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Pathway Description
Lac Operon
Escherichia coli
Signaling Pathway
The lac operon in E. coli produces three proteins that are used to metabolize lactose in the absence of glucose. If glucose is present in the cell, cAMP levels will be low, and only a small amount will be able to bind to the cAMP-activated global transcriptional regulator (CRP or CAP). Without cAMP bound, the protein is unactivated, and cannot bind to the activator binding site of the operon. However, when glucose levels are low, cAMP levels are higher, and more can bind to and activate CRP, allowing it to activate the operon. At the same time, if lactose levels in the cell are low, there will be minimal amounts of allolactose produced by any beta-galactosidase present currently in the cell. Allolactose is necessary to bind to the lactose operon repressor, and without allolactose bound to the repressor, it is tightly bound to the operator region of the operon. However, when concentrations of lactose are higher in the cell, more allolactose is produced, and when it binds to the repressor, the repressor cannot bind to the operator, freeing it and allowing RNA polymerase to bind. This, combined with the binding of the CRP protein to the activator binding site leads to all three genes in the operon being transcribed.
The first gene, lacZ, encodes the protein beta-galactosidase, an enzyme that hydrolyzes beta-galactosides into monosaccharides. In this instance, it hydrolyzes lactose into glucose and galactose. In some cases, it can also cause the isomerization of lactose into allolactose.
The second gene, lacY, encodes the protein lactose permease, which is a transport protein that pumps lactose into the cell by using a proton gradient that also flows into the cell.
Finally, the last gene, lacA, encodes the protein galactoside O-acetyltransferase, an enzyme that catalyzes the transfer of the acetyl group of acetyl-CoA to beta-galactosides. This specific protein is not known to be important to the lac operon, but may be important in detoxifying the bacteria by preventing acetylated galactosides from re-entering the cell.
References
Lac Operon References
Marbach A, Bettenbrock K: lac operon induction in Escherichia coli: Systematic comparison of IPTG and TMG induction and influence of the transacetylase LacA. J Biotechnol. 2012 Jan;157(1):82-8. doi: 10.1016/j.jbiotec.2011.10.009. Epub 2011 Nov 3.
Pubmed: 22079752
Hediger MA, Johnson DF, Nierlich DP, Zabin I: DNA sequence of the lactose operon: the lacA gene and the transcriptional termination region. Proc Natl Acad Sci U S A. 1985 Oct;82(19):6414-8. doi: 10.1073/pnas.82.19.6414.
Pubmed: 3901000
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