The GABA operon is responsible for the conversion of γ-aminobutyrate ( GABA ) to succinate . The GABA operon includes three structural genes — gabD , gabT, and gabP , which encode semialdehyde dehydrogenase succinate, GABA transaminase, and GABA permease, respectively. There is a regulating csiR gene , below the operon, which encodes the putative transcriptional repressor [1] and is activated when nitrogen is restricted.
The GABA operon was detected in Escherichia coli and significant homologs for enzymes were found in organisms such as Saccharomyces cerevisiae , rats and humans [2] .
Nitrogen restriction is a condition for the activation of GABA genes. The enzymes produced by these genes convert GABA to succinate, which then enters the TCA circuit to be used as an energy source. The GABA operon is also known for promoting polyamine homeostasis during growth while limiting nitrogen and maintaining high concentrations of internal glutamate under stress. [3]
Content
Structure
The GABA operon consists of three structural genes:
- gabT : encodes GABA transaminase, which produces amber semi-aldehyde .
- gabD : encodes NADP-dependent succinic semi-aldehyde dehydrogenase, which oxidizes succinic semi-aldehyde to succinate.
- gabP : encodes a DNA-specific permease.
The physiological significance of the operon
The GabT gene encodes GABA transaminase, an enzyme that catalyzes the conversion of GABA and 2-oxoglutarate into semialdehyde succinate and glutamate. Semi-aldehyde succinate is then oxidized to succinate with the help of semialdehyde dehydrogenase succinate (which is encoded by the gabP gene ), thereby entering into the TCA chain as a useful energy source. The GABA operon promotes homeostasis of polyamines, such as putrescine during growth with limited nitrogen. It is also known about its role in maintaining high concentrations of internal glutamate under stress.
Regulation
Differential Promoter Regulation
Gene expression in the operon is controlled by three differentially regulated promoters , [4] two of which are controlled by RpoS , encoding the sigma-factor σ S.
- csiD p : - σ S -dependent and is activated exclusively by carbon starvation, because the action of cAMP-CRP significantly activates the σ S containing RNA polymerase in the csiD promoter.
- gabD p1 : - σ 70 is dependent and is induced by numerous stresses.
- gabD p2 : - σ 70 dependent and controlled by Nac (governing the assimilation of nitrogen) regulatory proteins expressed in accordance with the restriction of nitrogen.
Regulatory Mechanism
Activation
The csiD promoter ( csiD p ) is important for the expression of csiD (genes induced by carbon starvation), ygaF and GABA genes. CsiD p is activated only in conditions of carbon starvation and the stationary phase, during which cAMP accumulates in high concentrations in the cell. Binding of cAMP to the cAMP receptor protein (CRP) forces CRP to bind tightly to a specific DNA site in the 'csiD p promoter , thereby activating gene transcription downstream of the promoter.
gabD p1 provides additional gabDTP management in the region. gabD p1 activates σ S causing conditions such as hyperosmotic and acidic shifts, in addition to starvation and the stationary phase. The gabD p2 promoter, on the other hand, is σ 70 -dependent and is activated when nitrogen is limited. Under conditions of nitrogen restriction, the nitrogen regulator Nac binds to a site located just above the promoter expressing the GABA genes. When activated, GABA genes produce enzymes that convert GABA to succinate.
Repression
The presence of nitrogen activates the csiR gene , located below the gabP gene. The csiR gene encodes a protein that acts as a transcriptional repressor for the csiD-ygaF-GABA operons, therefore, disabling the degradation of the GABA pathway.
Eukaryotic Analogs
The degradation of GABA pathways exists in almost all eukaryotic organisms and occurs under the action of similar enzymes. Although GABA in E. coli is mainly used as an alternative source of energy, GABA in higher eukaryotic organisms acts as an inhibitory neurotransmitter , as well as a regulator of muscle tone. Ways of degradation of GABA in eukaryotes are responsible for the inactivation of GABA.
Notes
- ↑ Schneider, Barbara L .; Ruback, Stephen; Kiupakis, Alexandros K .; Kasbarian, Hillary; Pybus, Christine; Reitzer, Larry. The Escherichia coli gabDTPC Operon: Specific γ-Aminobutyrate Catabolism and Nonspecific Induction (Eng.) // Journal of Bacteriology : journal. - 2002. - Vol. 184 , no. 24 - p . 6976-6986 . - DOI : 10.1128 / JB.184.24.6976-6986.2002 . - PMID 12446648 .
- ↑ Bartsch, Klaus; Von Johnn-Marteville, Astrid; Schulz, Arno. Molecular Analysis of the Escherichia coli genus Cluster: Sequence of the Glutamate; : journal. - 1990. - Vol. 172 , no. 12 - P. 7035-7042 . - PMID 2254272 .
- ↑ Metzner, Martin; Germer, Jens; Hengge, Regine. Multiple stress signal integration σS-dependent csiD-ygaF-gabDTP operon in Escherichia coli (English) // Molecular Microbiology: journal. - 2003. - Vol. 51 , no. 3 - P. 799-811 . - DOI : 10.1046 / j.1365-2958.2003.03867.x . - PMID 14731280 .
- ↑ Joloba, Moses L .; Clemmer, Katy M .; Sledjeski, Darren D .; Rather, Philip N. Activation of the Lipopolysaccharide in Escherichia coli (Eng.) // Journal of Bacteriology : journal. - 2004. - Vol. 186 , no. 24 - p . 8542–8546 . - DOI : 10.1128 / JB.186.24.8542-8546.2004 . - PMID 15576807 .