Ribbon diagram of human carbonic anydrase II, with zinc molecule visible in the center

The carbonic anhydrases (or carbonate dehydratases) form a family of enzymes that catalyze the rapid conversion of carbon dioxide to bicarbonate and protons, a reaction that occurs rather slowly in the absence of a catalyst. Ribbon diagrams, also known as Richardson Diagrams are 3D schematic representations of Protein structure and are one of the most common methods of protein depiction Enzymes are Biomolecules that catalyze ( ie increase the rates of Chemical reactions Almost all enzymes are Proteins Catalysis is the process in which the rate of a Chemical reaction is increased by means of a Chemical substance known as a catalyst Carbon dioxide ( Chemical formula:) is a Chemical compound composed of two Oxygen Atoms covalently bonded to a single In Inorganic chemistry, bicarbonate ( IUPAC -recommended nomenclature hydrogencarbonate) is an intermediate form in the Deprotonation In Chemistry, hydronium is the obsolete name for the Cation H 3 O + derived from Protonation of Water ^[1] The active site of most carbonic anhydrases contains a zinc ion; they are therefore classified as metalloenzymes. The active site of an Enzyme contains the catalytic and Binding sites. Zinc (ˈzɪŋk from Zink is a Metallic Chemical element with the symbol Zn and Atomic number 30 In Biochemistry, a metalloprotein is a generic term for a Protein that contains a Metal cofactor.

Structure and function of carbonic anhydrase

Several forms of carbonic anhydrase occur in nature. In the best-studied α-carbonic anhydrase form present in animals, the zinc ion is coordinated by the imidazole rings of 3 histidine residues, His94, His96 and His119. Histidine (abbreviated as His or H) is one of the 20 standard Amino acids present in Proteins In the Nutritional sense in

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. Plants are living Organisms belonging to the kingdom Plantae. In plants, carbonic anhydrase helps raise the concentration of CO₂ within the chloroplast in order to increase the carboxylation rate of the enzyme Rubisco. Chloroplasts are Organelles found in Plant cells and eukaryotic Algae that conduct Photosynthesis. Ribulose-15-bisphosphate carboxylase/oxygenase, most commonly known by the shorter name RuBisCO, is an Enzyme ( that is used in the Calvin cycle 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. Total organic carbon ( TOC) is the amount of Carbon bound in an Organic compound and is often used as a non-specific indicator of Water quality Photosynthesis is a Metabolic pathway that converts Light Energy into Chemical energy.

In 2000, a cadmium-containing carbonic anhydrase was found to be expressed in marine diatoms during zinc limitation. Diatoms ( Greek: (dia = "through" + (temnein = "to cut" i 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. Phytoplankton are the Autotrophic component of the Plankton community Before this discovery, cadmium has generally been thought of as a very toxic heavy metal without biological function. Cadmium (ˈkædmiəm is a Chemical element with the symbol Cd and Atomic number 48 As of 2005, this peculiar carbonic anhydrase form hosts the only known beneficial cadmium-dependent biological reaction.

The reaction catalyzed by carbonic anhydrase is:

(in tissues - high CO₂ concentration)^[2]

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. Tissue is a cellular organizational level intermediate between cells and a complete organism Diffusion is the net movement of particles (typically molecules from an area of high concentration to an area of low concentration by uncoordinated random movement Typical catalytic rates of the different forms of this enzyme ranging between 10⁴ and 10⁶ reactions per second. ^[3]

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.

(in lungs and nephrons of the kidney - low CO₂ concentration, in plant cells)

Mechanism

Close-up rendering of active site of human carbonic anhydrase II, showing three histidine residues (in pink) and a hydroxide group (red and white) coordinating the zinc ion (purple). lung is the essential Respiration organ in air-breathing Animals including most Tetrapods a few Fish and a few Snails The most primitive A nephron (from Greek νεφρός (nephros meaning "kidney" is the basic structural and functional unit of the Kidney. The kidneys are complicated organs that have numerous biological roles Histidine (abbreviated as His or H) is one of the 20 standard Amino acids present in Proteins In the Nutritional sense in In Chemistry, hydroxide is the most common name for the diatomic Anion OH− consisting of Oxygen and Hydrogen Zinc (ˈzɪŋk from Zink is a Metallic Chemical element with the symbol Zn and Atomic number 30 From PDB 1CA2. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography

A zinc prosthetic group in the enzyme is coordinated in three positions by histidine side chains. Zinc (ˈzɪŋk from Zink is a Metallic Chemical element with the symbol Zn and Atomic number 30 A prosthetic group is a non-protein (non- Amino acid) component of a Conjugated protein that is important in the protein's biological activity A side chain in Organic chemistry and Biochemistry is a part of a Molecule that is attached to a core structure 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.

