Carbonic anhydrase

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Carbonic anhydrase

Systematic name	carbonate hydrolyase
Other names	carbonate dehydratase; carbonate anhydrase; carbonic acid anhydrase
EC number	EC 4.2.1.1
CAS number	9001-03-0
EINECS	232-576-6
Disclaimer and references

Carbonic anhydrase (carbonate dehydratase) is a family of metalloenzymes (enzymes that contain one or more metal atoms as a functional component of the enzyme) that catalyze the rapid interconversion of carbon dioxide and water into carbonic acid, protons, and bicarbonate ions. This reaction occurs spontaneously in aqueous solution, but does so slowly.<ref>Badger MR, Price GD. 1994. The role of carbonic anhydrase in photosynthesis. Annu Rev Plant Physiol Plant Mol Biol. 45:369–392</ref> Carbonic anhydrase can greatly increase the rate of the reaction, with typical catalytic rates of the different forms of this enzyme ranging between 10⁴ and 10⁶ reactions per second <ref>Lindskog S. 1997. Structure and mechanism of carbonic anhydrase. PHARMACOLOGY & THERAPEUTICS. 74:1-20</ref>. The active site of most carbonic anhydrases contains a zinc ion.

1 Structure and function of CA
2 CA families
- 2.1 α-CA
- 2.2 β-CA
- 2.3 γ-CA
- 2.4 δ-CA
- 2.5 ε-CA
3 Pharmacological agents affecting CA
4 External link
5 References

[edit] Structure and function of CA

Several forms of carbonic anhydrase occur in nature. In the best studied α-carbonic anhydrase form present in animals, this zinc ion is coordinated by the imidazole rings of 3 histidine residues, His94, His96 and His119. 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. Plants contain a different form called β-carbonic anhydrase which is an evolutionarily 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 CO_{2_{within the chloroplast to increase the carboxylation rate of the enzyme Rubisco. This is the reaction which integrates CO_{2_{into organic carbon sugars during photosynthesis, and can only use the CO_{2_{form of carbon, not carbonic acid nor 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.

Reactions catalyzed by carbonic anhydrase:

<math>\rm CO_2 + H_2O \rightarrow^{Carbonic\ anhydrase} H_2CO_3</math> (in tissues - high CO₂ concentration)

<math>\rm H_2CO_3 \rightarrow^{Carbonic\ anhydrase} CO_2 + H_2O</math> (in lungs and nephrons of the kidney - low CO₂ concentration, in plant cells)

The reaction rate of carbonic anhydrase is among the fastest of all enzymes, and its rate is typically limited by the diffusion rate of its substrates.

[edit] CA families

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.

[edit] α-CA

The CA enzymes found in mammals are divided into four broad subgroups:

the cytosolic CAs (CA-I, CA-II, CA-III, CA-VII and CA XIII)
mitochondrial CAs (CA-VA and CA-VB)
secreted CAs (CA-VI)
membrane-associated CAs (CA-IV, CA-IX, CA-XII and CA-XIV)

[edit] β-CA

Most prokaryotic and plant chloroplast CAs belong to the beta family. Two signature patterns for this family have been identified:

C-[SA]-D-S-R-[LIVM]-x-[AP]
[EQ]-[YF]-A-[LIVM]-x(2)-[LIVM]-x(4)-[LIVMF](3)-x-G-H-x(2)-C-G

[edit] γ-CA

The gamma class of CAs come from methane-producing bacteria that grow in hot springs.

[edit] δ-CA

The delta class of CAs has been described in diatoms. The distinction of this class of CA has recently<ref name="Sawaya">Sawaya MR, Cannon GC, Heinhorst S, Tanaka S, Williams EB, Yeates TO, Kerfeld CA. 2006. The structure of beta-carbonic anhydrase from the carboxysomal shell reveals a distinct subclass with one active site for the price of two. J Biol Chem. 281(11):7546-55</ref> come into question, however.

[edit] ε-CA

The epsilon class of CAs occurs exclusively in bacteria in a few chemolithotrophs and marine cyanobacteria that contain cso-carboxysomes<ref>So AK, Espie GS, Williams EB, Shively JM, Heinhorst S, Cannon GC. 2004. A novel evolutionary lineage of carbonic anhydrase (epsilon class) is a component of the carboxysome shell. J Bacteriol. 186(3):623-30.</ref>. Recent 3-dimensional analyses<ref name="Sawaya"/> suggest that ε-CA bears some structural resemblance to β-CA, particularly near the metal ion site. Thus, the two forms may be distantly related, even though the underlying amino acid sequence has since diverged considerably.