The gab operon is responsible for the conversion of γ-aminobutyrate to succinate. The gab operon comprises three structural genes – gabD, gabT and gabP – that encode for a succinate dehydrogenase, GABA transaminase. There is a regulatory gene csiR, downstream of the operon, the gab operon has been characterized in Escherichia coli and significant homologies for the enzymes have been found in organisms such as Saccharomyces cerevisiae, rats and humans. Limited nitrogen conditions activate the gab genes, the enzymes produced by these genes convert GABA to succinate, which then enters the TCA cycle, to be used as a source of energy. The gab operon is also known to contribute to polyamine homeostasis during nitrogen-limited growth, the gab operon consists of three structural genes, gabT, encodes a GABA transaminase that produces succinic semialdehyde. GabD, encodes an NADP-dependent succinic semialdehyde dehydrogenase, which oxidizes succinic semialdehyde to succinate, the gabT gene encodes for GABA transaminase, an enzyme that catalyzes the conversion of GABA and 2-oxoglutarate into succinate semialdehyde and glutamate. Succinate semialdehyde is oxidized into succinate by succinate semialdehyde dehydrogenase which is encoded by the gabP gene. The gab operon contributes to homeostasis of polyamines such as putrescine and it is also known to maintain high internal glutamate concentrations under stress conditions. GabDp1, is σS -dependent and is induced by multiple stresses, gabDp2, is σ70 dependent and is controlled by Nac regulatory proteins expressed under nitrogen limitation. The csiD promoter is essential for the expression of csiD, ygaF, the csiDp is activated exclusively under carbon starvation conditions and stationary phase during which cAMP accumulates in high concentrations in the cell. The binding of cAMP to the receptor protein causes CRP to bind tightly to a specific DNA site in the csiDp promoter. The gabDp1 exerts a control over the gabDTP region. The gabDp1 is activated by σS inducing conditions such as hyperosmotic and acidic shifts besides starvation, the gabDp2 promoter on the other hand, is σ70 dependent and is activated under nitrogen limitation. In nitrogen limiting conditions, the nitrogen regulator Nac binds to a site located just upstream of the promoter expressing the gab genes, the gab genes upon activation produce enzymes that degrade GABA to succinate. The presence of nitrogen activates the csiR gene located downstream of the gabP gene, the csiR gene encodes a protein that acts as a transcriptional repressor for csiD-ygaF-gab operon hence shutting off the GABA degradation pathway. GABA degradation pathways exists in almost all organisms and takes place by the action of similar enzymes. Although, GABA in E. GABA degradation pathways in eukaryotes are responsible for the inactivation of GABA
GABA degradation mechanism
Structure and regulatory mechanism of the gab operon.