Carbonic Anhydrase The Fastest Enzyme Biology Essay

centuryic Anhydrase The Fastest Enzyme biological science EssayCarbonic anhydrase, abbreviated as CA, is the first identified surface containing enzyme, (CA blowate hydro-lyase, EC 4.2.1.1) It is an enzyme that catalyzes the reversible hydration and dehydration of carbon dioxide to solve carbonous hot, bicarbonate ions and protons. Being one of the fastest enzyme known, it is believed that one subatomic particle of CA evoke process one million molecules of carbon dioxideper second. The basic molecular(a) structure of CA includes proper(postnominal) amino sort out acid threonine 199, glutamate 106, histidine 64 and histidine residues videlicet His 93, His 95, and His 118. The mode of regulation of CA is creation inhibited by diverse medically prescribed piths that act as non competitive inhibitors, an example is Acetazolamide. CA plays a major key type in the unstable ease and restrictive of pH in different parts of the body thus, alteration of this enzyme may lead to several diseases.(1)CARBONIC ANYHYDRASETHE START Breathing, a positive function in lifeThe air that we breathe in has around valuable oxygen, an important molecule wherein it helps the breakdown of fats and cultivated cabbages in our cells. From the blood, oxygen diffuses past binds with the hemoglobin to be transported in the cells of our body. A by product of sugar and fat breakdown in cells is called Carbon dioxide carbon dioxide). It is a key metabolite in all living organism and it needs to be removed from our body.Carbon dioxide is diffuse out of the cells and transported in the blood in different slipway to get to the lungs. CA is transported in numerous forms, in the first place as bicarbonate, HCO3-. hydrogen carbonate is a CO2- with an attached OH group. When the HCO3- reaches the lungs, it is transformed back to a CO2, so it sight be exhaled from the body. The conversion of bicarbonate to carbon dioxide facilitates its transport into the cell sequence the con version of carbon dioxide to bicarbonate assists trap the carbon dioxide in the cell. This interconversion of carbon dioxide and bicarbonate develop at a slow physiological pH hence organism tend to produces an enzyme to hasten the process. This enzyme trusty for the speed up interconversion, which can be found in the red blood cells, is called carbonic anhydrase. Although the interconversion of bicarbonate to carbon dioxide can happen without the enzyme, CA can swell increase the rate of the conversions up to a millions of fold. (2)STRUCTUREThe CA molecule in general has ellipsoidal shape with the estimated dimension 4.1 x 4.1 x 4.7 nm. The officious pose is situated in a cavity having an round conical shape. The cavity is assessed 1.5 m wide at the way in and about 1.6 nm deep attaining almost the center of the molecule. The surface ion is close to the peak of the cone and liganded into 3 imidazole groups. estimate 1. CA organise (2)Figure 1. shows the structure of CA. Tak en as a whole, is composed of 10-stranded anti-parallel beta-sheet cover with various elements of other tributary structure. The 6 alpha-helices and 10-beta sheets make up the secondary structure of carbonic anhydrase. The basic function of CA is basically to decide the oxygen and carbon dioxide content of the blood that is needed in a human body. As the function suggests, the chemical structure of CA ingrainedly lies with the presence of zinc that lies deep within its active voice site. Its common amino acid composition includes threonine, glutamate and histidine. The specificity of these 3 amino acids (threonine 199, glutamate 106, and histidine 64) plays a critical role in relation to the presence of zinc by charging it with a hydroxyl radical group ion. The zinc cation is associated with three histidine residue protein backbone namely His93, His95, and His118. As stated, zinc plays a major role in the reaction of CA. The zinc empower in the active perspective of CA is be ing move to body of water to be able to dissociate it into a proton and hydroxyl ion. The hydroxyl ion is being stabilized by the positively charged zinc, in this way the hydroxyl ion is being prep bed to attack the carbon dioxide internal the RBC.A approximate look with CA can be seen in the figure below where the amino acid chains in the active site unneurotic with the zinc are evident. The role of the zinc basically includes the command of electric chargeal transfer of the bound hydroxyl to the carbon dioxide to be able to form bicarbonate ion. From the figure, it shows that the intermediate structure where the bicarbonate ion is still attached to the enzyme. The alanine replicated the side chain for amino acid 199 in this arrangement. Histidine 64 swings in the direction of and away from the zinc ion in every cycle of enzyme action although it is portion the zinc to recharge with a novel hydroxyl ion. The two locations of this residue, revealed in the bottom right figur e, symbolize its movement throughout the action of enzyme. nigh immediately as the zinc is reloaded with an original water molecule in concert with the release of bicarbonate ion, the enzyme is set for another action on slightly new carbon dioxide molecule. (3)MECHANISM OF CATALYSISThe rate of catalysis of the CA is exceedingly pH dependent. It means that, the higher the pH, the catalysis is faster and as the pH reduces, the speed of the reaction falls down. The mean pH of this trans transition is near pH 7. (5)Figure 2. Mechanism of CA catalysis (6)Figure 2.0 shows the tool of CA catalysis. A zinc atom which is generally bound to four or more ligands differs in CA. In CA, three locations are occupied by imidazole ring of three histidine residues and an addendumal site is occupied by a water molecule. Thus the geometry form of the active site is tetrahedral. The zinc atom plays an important role in the mechanism of CA catalysis because it is responsible for the release of a pro ton H+ from a water molecule, which consequently generates a nucleophilic hydroxide ion. Then the carbon dioxide substratum will attach to the active site of