A fourth histidine is placed close to the substrate of water and accepts a proton, in an example of general acid-general base catalysis. The proton ( Greek πρῶτον / proton "first" is a Subatomic particle with an Electric charge of one positive This leaves a hydroxide attached to the zinc. In Chemistry, hydroxide is the most common name for the diatomic Anion OH− consisting of Oxygen and Hydrogen

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.

CA families

Ribbon diagram of human carbonic anhydrase II. Active site zinc ion visible at center. The active site of an Enzyme contains the catalytic and Binding sites. Zinc (ˈzɪŋk from Zink is a Metallic Chemical element with the symbol Zn and Atomic number 30 From PDB 1CA2. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography

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. Peptide sequence or amino acid sequence is the order in which Amino acid residues connected by Peptide bonds lie in the chain in Peptides Convergent evolution describes the acquisition of the same biological trait in unrelated lineages The α-CAs are found in humans.

α-CA

The CA enzymes found in mammals are divided into four broad subgroups^[4], which, in turn consist of several isoforms:

• the cytosolic CAs (CA-I, CA-II, CA-III, CA-VII and CA XIII) (CA1, CA2, CA3, CA7, CA13)
• mitochondrial CAs (CA-VA and CA-VB) (CA5A, CA5B)
• secreted CAs (CA-VI) (CA6)
• membrane-associated CAs (CA-IV, CA-IX, CA-XII, CA-XIV and CA-XV) (CA4, CA9, CA12, CA14)

There are three additional "acatalytic" CA isoforms (CA-VIII, CA-X, and CA-XI) (CA8, CA10, CA11) whose functions remain unclear. Mammals ( class Mammalia) are a class of Vertebrate Animals characterized by the presence of Sweat glands, including sweat glands The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. Carbonic anhydrase II (gene name CA2) is one of fourteen forms of human α carbonic anhydrases. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. ^[5]

β-CA

Most prokaryotic and plant chloroplast CAs belong to the beta family. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. In Cell biology, a mitochondrion (plural mitochondria) is a membrane-enclosed Organelle found in most eukaryotic cells. The cell membrane (also called the plasma membrane, plasmalemma, or "phospholipid bilayer" is a Selectively permeable Lipid bilayer The active site of an Enzyme contains the catalytic and Binding sites. Cancer (medical term Malignant Neoplasm) is a class of Diseases in which a group of cells display uncontrolled The cytosol or intracellular fluid (or cytoplasmic matrix) is the liquid found inside cells. The active site of an Enzyme contains the catalytic and Binding sites. The kidneys are complicated organs that have numerous biological roles The heart is a muscular organ in all Vertebrates responsible for pumping Blood through the Blood vessels by repeated rhythmic Skeletal muscle is a type of Striated muscle, which usually attaches to tendons The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain The prokaryotes (proʊˈkærioʊts singular prokaryote /proʊˈkæriət/ are a group of Organisms that lack a Cell nucleus (= karyon or any other Chloroplasts are Organelles found in Plant cells and eukaryotic Algae that conduct Photosynthesis. 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

γ-CA

The gamma class of CAs come from methane-producing bacteria that grow in hot springs. In Genetics, a sequence motif is a Nucleotide or amino-acid Sequence pattern that is widespread and has or is conjectured to have a biological Methanogens are Archaea that produce Methane as a Metabolic byproduct in Anoxic conditions

δ-CA

The delta class of CAs has been described in diatoms. Diatoms ( Greek: (dia = "through" + (temnein = "to cut" i The distinction of this class of CA has recently^[7] come into question, however.

ε-CA

The epsilon class of CAs occurs exclusively in bacteria in a few chemolithotrophs and marine cyanobacteria that contain cso-carboxysomes. The Bacteria ( singular: bacterium) are a large group of unicellular Microorganisms Typically a few Micrometres in length bacteria have A lithotroph is an Organism that uses an Inorganic substrate (usually of mineral origin to obtain reducing equivalents for use in biosynthesis (e Cyanobacteria, also known as blue-green algae, blue-green bacteria or Cyanophyta, is a phylum of Bacteria that obtain their energy Carboxysomes are Bacterial microcompartments that contain enzymes involved in Carbon fixation. ^[8] Recent 3-dimensional analyses^[7] 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. Peptide sequence or amino acid sequence is the order in which Amino acid residues connected by Peptide bonds lie in the chain in Peptides

Pharmacological agents affecting CA

See Carbonic anhydrase inhibitors

External links

• PDB Molecule of the Month pdb49_1

References

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.