GABA and glutamate in the human brain

Neuroscientist. 2002 Dec;8(6):562-73. doi: 10.1177/1073858402238515.


Cortical excitability reflects a balance between excitation and inhibition. Glutamate is the main excitatory and GABA the main inhibitory neurotransmitter in the mammalian cortex. Changes in glutamate and GABA metabolism may play important roles in the control of cortical excitability. Glutamate is the metabolic precursor of GABA, which can be recycled through the tricarboxylic acid cycle to synthesize glutamate. GABA synthesis is unique among neurotransmitters, having two separate isoforms of the rate-controlling enzyme, glutamic acid decarboxylase. The need for two separate genes on two chromosomes to control GABA synthesis is unexplained. Two metabolites of GABA are present in uniquely high concentrations in the human brain. Homocarnosine and pyrrolidinone have a major impact on GABA metabolism in the human brain. Both of these GABA metabolites have anticonvulsant properties and can have a major impact on cortical excitability.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Brain / drug effects
  • Brain / metabolism*
  • Glutamic Acid / analysis
  • Glutamic Acid / drug effects
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism*
  • Humans
  • gamma-Aminobutyric Acid / analysis
  • gamma-Aminobutyric Acid / drug effects
  • gamma-Aminobutyric Acid / genetics
  • gamma-Aminobutyric Acid / metabolism*


  • Anticonvulsants
  • Glutamic Acid
  • gamma-Aminobutyric Acid