title: Specific replacements of pyruvate for trophic support of central and peripheral nervous system neurons.
abstract: When embryonic central nervous system neurons are seeded at low densities with Eagle's basal medium supplemented with the serum substitute N1, glucose, and glutamine, neuronal survival for even 24 h requires the additional supply of exogenous pyruvate--and so does the survival of many peripheral nervous system neurons. Pyruvate can be replaced by alpha-ketoglutarate or oxaloacetate, but not by Krebs cycle substrates that are not keto acids. Most other alpha-keto acids tested (though not beta- or gamma-keto acids) also mimic pyruvate. The apparent equivalence to pyruvate of all these compounds includes identical ED50 values (300 microM for embryonic avian fore-brain neurons, 30-40 microM for rat hippocampal neurons), and also identical susceptibilities to the pyruvate-sparing effects of other low-molecular-weight agents present in Dulbecco's modified Eagle's medium or in astroglia conditioned medium. The substitute alpha-keto acids, however--unlike pyruvate, alpha-ketoglutarate, or oxaloacetate--support cell survival only in the presence of alpha-amino acids that transaminate to alpha-ketoglutarate, oxaloacetate, or pyruvate. The alpha-keto acids, therefore, operate as acceptors of amino groups from appropriate donors to generate Krebs cycle-relevant substrates. Consistent with this view, [14C]glutamate did not generate appreciable 14CO2 unless accompanied by a suitable alpha-keto acid.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D001921:Brain / Q000166:cytology* / Q000378:metabolism; D002478:Cells, Cultured; D002642:Chick Embryo; D002952:Citric Acid Cycle; D003470:Culture Media; D006801:Humans; D007651:Keto Acids / Q000378:metabolism; D007656:Ketoglutaric Acids / Q000378:metabolism; D008168:Lung / Q000166:cytology; D009474:Neurons / Q000254:growth & development* / Q000378:metabolism; D010071:Oxaloacetates / Q000378:metabolism; D010525:Peripheral Nerves / Q000166:cytology* / Q000378:metabolism; D011773:Pyruvates / Q000378:metabolism*; D019289:Pyruvic Acid; D051381:Rats
chemical_list: D003470:Culture Media; D007651:Keto Acids; D007656:Ketoglutaric Acids; D010071:Oxaloacetates; D011773:Pyruvates; D019289:Pyruvic Acid