The primary function of the enzyme in animals is to interconvert carbon dioxide and bicarbonate to maintain acid-base balance in blood and other tissues, and to help transport carbon dioxide out of tissues.
There exist at least 14 different isoforms in mammals. Plants contain a different form called β-carbonic anhydrase, which, from an evolutionary standpoint, is a distinct enzyme, but participates in the same reaction and also uses a zinc ion in its active site. In plants, carbonic anhydrase helps raise the concentration of CO2 within the chloroplast in order to increase the carboxylation rate of the enzyme RuBisCO. This is the reaction that integrates CO2 into organic carbon sugars during photosynthesis, and can use only the CO2 form of carbon, not carbonic acid or bicarbonate.
In 2000, a cadmium-containing carbonic anhydrase was found to be expressed in marine diatoms during zinc limitation. In the open ocean, zinc is often in such low concentrations that it can limit the growth of phytoplankton like diatoms; thus a carbonic anhydrase using a different metal ion would be beneficial in these environments. Before this discovery, cadmium has generally been thought of as a very toxic heavy metal without biological function. As of 2005, this peculiar carbonic anhydrase form hosts the only known beneficial cadmium-dependent biological reaction.
The reaction catalyzed by carbonic anhydrase is:
The reaction rate of carbonic anhydrase is one of the fastest of all enzymes, and its rate is typically limited by the diffusion rate of its substrates. Typical catalytic rates of the different forms of this enzyme ranging between 104 and 106 reactions per second.
The reverse reaction is also relatively slow (kinetics in the 15-second range), which is why a carbonated drink does not instantly degas when opening the container, but will rapidly degas in one's mouth when carbonic anhydrase is added with saliva.
A zinc prosthetic group in the enzyme is coordinated in three positions by histidine side chains. The fourth coordination position is occupied by water. This causes polarisation of the hydrogen-oxygen bond, making the oxygen slightly more negative, thereby weakening it.
The active site also contains specificity pocket for carbon dioxide, bringing it close to the hydroxide group. This allows the electron rich hydroxide to attack the carbon dioxide, forming bicarbonate.
There are at least five distinct CA families (α, β, γ, δ and ε). These families have no significant amino acid sequence similarity and in most cases are thought to be an example of convergent evolution. The α-CAs are found in humans.
There are three additional "acatalytic" CA isoforms (CA-VIII, CA-X, and CA-XI) (, ) whose functions remain unclear.
|Isoform||Gene||Molecular mass||Location (cell)||Location (tissue)||Relative activity||Sensitivity to sulfonamides|
|CA-I||29 kDa||cytosol||red blood cell and GI tract||15%||high|
|CA-II||29 kDa||cytosol||almost ubiquitous||100%||high|
|CA-III||29 kDa||cytosol||8% of soluble protein in Type I muscle||1%||low|
|CA-IV||35 kDa||extracellularily GPI-linked||Widely distributed, e.g. acid-transporting||~100%||moderate|
|CA-VII||cytosol widely distributed in many cells and tissues|
|CA-XII||44 kDa||extracellularily located active site||certain cancers||~30%|
|CA-XIV||54 kDa||extracellularily located active site||kidney, heart, skeletal muscle, brain|
9. Lyall V, Alam RI, Phan DQ, Ereso GL, Phan TH, Malik SA, Montrose MH, Chu S, Heck GL, Feldman GM, DeSimone JA. Decrease in rat taste receptor cell intracellular pH is the proximate stimulus in sour taste transduction. Am J Physiol Cell Physiol. 2001 Sep;281(3):C1005-13.