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Carbonic anhydrase solubilizes carbon dioxide gas so we can breathe it out
Alpha (top), beta (middle), and gamma (bottom) carbonic anhydrases.
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Breathing In, Breathing Out
Breathing is a fundamental function in life - ever wondered what really happens when we breathe? The air we breathe in has precious oxygen that fuels the breakdown of sugars and fat in our cells. In our lungs, oxygen diffuses into the blood, binds to hemoglobin and is transported to all the cells of our body (see the Molecule of the Month feature on hemoglobin). Carbon dioxide is a byproduct of sugar and fat breakdown in cells and needs to be removed from our body. Again, blood acts as a transport medium. Carbon dioxide diffuses out of cells and is transported in blood in a few different ways: less than 10% dissolves in the blood plasma, about 20% binds to hemoglobin, while the majority of it (70%) is converted to carbonic acid to be carried to the lungs. An enzyme present in red blood cells, carbonic anhydrase, aids in the conversion of carbon dioxide to carbonic acid and bicarbonate ions. When red blood cells reach the lungs, the same enzyme helps to convert the bicarbonate ions back to carbon dioxide, which we breathe out. Although these reactions can occur even without the enzyme, carbonic anhydrase can increase the rate of these conversions up to a million fold.
Green Plants and Corals
Plants also use oxygen for producing energy, and also release carbon dioxide. Green plants can convert water and carbon dioxide into sugars in the presence of sunlight. This process, photosynthesis, uses carbon dioxide from the atmosphere. Gaseous carbon dioxide is stored in plants as bicarbonate ions. In both land and water plants, carbonic anhydrase plays a role in converting bicarbonate ions back to carbon dioxide for photosynthesis. Another interesting biological phenomenon where this enzyme plays a role is the calcification of corals. Seawater calcium reacts with the bicarbonate produced by carbonic anhydrase from the coral polyps, forming calcium carbonate. This is deposited as the hard exterior of corals.
Carbonic Anhydrases
Carbonic anhydrase is an enzyme that assists rapid inter-conversion of carbon dioxide and water into carbonic acid, protons and bicarbonate ions. This enzyme was first identified in 1933, in red blood cells of cows. Since then, it has been found to be abundant in all mammalian tissues, plants, algae and bacteria. This ancient enzyme has three distinct classes (called alpha, beta and gamma carbonic anhydrase). Members of these different classes share very little sequence or structural similarity, yet they all perform the same function and require a zinc ion at the active site. Carbonic anhydrase from mammals belong to the alpha class, the plant enzymes belong to the beta class, while the enzyme from methane-producing bacteria that grow in hot springs forms the gamma class. Thus it is apparent that these enzyme classes have evolved independently to create a similar enzyme active site. PDB entries 1ca2 , 1ddz and 1thj , shown here from top to bottom, are examples of the alpha, beta and gamma carbonic anhydrase enzymes, respectively. The zinc ions in the active site are colored blue in these figures. Note that the alpha enzyme is a monomer, while the gamma enzyme is trimeric. Although the beta enzyme shown here is a dimer, there are four zinc ions bound to the structure indicating four possible enzyme active sites. Other members of this class form tetramers, hexamers or octamers, suggesting that dimer is probably a building block for this class.
Mammalian carbonic anhydrases occur in about 10 slightly different forms depending upon the tissue or cellular compartment they are located in. These isozymes have some sequence variations leading to specific differences in their activity. Thus isozymes found in some muscle fibers have low enzyme activity compared to that secreted by salivary glands. While most carbonic anhydrase isozymes are soluble and secreted, some are bound to the membranes of specific epithelial cells. For a deeper look at carbonic anhydrase from a genomic perspective, please visit the Protein of the Month feature at the European Bioinformatics Institute.
Inhibitor (green) bound in the active site of carbonic anhydrase.
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Carbonic Anhydrase in Health and Disease
Since this enzyme produces and uses protons and bicarbonate ions, carbonic anhydrase plays a key role in the regulation of pH and fluid balance in different parts of our body. In our stomach lining it plays a role in secreting acid, while the same enzyme helps to make pancreatic juices alkaline and our saliva neutral. The transport of the protons and bicarbonate ions produced in our kidney and eyes influence the water content of the cells at these locations. Thus carbonic anhydrase isozymes perform different functions at their specific locations, and their absence or malfunction can lead to diseased states, ranging from the loss of acid production in the stomach to kidney failure.
