CAP and cAMP in the Lac Operon: Catabolite Repression Explained

The lac operon has two controls. The lac repressor turns it off when lactose is absent. CAP (catabolite activator protein, also called CRP) turns it up when glucose is scarce. CAP only activates when it is bound to cAMP, and cAMP is high only when glucose is low. That is the whole mechanism of catabolite repression.

The two signals

• Lactose signal (negative control). Allolactose, made from lactose, binds the repressor so it leaves the operator. Without lactose, the repressor sits on the operator and blocks RNA polymerase.
• Glucose signal (positive control). When glucose is low, cAMP rises. cAMP binds CAP. The CAP-cAMP complex binds a site upstream of the promoter and helps RNA polymerase bind, increasing transcription.

When glucose is high, cAMP is low, so CAP does not bind DNA and transcription stays low even if the repressor is off.

The four conditions

Only the last row gives strong transcription. The repressor must be off and CAP-cAMP must be bound.

Why this is useful to the cell

If both glucose and lactose are present, the cell uses glucose first and does not need to make the enzymes for lactose. Only when glucose runs out and lactose is present does it pay to make them. This is a form of diauxic growth: glucose is used first, then there is a pause, then lactose is used.

What cAMP is and is not

• cAMP is a signal of low glucose, not an inducer of the operon. The inducer is allolactose.
• cAMP is made by adenylate cyclase. In E. coli, glucose uptake lowers adenylate cyclase activity, so cAMP falls.
• Here cAMP works as a nutrient signal inside bacteria, binding CAP rather than acting through a receptor cascade.

Mutation logic

• CAP site mutated so CAP cannot bind: expression stays low even with lactose and low glucose.
• lacI mutated so the repressor cannot bind the operator: expression is constitutive but still reduced when glucose is high, because CAP is not helping.
• lacI mutated so the repressor cannot bind allolactose: the operon stays off in all conditions.

Common traps

• Saying CAP represses. CAP activates; the name catabolite repression refers to glucose's effect.
• Saying high cAMP means high glucose. It means low glucose.
• Forgetting the repressor. Low glucose alone does not turn the operon on.

One-minute recap

• Repressor off needs lactose. CAP active needs low glucose.
• Strong expression needs both.
• cAMP signals low glucose; allolactose is the inducer.