the enzyme to react with the ion of hydroxide. The zinc-bound OH-attacks the carbon of CO2therefore converting it into a bicarbonate ion. This bechances since the zinc ion has the +2 charge, which attracts the oxygen of water. It then deprotonates the water, thus, converting it into a better nucleophile so that the newly converted hydroxyl ion can attack the carbon dioxide. After the nucleophilic attack of zinc bound OH-, addition of water molecule displaces the bicarbonate ion from the surface ion. The CA is then fructify for another cycle of catalysis. (7)KINETICS OF REACTIONSCA inhibitors are class of pharmaceuticals that get word the activity of carbonic anhydrase. It is inhibited by two classes of compounds, a metal complex forming anions and others are isosteres and sulfonamides. Inhibitors ionize upon binding with t he enzyme to give way an NH- group that relocates the zinc hydroxide ions and shares a hydrogen bond. There are roughly 25 clinically used CA inhibitors as a do medicatess. It is mainly established as antiglaucoma drugs, diuretics, hypotensive agents, anticonvulsants, anticancer agents, antiepileptics, with additional use in the management of duodenal and gastric ulcers, osteoporosis and neurological disorder. (8)AcetazolamideMethazolamideDorzolamideTopiramateFigure 3. Illustrations of somewhat CA inhibitors (9)Figure 3.0 shows some CA inhibitors like Acetozolamide which acts as a subdued diuretic. It cures glaucoma, altitude sickness, and some benign intracranial hypertension. Methazolamide calls glaucoma award in dogs which is called Open-angle glaucoma. time Topiramate which is a weak inhibitor, alleviate epilepsy, lennox gastuat syndrome and migraine headaches. And another CA inhibitor is the, Dorzolamide or sulphonamide which treat ocular hypertension or open-angele glau coma. (10)CA activator regulates the proton transfer processes among the active site and the solvent system. It besides binds at the entrance of the enzyme of the active site. 1 of the strong activator of CA is Histidine. Some amines and amino acids like l-Trp (tryptophan), l-Phe (Phenylalanine),d-DOPA (D- 3,4-dihydroxyphenylalanine),l-Tyr (Tyrosine), 4-amino-l-Phe also works as activators of CA. These CA activators are potentially target for drug development that can be useful as a differential for the enhancement of synaptic efficacy which can be able to treat various conditions like, depression, alzheimers disease, ageing, spatial learning and memory therapy enhancer. (11)MODE OF REGULATION Acetazolamide InhibitorIn case of intemperanceive contents of CA in blood and encircling(prenominal) areas of the lungs, proper regulation and inhibition is needed. Acetazolamide is a non competitive inhibitor that is effective in giving control with the catalytic reaction of the enzyme. This chemical complex substance is medically used o treat different conditions of moderate up to severe metabolic or respiratory alkalosis. Alkalosis may happen if excess CA is being reacted with the bicarbonate and carbon dioxide ions in the RBC, causing extreme absorption of bicarbonate thus giving the erythrocyte more basicity sooner than having enough and sufficient pH level. Acetazolamide action is explained by interfering with bicarbonate (HCO3-) reabsorption in the kidneys, thereby giving enough acidity in the RBC, and further results to alkalinizing the urine. The action of inhibition results further to decreased synthesis of aqueous humor of the eye and causes the lowering of intraocular pressure.The interaction of Acetazolamide with CA does not occur with the active site, only close or remote to the active site. The engagement effect of this inhibitor basically changes the shape of CA that obviously leads to the inability of the substratum to bind properly, results to n o catalytic reaction. (12)CARBONIC ANHYDRASE IN HEALTH AND ailmentCarbonic Anhydrase is found in numerous places in the body, including in the cerebro-spinal fluid, cytosol of some cells and mainly in the red blood cells. Since CA generates and utilizes protons and bicarbonate ions, it plays a major key role in the fluid balance and regulatory of pH in different parts of the body. Absence or version of the CA enzyme may lead to several diseases.Also, CA inhibitor contributes to several treatments of diseases.One of the linked diseases of CA is the Osteopetrosis with cerebral calcification and renal acidosis. It is a syndrome insufficient with CA in the body commonly called as Marble wit disease. This happens because sulfonamide inhibitor of CA can produce metabolic acidosis and have shown that CA inhibitors blocks the parathyroid hormone-induced the release of calcium bone which causes bone resorption. And since CA is present in the brain and CA inhibitors inhibits the production of cerebral spinal fluid, mutation of CA lead to cerebral calcification.Other disease associated with the deficiency of specific type of CAIII is the Myastenia gravis. It is an autoimmune neuromuscular disorder that results to a weak musclebuilder of a person. Defects in CA IV can cause retinitis pigmentosa, a degeneration of retinal photoreceptor, which a patient experiences night vision cecity and loss of midperipheral visual. (13)Glaucoma, a condition wherein a build up of fluid in the eyes occurs and this presses the optic impertinence that caused maltreat, is treated with the use of CA inhibitors like acetazolamide, brinzolamide, dorzolamide, and methazolamide. These inhibitors lessen the amount of fluid in the eye apace by 40% to 60% thus lowering the pressure inside the eye of a person with glaucoma. It now lessens the risk of optic nerve damage which promote vision loss. But prolong use of this drug affects the same enzyme in the tissue and may lead to kidney and liver damageThe CA also plays an important role in the secretion of acid through the catalyzed hydration of excreted CO2 in the stomach lining which is mainly responsible in digestion of food. It helps to make pancreatic juice alkaline and our saliva neutral. In summary, CA performs different role and functions at their specific locations. (14)