Figure 4.

Contribution of carbonic anhydrases to tumor acidification. The cellular metabolism produces an excess of CO₂ that diffuses from the cell into the extracellular space. Membrane carbonic anhydrases IX and XII convert it in carbonic acid (CO₃H₂) through hydration. CO₃H₂ spontaneously ionizes into a molecule of ionized hydrogen (proton) that remains in the matrix, contributing to its acidification. The bicarbonate ion is reintroduced into the cell through the activity of the sodium bicarbonate cotransporter (NBC) contributing to cytoplasmic alkalinity.