Biochemistry: The Chemical Reactions of Living Cells, Volume 2 - D. Metzler 1980

Organization of Metabolism: Catabolic Pathways
Oxidation Pathways Linked to the Tricarboxylic Acid Cycle
γ-Aminobutyrate Shunt

In this section, we examine several other catalytic cycles as well as a series of non-cyclic oxidation pathways for one- and two-carbon substrates utilized by microorganisms.

An interesting variant of The Tricarboxylic Acid Cycle operates in Brain tissue (Fig. 9-4). The Condensation of acetyl-CoA and oxaloacetate (step a) yields citrate as usual, which is subsequently converted into a-ketoglutarate. The latter is then transformed into L-glutamate either via direct amination (step b) or Transamination (step c), with y-aminobutyrate serving as the amino group donor. Both glutamate and y-aminobutyrate are present in high concentrations in brain tissue (10 and 0.8 mM, respectively), and both are recognized as important Neurotransmitters. y-Aminobutyrate is of particular interest because it is virtually absent in other mammalian Tissues; substantial evidence indicates that y-aminobutyrate Functions as a major inhibitor of neuronal activity (Chap. 16, Sec. B, 4, g) [25].

Class="center">

y-Aminobutyrate is formed through the decarboxylation of glutamate (step d) and degraded via transamination (step e) to succinic semialdehyde, which is subsequently oxidized to succinate and oxaloacetate. When these two transamination steps are coupled (as illustrated in Fig. 9-4), a complete cycle is established that operates parallel to the tricarboxylic acid cycle. In this pathway, however, a-ketoglutarate is oxidized to succinate via glutamate and y-aminobutyrate. Notably, this process does not require thiamine pyrophosphate, but it does necessitate the reductive amination of a-ketoglutarate to glutamate. This cycle can be regarded as the y-aminobutyrate shunt and is hypothesized to play a significant role in the overall oxidative METABOLISM of brain tissue.

The y-aminobutyrate shunt has also been discovered in green plants. For instance, radish (Raphanus sativus) accumulates large amounts of y-aminobutyrate under anaerobic conditions [26].