When there is a build up of fluid that maintains the shape of our eyes, the fluid often presses on the optic nerve in the eye and may damage it. This condition is called glaucoma. In recent years, inhibitors of carbonic anhydrase are being used to treat glaucoma. Blocking this enzyme shifts the fluid balance in the eyes of the patient to reduce fluid build up thereby relieving pressure. The structure of PDB entry 1cnw shows how one such inhibitor (a sulfonamide), colored green in the figure, is bound to human carbonic anhydrase (isozyme II). Note that this inhibitor binds near the active site and disrupts the interactions of the water bound to the zinc ion, blocking the enzyme action. Unfortunately, prolonged use of this drug can affect the same enzyme present in other tissues and lead to side effects like kidney and liver damage.
Exploring the Structure
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Carbonic Anhydrase in Action
The alpha carbonic anhydrase enzymes have been well studied, leading to an understanding of how they work. Three structures are shown here, showing three steps in the process. The structure at the top (PDB entry 5dsj) is the empty enzyme. The active site includes a zinc ion (magenta), which is held by three histidines (purple). The zinc also coordinates a hydroxide ion (red). At bottom left (PDB entry 5dsi), carbon dioxide (red and gray) is bound and a glutamate and a threonine (green) assist with the reaction. At bottom right (PDB entry 1cam), the hydroxide has been added, forming carbonic acid. The threonine has been mutated to alanine to help capture the complex. The histidine at upper left (green), which was seen in two different conformations in the structure, assists with guiding one of the nearby water molecules (orange) to the zinc ion, and converting it to a hydroxyl. To explore these three structures in more detail, click on the image for an interactive JSmol.
Topics for Further Discussion
- Carbonic anhydrase is an example of a "perfect" enzyme, which performs its reaction as fast as carbon dioxide molecules can diffuse to it. You can find other diffusion-limited enzymes in the PDB archive, including catalase, superoxide dismutase, and triosephosphate isomerase.
Related PDB-101 Resources
- Browse You and Your Health
- Browse Enzymes
- Browse Biology of Plants
References
- 5dsi, 5dsj: Kim JK, Lomelino CL, Avvaru BS, Mahon BP, McKenna R, Park SY & Kim CU (2018) Active-size solvent replenishment observed during human carbonic anhydrase II catalysis. IUCrJ 5, 93-102.
- BC Tripp, K Smith & JG Ferry (2001) Carbonic anhydrase: New insights for an ancient enzyme. Journal of Biological Chemistry 276, 48615-48618.
- 1ddz: S Mitsuhashi, T Mizushima, E Yamashita, M Yamanoto, T Kumasaka, H Moriyama, T Ueki, S Miyachi & T Tsukihara (2000) X-ray structure of beta-carbonic anhydrase from the red alga, Porphyridium purpureum, reveals a nove catalytic site for CO(2) hydration. Journal of Biological Chemistry 275, 5521-5526.
- S Lindskog (1997) Structure and Mechanism of Carbonic Anhydrase. Pharmacology and Therapeutics 74, 1-20.
- 1thj: C Kisker, H Schindelin, BE Alber, JG Ferry & DC Rees (1996) A left-hand beta-helix revealed by the crystal structure of a carbonic anhydrase from the archaeon Methanosarcina thermophila. EMBO Journal 15, 2323-2330.
- 1cnw: PA Boriack, DW Christianson, J Kingery-Wood & GM Whitesides (1995) Secondary interactions significantly removed from the sulfonamide binding pocket of carbonic anhydrase II influence inhibitor binding constants. Journal of Medicinal Chemistry 38, 2286-2291.
- 1ca2: AE Eriksson, TA Jones & A Liljas (1988) Refined structure of human carbonic anhydrase II at 2.0 A resolution. Proteins. 4, 274-282.
