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Carbonic anhydrase, enzyme is present in red blood cells, gastric mucosa, pancreatic cells, and renal tubules that acts as a catalyst in the interconversion of carbon dioxide (CO2) and carbonic acid (H2CO3). Carbonic anhydrase plays a significant role in respiration by influencing CO2 transport in the blood. The enzyme also has a significant role in the formation of hydrochloric acid in the stomach.
The active site for the carbonic anhydrase enzyme is taken to be a zinc ion, and it is thus classified as metalloenzymes. It has five distinct families.
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Key Terms: Carbonic Anhydrase, Enzyme, Catalysis, Bicarbonate, Carbon dioxide, metalloenzymes, Activation energy, Alpha Carbonic Anhydrase
What is Carbonic Anhydrase?
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Carbonic Anhydrase are zinc-containing metalloenzymes that catalyse the dehydration of bicarbonates and the hydration of carbon dioxide.
Carbonic Anhydrase
Other than its role in the transport of carbon dioxide, the enzyme also has a role in acid-base balance, regulation of pH, and maintaining fluid balance.
However, the exact function of the enzyme is subject to its location. In the stomach, carbonic anhydrase makes acid, ions. The bicarbonate ions have a role in maintaining water content in the eyes, in case of a build-up of fluid, it can cause glaucoma.
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Reactions of Carbonic Anhydrase
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The following reaction explains the catalysis of carbonic anhydrase in human tissues:
CO2 + H2O → H2CO3 → H+ + HCO3-
Catalyzation of the carbonic anhydrase in the lungs is denoted by:
H+ + HCO3- → H2CO3 → CO2 + H2O
The reason the reactions are in opposite directions for lungs and tissues is because of the variable pH levels found in these different locations. Without the carbonic anhydrase catalyst, this reaction is much slower; the reaction is 107 times faster in presence of the enzyme.
The reaction catalysed by the carbonic anhydrase is represented by:
HCO3- + H+ ⇋ CO2 + H2O
Because carbonic acid has a pKa of up to 6.36 (depending on the medium), a lower percentage of the bicarbonate can be protonated at pH 7.
Carbonic Anhydrase Reaction
Carbonic anhydrase, despite being one of the fast-reacting enzymes, is inhibited by the rate of diffusion of the substrates
Families of Carbonic Anhydrase
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There are five known distinct carbonic anhydrase families. Though they do not have any similarity in their amino acid sequence, it is taken as an example of convergent evolution. Carbonic anhydrase is classified as follows:
- Alpha-CA or α-CA
- Beta-CA or β-CA
- Gamma-CA or γ-CA
- Delta-CA or δ-CA
- Zeta-CA or ζ-CA
Structure of Carbonic Anhydrase
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Several forms of carbonic anhydrase are present in nature. In the best researched α-carbonic anhydrase form found in animals, the zinc2+ is bounded by the imidazole rings of 3 histidine residues.
Carbonic Anhydrase Structure
Functions of Carbonic Anhydrase
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Carbonic anhydrase like any enzyme works by lowering the activation energy of the substrate and thereby fastening the reactions.
Carbonic Anhydrase participates in Photosynthesis Process
Carbonic anhydrases are of crucial importance in several tissues:
- Parietal cells present in the stomach, secret huge amounts of acid in the form of hydrogen ions and protons in the lumen, and bicarbonate ions into the blood. The cells in the pancreatic duct work similarly, except their main secretory output is bicarbonate instead of hydrogen.
- Carbonic anhydrase catalyses bicarbonates to hydrogen ions, thus it helps in exhalation in the lungs.
- Carbonic anhydrase is also found in the renal tubules in the kidneys where it makes hydrogen ions which are vital for maintaining acid-base and fluid balance in the body.
- Carbonic anhydrase produces carbon dioxide in all cells by metabolism. The red blood cells remove it from the body. With the help of Carbonic anhydrase, the red blood cells convert a majority of CO2 to bicarbonate for transport. After that, the CO2 is exhaled out from the lungs.
- Carbonic anhydrase can also act as an inhibitor for therapeutic purposes. It is quite useful in the treatment of several conditions and for therapy for a few types of glaucoma.
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Mechanism of Carbonic Anhydrase
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The zinc ion in the Carbonic anhydrase is located in a cavity shaped like a cone, with three histidine side chains, and in the fourth position, there is a solvent molecule. But, a fourth histidine is situated near the water ligand which helps in the creation of the Zn-OH centre, where CO2 attaches itself resulting in the formation of zinc bicarbonate. The active site also features a pocket suitable for CO2, bringing it close to the hydroxide group.
Things to Remember
- Carbonic anhydrase is the fastest enzyme, and its rate is normally limited by the rate at which its substrates diffuse.
- The typical catalytic rates of the various forms of Carbonic anhydrase range from 104 -106 reactions per second.
- Carbonic anhydrase located in the lungs catalyses bicarbonate into carbon dioxide, which is ideal for exhalation.
- The active site of most carbonic anhydrases has a zinc ion. So, they are classified as metalloenzymes.
