How Does Carbonic Anhydrase Regulate Acid-Base Balance?
Carbonic anhydrase is defined as an enzyme. It is found in red blood cells, pancreatic cells, gastric mucosa, and the renal tubules that catalyze the interconversion of carbonic acid (H2CO3) and carbon dioxide (CO2).
Carbonic anhydrase plays an essential role in respiration by influencing CO2 transport in the blood. This enzyme also functions in the hydrochloric acid formation by the stomach.
Carbonic anhydrase enzyme helps to maintain acid-base homeostasis, fluid balance and regulate pH. Based on its location, the enzyme role changes slightly. For example, carbonic anhydrase forms acid in the stomach lining.
Structure and Function
Many forms of carbonic anhydrase take place in nature. The zinc ion can be coordinated by the imidazole rings of three histidine residues, His94, His96, and His119, in the best-studied, -carbonic anhydrase shape, which is present in animals.
The major enzyme function in animals is to interconvert the bicarbonate and carbon dioxide to maintain acid-base balance in the blood and other tissues and also to help transport carbon dioxide out of the tissues.
At least, there are 14 different isoforms in mammals. At the same time, plants have a different form, known as β-carbonic anhydrase, that from an evolutionary standpoint, which is a distinct enzyme. However, it participates in a similar reaction and also uses a zinc ion in its active site. Carbonic anhydrase in plants helps to increase the carboxylation rate of the RuBisCO enzyme by increasing the concentration of CO2 within the chloroplast. This reaction integrates CO2 into the organic carbon sugars during the photosynthesis process and can use only CO2 form of carbon, but not carbonic acid or bicarbonate.
Reaction
The following reaction illustrates the catalysis of carbonic anhydrase in our tissues:
CO2 + H2O → H2CO3 → H+ + HCO-3
Catalyzation of the carbonic anhydrase in the lungs is represented by:
H+ + HCO-3 → H2CO3 → CO2 + H2O
The reaction's reason being in the opposite directions for lungs and tissues is because of the variable pH levels found in them. Without the carbonic anhydrase catalyst, however, this reaction is much slower; with the catalyst, the reaction is 107 times faster.
The reaction, which is catalyzed by the carbonic anhydrase is given by:
HCO-3 + H+ ⇋ CO2 + H2O
Since 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 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 this enzyme range from 104 -106 reactions per second.
The uncatalyzed reverse reaction is said to be relatively slow (in the range of 15-second for kinetics). This is the reason why a carbonated drink does not instantly degas while opening the container when it comes into contact with the carbonic anhydrase found in saliva, however, it quickly degasses in the mouth.
An anhydrase can be defined as an enzyme, which catalyzes the water molecule removal from a compound, and so, it is the "reverse" reaction, which gives the carbonic anhydrase its name because it removes water a molecule from the carbonic acid.
Carbonic anhydrase in the lungs transforms bicarbonate into carbon dioxide, which is ideal for exhalation.
Mechanism
A zinc prosthetic group, which exists in the enzyme, can be coordinated in 3 positions by histidine side-chains. The 4th coordination position is taken place by the water. A 4th histidine is close to the water ligand by facilitating the formation of the Zn-OH centre, which binds CO2 to produce zinc bicarbonate. An example of general acid is the construct, which is a general base catalysis. Also, the active site features a pocket suited for carbon dioxide by bringing it close to a hydroxide group.
It is an enzyme of carbonic anhydrase in red blood cells or carbonic anhydrase in RBC.
The active site of human carbonic anhydrase II is depicted in the diagram below, with three histidine residues and one hydroxyl group coordinating (dashed lines) the zinc ion in the middle. From PDB: 1CA2.
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Cadmium-Containing Carbonic Anhydrase
Marine diatoms have been found to express the new form of ζ carbonic anhydrase. The T. weissflogii, which is a species of phytoplankton common to several marine ecosystems, was found to have carbonic anhydrase with a cadmium ion in place of zinc. In previous days, it had been believed that cadmium was one of the toxic metals with zero biological function whatsoever.
