GABA and GHB Neurotransmitters in Plants and Animals - Communication in Plants: Neuronal Aspects of Plant Life - page 179

12.3.3
The GABA Shunt and Redox Imbalance: from Bacteria to Humans
As indicated earlier, some of the effects of GHB in mammals suggest its
involvement in maintaining the redox state of cells. Studies in microor-
ganisms (Poole and Allaway 2000) also suggested the GABA shunt as part
of a metabolic network that helps maintain redox equilibrium. In anoxic
environments bacteria of the orders Clostridiales ( Firmicutes ,phylum Bac-
teria XIII) and Fusobacteriales ( Fusobacteria ,phylum Bacteria XXI; Garrity
2001) ferment amino acids in the anaerobic food chain, by which proteins
and other polymers are degraded to methane and CO 2 . Bacterial anaerobic
catabolism of glutamate to fatty acids involves the decarboxylation of glu-
tamate to GABA and its conversion via GHB to acetate and butyrate (Buckel
2001). In legume nodules glutamate appears in large quantities (Miller et al.
1991; Vance and Heichel 1991; Salminen and Streeter 1992). It was shown
that this amino acid accumulates partly following the inhibition of the bac-
terial enzyme 2-oxoglutarate dehydrogenase (2OGDH) during symbiosis
(Walshaw et al. 1997), when high NADH levels are found in bacteroids, ow-
ing to oxygen limitation. Thus, the removal of intermediates, reductants,
or ATP from the bacteroids is imperative for TCA cycle efficiency (Lodwig
and Poole 2003). Under hypoxic conditions the GABA shunt may bypass
the 2OGDH block and feed the TCA cycle with succinate or remove two
NADH molecules from the system by producing GHB (Fig. 12.1; Miller et
al. 1991; Prell et al. 2002). In turn, GHB may be used as a precursor for the
synthesis of the carbon-sink polymer polyhydroxybutyrate (PHB). PHB
also accumulates during the stationary phase of growth of bacteroids when
cells become limited for an essential nutrient but have excess carbon source
(Udvardi and Day 1997; Poole and Allaway 2000).
In mammal nerve cells, the metabolic processes under hypoxic condi-
tions are still under debate. Tretter and Adam-Vizi (2000) tested the relation
between ROI level and enzymes of the TCA cycle in nerve terminals. Their
study revealed that, similarly to bacteroids, 2-OGDH is a rate-limiting en-
zymes of the TCA cycle, and as such it may have a flux-controlling function
(Tretter and Adam-Vizi 2000, and reference therein). Inhibition of 2OGDH
plays a critical role in limiting the amount of reducing power in the form
of NADH during H 2 O 2 -induced oxidative stress (Chinopoulos et al. 1999;
Tretter and Adam-Vizi 2000). H 2 O 2 modulates 2-OGDH activity possibly
by modifying sulfhydryl group(s) on 2OGDH (Nulton-Persson et al. 2003).
The GABA shunt may function as a route to overcome the 2OGDH block
and further provide the system with NADH during the NAD + -dependent
SSADH-driven reaction.
TheseandotherpiecesofevidencesuggesttheGABAshuntmaybe
of significance in maintaining redox equilibrium. A deficient shunt and