Premium
Astrocyte Leucine Metabolism: Significance of Branched‐Chain Amino Acid Transamination
Author(s) -
Yudkoff Marc,
Daikhin Yevgeny,
Grunstein Lev,
Nissim Ilana,
Stern Janet,
Pleasure David,
Nissim Itzhak
Publication year - 1996
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1996.66010378.x
Subject(s) - leucine , transamination , glutamine , biochemistry , amino acid , glutamate receptor , aminooxyacetic acid , metabolism , extracellular , biology , astrocyte , glutamic acid , chemistry , endocrinology , enzyme , central nervous system , receptor
Abstract: We studied astrocytic metabolism of leucine, which in brain is a major donor of nitrogen for the synthesis of glutamate and glutamine. The uptake of leucine into glia was rapid, with a V max of 53.6 ± 3.2 nmol/mg of protein/min and a K m of 449.2 ± 94.9 µ M . Virtually all leucine transport was found to be Na + independent. Astrocytic accumulation of leucine was much greater (3×) in the presence of α‐aminooxyacetic acid (5 m M ), an inhibitor of transamination reactions, suggesting that the glia rapidly transaminate leucine to α‐ketoisocaproic acid (KIC), which they then release into the extracellular fluid. This inference was confirmed by the direct measurement of KIC release to the medium when astrocytes were incubated with leucine. Approximately 70% of the leucine that the glia cleared from the medium was released as the keto acid. The apparent K m for leucine conversion to extracellular KIC was a medium [leucine] of 58 µ M with a V max of ∼2.0 nmol/mg of protein/min. The transamination of leucine is bidirectional (leucine + α‐ketoglutarate ? KIC + glutamate) in astrocytes, but flux from leucine → glutamate is more active than that from glutamate → leucine. These data underscore the significance of leucine handling to overall brain nitrogen metabolism. The release of KIC from glia to the extracellular fluid may afford a mechanism for the “buffering” of glutamate in neurons, which would consume this neurotransmitter in the course of reaminating KIC to leucine.