Carbonic anhydrase (CA) is an enzyme that assists rapid inter-conversion of carbon dioxide and water into carbonic acid, protons, and bicarbonate ions. It is abundant in all mammalian tissues. There are many genes that are inducible by hypoxia, via HIF-1 alpha. CA-9 is one of the most inducible genes because of its stability and location within the membrane. Carbonic anhydrases have a widespread role in regulating pH in normal tissues, by regulating hydrogen ion (H+) flux. The pH is important in cell death under hypoxia, thus a blockade of CA 9 results in increased cell death under hypoxia. Therefore, CA-9 has become a reliable histochemical marker of hypoxia.
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