Carbonic anhydrase (CA) is an enzyme that assists rapid interconversion of carbon dioxide and water into carbonic acid, protons, and bicarbonate ions. It is abundant in all mammalian tissues. Because of its functionality, it has become an important diagnostic marker for various cancers, most notably renal cell carcinoma (RCC). There are many genes that are inducible by hypoxia, via HIF-1 alpha. CA IX 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 IX results in increased cell death under hypoxia. Therefore, CA IX has become a reliable histochemical marker of hypoxia.
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