catabolite repression (CAP-cAMP)

Suppose you keep a premium credit card and a coupon for a cheap meal. As long as the good card works, you ignore the coupon. Only when the card is declined do you bother digging out the coupon. A bacterium treats glucose like that premium card: while glucose is available it barely bothers with other sugars, and only when glucose runs low does it switch on the genes for the alternatives. Catabolite repression is the system that enforces this 'glucose first' priority.

Here is the mechanism, which is the positive-control half of the lac story. The cell senses how much glucose it has indirectly, through the level of a small signalling molecule called cyclic AMP (cAMP): when glucose is scarce, cAMP rises; when glucose is plentiful, cAMP falls. A protein called CAP (catabolite activator protein, also known as CRP) only becomes active when cAMP binds it. Active CAP-cAMP then binds a site just upstream of the lac promoter and helps RNA polymerase settle there, boosting transcription. So when glucose is low, cAMP is high, CAP-cAMP is bound, and the promoter is strong; when glucose is high, cAMP is low, CAP-cAMP is gone, and the promoter is weak even if the repressor has already left. This is genuine positive control: an activator that helps rather than blocks.

Combine this with the repressor and you get the lac operon's logic gate. The operon fires strongly only when lactose is present (so the repressor is off the operator) AND glucose is absent (so CAP-cAMP is on the promoter). Either signal alone gives only weak output. This is one of the first and clearest cases of a cell computing a simple logical AND from two environmental inputs. A note of honesty: in many bacteria the glucose effect also works through other routes (such as inducer exclusion, which keeps lactose out while glucose is around), so cAMP-CAP is the famous part of catabolite repression but not the whole story.