January 2004, Shuchismita Dutta, David Goodsell
About Molecule of the Month
The RCSB PDB Molecule of the Month by David S. Goodsell (The Scripps Research Institute and the RCSB PDB) presents short accounts on selected molecules from the Protein Data Bank. Each installment includes an introduction to the structure and function of the molecule, a discussion of the relevance of the molecule to human health and welfare, and suggestions for how visitors might view these structures and access further details.More
FAQs
What is PDB molecule of the month carbonic anhydrase? ›
Carbonic anhydrase is an enzyme that assists rapid inter-conversion of carbon dioxide and water into carbonic acid, protons and bicarbonate ions. This enzyme was first identified in 1933, in red blood cells of cows. Since then, it has been found to be abundant in all mammalian tissues, plants, algae and bacteria.
What is carbonic anhydrase summary? ›Carbonic anhydrase is a metalloenzyme that accelerates the interconversion between CO2 and H2O, and H2CO3 (carbonic acid) and its dissociative ions (HCO3− and H+). Carbonic anhydrase regulates pH and assists in the transport of CO2.
Where do you find carbonic anhydrase quizlet? ›Carbonic anhydrase is found in blood and saliva (1st, 2:06).
What molecules are in carbonic anhydrase? ›Carbonic anhydrase (CA; carbonate hydro-lyase, EC 4.2. 1.1) is a zinc-containing enzyme that catalyzes the reversible hydration of carbon dioxide: CO2+ H2O<-->HCO3(-)+H+. The enzyme is the target for drugs, such as acetazolamide, methazolamide, and dichlorphenamide, for the treatment of glaucoma.
Where can I find carbonic anhydrase? ›Carbonic anhydrase (CA) II is found in renal tubules, brain, and osteoclasts, and is critical in acid-base homeostasis and bone remodeling (McMahon et al., 2001; Lehenkari et al., 1998).
What is carbonic anhydrase and what is its function? ›Carbonic anhydrases (CAs) catalyze a reaction fundamental for life: the bidirectional conversion of carbon dioxide (CO2) and water (H2O) into bicarbonate (HCO3-) and protons (H+). These enzymes impact numerous physiological processes that occur within and across the many compartments in the body.
Why is carbonic anhydrase important? ›Carbonic anhydrase plays an important role in respiration by influencing CO2 transport in the blood. The enzyme also functions in the formation of hydrochloric acid by the stomach.
What is an example of a carbonic anhydrase? ›Acetazolamide, dichlorphenamide, and methazolamide are carbonic anhydrase inhibitors.
What is carbonic anhydrase an example of *? ›Carbonic anhydrase is an example of lyase which also helps in the breakdown reaction without hydrolysis. Carbonic anhydrase is an enzyme that helps in the conversion of the carbon dioxide and water into carbonic acid without the aid of hydrolysis. It also converts the protons into the bicarbonate ions.
What is carbonic anhydrase responsible for _____? ›Carbonic anhydrase helps maintain acid–base homeostasis, regulate pH, and fluid balance.
What is the enzyme called carbonic anhydrase? ›
Carbonic anhydrase (CA) is a thoroughly studied enzyme. Its primary role is the rapid interconversion of carbon dioxide and bicarbonate in the cells, where carbon dioxide is produced, and in the lungs, where it is released from the blood. At the same time, it regulates pH homeostasis.
What is the function of the carbonic anhydrase quizlet? ›What is the function of Carbonic Anhydrase? Carbonic Anhydrase catalyzes a reaction that joins carbon dioxide and water to form carbonic acid that generates bicarbonate ions and transfers CO2 into the blood plasma.
What type of protein is carbonic anhydrase? ›Abstract. The catalytically inactive isoforms of α-carbonic anhydrases are known as carbonic anhydrase related proteins (CARPs). The CARPs occur independently or as domains of other proteins in animals (both vertebrates and invertebrates) and viruses.
How many types of carbonic anhydrase are there? ›There are currently five (alpha, beta, gamma, delta, zeta) classes of carbonic anhydrases (CA's) of which the alpha-class from mammalian sources has been studied to a much greater extent compared to the other four classes.
Do humans have carbonic anhydrase? ›They occur in various tissues in the cytoplasm, cell membrane, and mitochondria, or as extracellular enzymes (e.g., breast milk) [6]. Carbonic anhydrases (CAs) are almost ubiquitously present in human cells.