- Carbonic anhydrase maintains acid-base balance, maintains pH, and fluid balance.
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Sample Questions
Ques: What is the role of Carbonic anhydrase in gaseous transport? (2 marks)
Ans: Around 70% of CO2 is transported as sodium bicarbonate. CO2 diffuses into the blood plasma, a major chunk of it combines with water to form carbonic acid in the presence of carbonic anhydrase. Carbonic anhydrase is a zinc-containing enzyme that fastens the formation of carbonic acid. The carbonic acid breaks into bicarbonate (HCO3–) and hydrogen ions (H+).
Ques: How is CO2 transported in blood? (2 marks)
Ans: CO2 is transported in the blood in three forms.
Dissolved as gas in plasma: 7-10%
Bound to haemoglobin as carbaminohemoglobin in red blood cells: 20%
CO2 is present as bicarbonate ion in plasma and transported as bicarbonate: 70%
Ques: What is the role of Carbonic anhydrase involved in CO2 sequestration? (3 marks)
Ans: Carbonic anhydrase is the first discovered zinc-containing metalloenzyme that is present in animals, plants, and microorganisms that converts CO2 and water into bicarbonate. The Carbonic anhydrase is also present in diverse species of bacteria indicating that this enzyme plays a significant role in concentrating CO2. In photosynthetic assimilation of CO2, the Carbonic anhydrase enzyme acts as a biocatalyst. There is a potential role of the Carbonic anhydrase enzyme in solving environmental issues such as reducing carbon emissions through CO2 sequestration.
Ques: What is the Similarity of Cadmium-Containing Carbonic Anhydrase with Other Carbonic Anhydrases? (2 marks)
Ans: The mechanism of the Cadmium Carbonic Anhydrase (CDCA) is the same as other carbonic anhydrases in its conversion of carbon dioxide (CO2) and the water into proton and bicarbonate. Additionally, like the other carbonic anhydrases, CDCA also speeds up the reaction as its substrate's diffusion rate is inhibited by sulfamate and sulfonamide derivatives.
Ques: What is the role of the Carbonic anhydrase inhibitor? (3 marks)
Ans: Carbonic anhydrases are found in many nephron sites, predominantly in the luminal membrane of the proximal tubule cells. Carbonic anhydrase inhibitors suppress the activity of the enzymes, stopping the reabsorption of bicarbonate ions in the proximal tubule, which has several effects, like bicarbonate and potassium retention in the urine and reduces sodium absorption, acting as mild diuretics.
Ques: Write a note on the occurrence of Carbonic anhydrase in the animal kingdom. (3 marks)
Ans: Carbonic anhydrase does not have a single enzyme form, but a broad group of zinc metalloproteins enzymes that are found in three genetically unrelated families of isoforms (α, β, and γ). Carbonic anhydrases are found in almost all living organisms, from animals to plants, algae, and bacteria. At least 14 genetically distinct α-CA isozymes have been reported in human beings. These isozymes occur in different tissue distributions and intracellular locations.
Ques: Give the Transport of Cadmium? (3 marks)
Ans: Cadmium is thought to be lethal to phytoplankton in higher quantities. Research has also shown that T. weissflogii contains an initial toxic response to cadmium when exposed to it. The metal's toxicity is lowered by the translation and transcription of phytochelatin, which is the protein that binds and transports cadmium. Once they are bound by the phytochelatin, cadmium is no longer toxic, and also, it can be safely transported to the Carbonic anhydrase enzyme.
Ques: Role of Zinc in Carbonic anhydrase? (3 marks)
Ans: Carbonic anhydrase can be studied as the prototype of zinc enzymes which utilize the hydroxyl ion generated by ionisation of the Zn2+-OH2 as the nucleophile for hydrolysis or hydration reactions. The Zn2+ ion is present at the bottom of a conical cavity and is bonded to the protein by three invariant His residues, while the rest tetrahedral site is occupied by a water molecule. The water molecule makes a hydrogen bond with a Thr residue, which in turn makes hydrogen-bonded to a Glu residue.
Ques: Application of Carbonic anhydrase in medicine. (3 marks)
Ans: Carbonic Anhydrase acts as a target of interest at pharma company Merck, where they researched to design an inhibitor for topical use in the eye to treat glaucoma. Many carbonic anhydrase inhibitors were studied, those previously approved for clinical use as oral medications didn’t lower intraocular pressure on topical administration. It is still believed that a topically administered drug would not have the side effects associated with the use of oral medications.
Ques: What is Carbonic anhydrase Like Proteins? (3 marks)
Ans: Phytoplankton from various water sources were tested for Carbonic anhydrase presence. It was understood that a major chunk of them have proteins that are homologous to the Carbonic anhydrase found in T. weissflogii. The phytoplankton species from the Great Bay, New Jersey and in the Pacific Ocean, near the equator also had these enzymes. In all the studied species, Carbonic anhydrase-like proteins exhibited high expression levels even at high concentrations of zinc and in the absence of cadmium.
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