Transamination of glutamate to tricarboxylic acid-cycle intermediates in cultured neurons correlates with the ability of oxo acids to support neuronal survival in vitro.
Cultures of central-nervous-system neurons at low densities require for their survival exogenous pyruvate, alpha-oxoglutarate or oxaloacetate, even in the presence of high glucose concentrations. Most other alpha-oxo acids support cell survival only in the presence of alpha-amino acids which transaminate to alpha-oxoglutarate, oxaloacetate or pyruvate. The alpha-oxo acids therefore operate as acceptors of amino groups from appropriate donors to generate tricarboxylic acid-cycle-relevant substrates, and these alpha-oxo acids provide for neuronal support only insofar as they make it possible for exogenously supplied alpha-amino acid precursors to generate intracellularly one of the three critical metabolites. To examine more closely the relationship between transamination activity and neuronal survival, we measured 14CO2 production from [14C]glutamate in the presence of appropriate alpha-oxo acid partners by using 8-day-embryonic chick forebrain, dorsal-root-ganglion and ciliary-ganglion neurons. Neuronal survival was measured concurrently in monolayer neuronal cultures maintained with the corresponding amino acid/oxo acid pairs. Forebrain and ganglionic cell suspensions both produced 14CO2 from [14C]glutamate, which accurately correlated with 24 h neuronal survival. Concentrations of glutamate or alpha-oxo acid which provide for maximal neuronal survival also produced maximal amounts of 14CO2. The same ability to generate CO2 from glutamate (in the presence of the appropriate alpha-oxo acids) can ensure neuronal survival in 24 h cultures and therefore must meet energy or other metabolic needs of those neurons which glucose itself is unable to satisfy.
Facci
L
L
Skaper
S D
SD
Varon
S
S
D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D002470:Cell Survival; D002478:Cells, Cultured; D002642:Chick Embryo; D002952:Citric Acid Cycle; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid; D007651:Keto Acids / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*
D005971:Glutamates; D007651:Keto Acids; D002245:Carbon Dioxide; D018698:Glutamic Acid