Where do you get carbonic acid? ›Carbonic acid can be found in nature as in the oceans or in caves. Carbonic acid can also be made through industry such as in the making of carbonated beverages or through industrial fermentation or by the burning of fossil fuels.
What is the most efficient carbonic anhydrase? ›Among them, carbonic anhydrase II (CA II) is one of the most efficient known enzymes, with catalytic efficiencies close to the diffusion limit, with kcat/Km = 1.5 × 108 M− 1 s− 1.17–21 Of note, carbonic anhydrase was the first zinc enzyme for which inhibitors were developed.
What does carbonic anhydrase do for the liver? ›Carbonic anhydrases promote fatty acid synthesis in adipocytes and the liver [12, 13, 14]. In addition, the expression of carbonic anhydrase 3 (CA3) enhances fat accumulation during the process of differentiation from preadipocytes to adipocytes.
Is carbonic anhydrase a protein? ›Carbonic anhydrase (CA, EC 4.2. 1.1) is a protein that is especially well-suited to serve as a model in many types of studies in biophysics, bioanalysis, the physical-organic chemistry of inhibitor design, and medicinal chemistry.
What diseases are related to carbonic anhydrase? ›Carbonic anhydrase inhibitors are a medication used to manage and treat glaucoma, idiopathic intracranial hypertension, altitude sickness, congestive heart failure, and epilepsy, among other diseases. Carbonic anhydrase inhibitors are considered part of the diuretic class of medications.
What would happen if we didn't have carbonic anhydrase? ›
What would happen if no carbonic anhydrase were present in red blood cells? If no carbonic anhydrase were present in red blood cells then carbon dioxide would not be hydrolyzed into carbonic acid or bicarbonate.
What would happen if the body stopped producing carbonic anhydrase? ›If the enzyme was not made in the body, then carbon dioxide would be transported in the blood without being converted into bicarbonate ions. This would cause the pH of the plasma to decrease (i.e. become more acidic).
What are the symptoms of carbonic anhydrase? ›These potentially life-threatening episodes can cause poor feeding, vomiting, weight loss, tiredness (lethargy), rapid breathing (tachypnea), seizures, or coma.
What is carbonic anhydrase for dummies? ›Carbonic anhydrase functions to turn carbon dioxide and water into carbonic acid. The carbonic acid is then catalyzed to hydrogen ions and bicarbonate. The reaction is necessary to transfer ions and gases throughout the body to a form that can be absorbed or eliminated as waste.
What is the fastest enzyme in the body? ›Final answer: Carbonic Anhydrase is the name of fastest enzyme.
Where is the enzyme carbonic anhydrase used? ›An enzyme present in red blood cells, carbonic anhydrase, aids in the conversion of carbon dioxide to carbonic acid and bicarbonate ions.
What does carbonic anhydrase regulates the formation of? ›Carbonic anhydrases (CAs) are zinc metalloenyzmes that catalyze the reversible conversion of carbon dioxide to carbonic acid and are involved in respiration, calcification, acid-base balance, and formation of fluids.
Where is high concentration of carbonic anhydrase found? ›Carbonic anhydrase is found in the blood, gastric mucosa and the minute quantity of same is in plasma. The carbonic anhydrase enzymes work to catalyze the conversion of carbon dioxide and water to the dissociated ions of carbonic acid. This produces bicarbonate anions which get dissolved in the blood plasma.
Which best describes the action of carbonic anhydrase? ›Which best describes the action of carbonic anhydrase? It converts carbon dioxide and water to carbonic acid which dissociates into bicarbonate and hydrogen ions.
Where is carbonic anhydrase found in red blood cells? ›CARBONIC anhydrase, which catalyses the reversible reaction CO2 + H2 ⇄ H2CO3, is an intracellular enzyme found in high concentration within red blood corpuscles1.
What is the role of carbonic anhydrase in transport of CO2 in blood? ›
[2] Most of the carbon dioxide diffusing through the capillaries and ultimately into the red blood cells combines with water via a chemical reaction catalyzed by the enzyme carbonic anhydrase catalyzes, forming carbonic acid. Carbonic acid almost immediately dissociates into a bicarbonate anion (HCO3-) and a proton.