However, this phytoplankton species appears to have adapted to the low zinc levels in the ocean using cadmium when there is no presence of enough zinc. Since the concentration of cadmium in seawater is poor (up to 1x1016 molar), there is an environmental gain of being able to use any metal depending on how much is available at the time. Therefore, this type of carbonic anhydrase is cambialistic, which means that it can interchange the metal in its active site with the other metals, namely, cadmium and zinc.
FAQs on Carbonic Anhydrase: Structure, Function, and Significance
1. What is the primary function of the enzyme carbonic anhydrase in the body?
The primary function of carbonic anhydrase is to catalyse the rapid interconversion of carbon dioxide (CO₂) and water (H₂O) into bicarbonate (HCO₃⁻) and protons (H⁺). This reaction is crucial for various physiological processes, including the transport of CO₂ in the blood from tissues to the lungs and maintaining acid-base balance.
2. What is the chemical reaction catalysed by carbonic anhydrase?
Carbonic anhydrase catalyses the following reversible chemical reaction: CO₂ + H₂O ⇌ H₂CO₃ ⇌ H⁺ + HCO₃⁻. The direction of the reaction depends on the location in the body. In tissues with high CO₂ levels, the reaction proceeds to the right to form bicarbonate for transport. In the lungs, where CO₂ levels are low, the reaction shifts to the left to release CO₂ for exhalation.
3. Why is carbonic anhydrase considered one of the fastest enzymes known?
Carbonic anhydrase is exceptionally fast because of its high catalytic efficiency. It can hydrate up to 10⁶ (one million) molecules of CO₂ per second. This incredible speed is essential for the rapid exchange of gases in the blood as it passes through respiratory capillaries, a process that takes less than a second.
4. To which class of enzymes does carbonic anhydrase belong?
Carbonic anhydrase belongs to the class of enzymes known as Lyases. Specifically, it is a hydro-lyase (EC 4.2.1.1). Lyases are enzymes that catalyse the breaking of various chemical bonds by means other than hydrolysis and oxidation, often forming a new double bond or a new ring structure.
5. How does the structure of carbonic anhydrase contribute to its catalytic activity?
The structure of carbonic anhydrase is key to its function. Its active site contains a zinc ion (Zn²⁺), which is essential for catalysis. This zinc ion is coordinated by three histidine residues and a water molecule. It polarises the bound water molecule, making it a potent nucleophile that attacks the carbon dioxide molecule, thus facilitating the reaction. This makes carbonic anhydrase a classic example of a metalloenzyme.
6. Where is carbonic anhydrase found in the human body?
Carbonic anhydrase is found in various locations throughout the human body, each with a specific function. Key locations include:
- Red Blood Cells: For the efficient transport of carbon dioxide from tissues to the lungs.
- Kidney Tubules: To regulate the pH of blood and urine by managing bicarbonate reabsorption.
- Gastric Mucosa: To aid in the secretion of hydrochloric acid in the stomach.
- Pancreas: To assist in the production of bicarbonate-rich pancreatic juice.
7. What happens if the function of carbonic anhydrase is inhibited?
Inhibiting carbonic anhydrase disrupts the critical physiological processes it manages. Carbonic anhydrase inhibitors, such as the drug acetazolamide, block the enzyme's activity. This can lead to:
- Reduced secretion of aqueous humour in the eye, which is used to treat glaucoma.
- Increased excretion of bicarbonate by the kidneys, which can help treat altitude sickness and act as a diuretic.
- An accumulation of CO₂ in tissues, leading to acidosis.
8. How is carbonic anhydrase relevant to carbon capture technology?
The high efficiency of carbonic anhydrase in converting CO₂ to bicarbonate makes it a subject of research for carbon capture and storage (CCS) technologies. By mimicking or directly using this enzyme, industrial processes can accelerate the capture of CO₂ from flue gases, converting it into a more stable and storable form like bicarbonate, thus helping to mitigate greenhouse gas emissions.
