino acid by brain slices. In each species the order of uptake was phenylalanine < leucine < lysine < taurine < glycine < glutamate. Brain slice uptake and physiological brain levels showed parallelism in that amino acids at high levels in the living brain were usually taken up by slices to a higher degree than amino acids at low levels in the brain. In a comparison of newborn and adult mice, and in a comparison of adults of the various species, physiological brain concentrations and uptake by slices were not parallel in all cases, and it was concluded that although factors that can be measured in slices play an important role, the level of amino acids in the living brain is determined by other mechanisms as well as by those that determined the steady-state uptake levels of amino acids in brain slices.