Catabolic Repression
The presence of glucose is known to prevent the induction of the lac operon, this phenomenon is known as catabolic repression (glucose effects). It assures that glucose is metabolized when present, in preference to other, less efficient, energy sources.
The catabolic repression of the lac operon and several other operons is mediated by a regulatory protein called CAP (for catabolic activator protein) and a small effector molecule called cyclic AMP (adenosine-3’,5’-monophosphate).
Because CAP binds cAMP when this mononucleotide is present at sufficient concentrations, it is sometimes called cyclic AMP receptor protein.
- RNA polymerase cannot bind efficiently to its binding site in the lac promoter unless CAP/cAMP is already bound.
- The binding of the CAP/cAMP complex to its binding site in the lac promoter bends the DNA and makes it more accessible to RNA polymerase.
- At high Glc concentration, the cAMP level is very low; no CAP/cAMP complex is formed; RNA pol could not bind efficiently to the promoter; therefore, the lac operon is not fully induced even if lactose is present.
- At low Glc concentration, Adenylate cyclase gets activated and catalyzes rapid conversion of ATP into cAMP.
- cAMP is a hunger signaling molecule (secondary messenger) that binds to CAP to form the activator complex to fully induce the lac operon.
The promoter of lac operon
The lac promoter contains two separate sites, one for the RNA polymerase promoter and one for the CAP/cAMP complex. The CAP/cAMP complex must be present upstream of the RNA pol binding site in the lac promoter for the operon to be induced.
CAP/cAMP complex as positive control response
- The CAP/cAMP complex thus exerts positive control over the transcription of the lac operon. It has an effect exactly opposite to that of the repressor binding to an operator.
- In the absence of cAMP, CAP does not bind to the promoter. Thus, cAMP acts as an effector molecule determining the effects of CAP on lac operon transcription.
- The intracellular cAMP concentration is sensitive to the presence or absence of glucose. High concentrations of glucose cause a sharp decrease in the intracellular concentration of cAMP.
- Glucose prevents the activation of adenyl cyclase, the enzyme that catalyzes the formation of cAMP from ATP. Thus the presence of glucose results in a decrease in the intracellular concentration of cAMP.
- In the presence of a low concentration of cAMP, CAP cannot bind to the lac operon promoter. In turn, RNA polymerase can not bind efficiently to the lac promoter in the absence of bound CAP/cAMP.
- Thus in the presence of glucose, lac operon transcription never exceeds 2 percent of the induced rate observed in the absence of glucose.
In the absence of glucose and the presence of lactose
- The adenylate cyclase enzyme is activated causing a high level of cAMP
- CAP binds to the cAMP forming CAP/cAMP complex.
- CAP/cAMP complex then binds to the promoter stimulates RNA polymerase to bind to the promoter and initiates transcription.
- The presence of lactose causes the formation of an inducer (allolactose) inside the cell which binds to the repressor and inactivates it.
- Therefore, the operon is fully activated and induced in the absence of glucose and the presence of lactose.