What is the role of carbonic anhydrase enzyme in urine physiology? ›Carbonic anhydrase (CA) catalyzes the reversible hydration of CO(2). CA is expressed in most segments of the kidney. CAII and CAIV predominate in human and rabbit kidneys; in rodent kidneys, CAXII, and CAXIV are also present. CAIX is expressed by renal cell carcinoma (RCC).
What is the role of carbonic anhydrase in parietal cells? ›Abstract. Experimental studies located carbonic anhydrase (CA) in the parietal cells close to secretory canaliculi, in superficial epithelial cells and gastric microvasculature. The role of CA is CO2 hydration resulting H+ for acid secretion and conversion of OH into HCO3-.
Why is carbonic anhydrase the fastest enzyme? ›Carbonic anhydrase is one of the fastest enzymes while lysozyme is the slowest enzyme. One molecule of carbonic anhydrase enzyme can hydrate 106 molecules of CO2 per second. This reaction is 107 times faster than reactions that take place in the absence of carbonic anhydrase.
What is the molecular mass of carbonic anhydrase? ›Description. Carbonic anhydrase 2 Human Recombinant protein produced in E. Coli containing 260 amino acids (1-260) and having a molecular mass of 29.2 kDa.
What is the PDB code for Rubisco? ›RCSB PDB - 1GK8: Rubisco from Chlamydomonas reinhardtii.
What is luciferase protein PDB? ›Firefly luciferase is a 62 kDa protein that catalyzes the production of light. In the presence of MgATP and molecular oxygen, the enzyme oxidizes its substrate, firefly luciferin, emitting yellow-green light. The reaction proceeds through activation of the substrate to form an adenylate intermediate.
What is carbonic anhydrase involved in? ›carbonic anhydrase, enzyme found in red blood cells, gastric mucosa, pancreatic cells, and renal tubules that catalyzes the interconversion of carbon dioxide (CO2) and carbonic acid (H2CO3). Carbonic anhydrase plays an important role in respiration by influencing CO2 transport in the blood.
Where is carbonic anhydrase found in high concentration in blood? ›Carbonic anhydrase is found in the blood, gastric mucosa and the minute quantity of same is in plasma. The carbonic anhydrase enzymes work to catalyze the conversion of carbon dioxide and water to the dissociated ions of carbonic acid. This produces bicarbonate anions which get dissolved in the blood plasma.
What is a protein PDB 101? ›PDB-101 is an online portal for exploring the world of proteins and nucleic acids. The diverse shapes and functions of biological macromolecules help explain all aspects of biomedicine and agriculture, from protein synthesis to health and disease to biological energy.
What is the PDB ID for carbonic anhydrase? ›
RCSB PDB - 1H9N: H119N CARBONIC ANHYDRASE II.
What is a PDB number? ›Every experimental structure in the PDB is assigned a 4-character alphanumeric identifier called the PDB identifier or PDB ID (e.g., 2hbs). In some cases, large groups of structures (e.g., a protein bound to a series of different inhibitors/drugs) are submitted to the PDB.
What is human luciferase enzyme? ›Luciferase is a generic term for the class of oxidative enzymes that produce bioluminescence, and is usually distinguished from a photoprotein. The name was first used by Raphaël Dubois who invented the words luciferin and luciferase, for the substrate and enzyme, respectively.
What is antibody for luciferase? ›Anti-Luciferase pAb is a goat polyclonal antibody designed for use in immunocytochemistry and Western blot applications. Anti-Luciferase pAb can detect luciferase enzyme expression in situ. Western blotting (1μg/ml).
What does PDB stand for protein? ›The Protein Data Bank (PDB; http://www.rcsb.org/pdb/ ) is the single worldwide archive of structural data of biological macromolecules.
Is carbonic anhydrase an enzyme in the human body? ›Carbonic anhydrases constitute a group of enzymes that catalyse reversible hydration of carbon dioxide leading to the formation of bicarbonate and proton. The platelet carbonic anhydrase II (CAII) was described for the first time in the '80s of the last century.
How does carbonic anhydrase affect blood pH? ›Carbonic anhydrase inhibition decelerates the initial acidification and attenuates the associated transient vasoconstriction without affecting intracellular pH or artery tone at steady-state.