: Breathe in, Breathe Out Wauwatosa West SMART Team: Matt Berggruen, Ali Hassan, Jimmy Kralj, Kayla Lemmon, Emily Myers, and Mariah Rogers Advisor: Mary Anne Haasch Mentor: Dr. Dale Noel, Marquette University

Summary: Carbonic anhydrase is an that balances the pH of the and enables Abstract the out of dioxide. Diseases and Conditions

All animals breathe in oxygen and breath out (CO2). In red blood cells carbonic anhydrase catalyzes the reaction to convert carbon dioxide into Affected by Carbonic Carbonic anhydrase, which is found within red blood cells, catalyzes a carbonic , which further breaks down into ions and protons (H+). Anhydrase reaction converting CO and into , which The production of bicarbonate ions and protons regulates the pH of the blood, creating an 2 Carbonic anhydrase is an enzyme that dissociates into protons, and bicarbonate ions. Said to be “near environment in which your cells can live. also regulates the pH and fluid balances 6 perfection”, carbonic anhydrase is able to catalyze at a rate of 10 in numerous systems throughout the reactions per second. We modeled the alpha form, found in humans. body. The enzyme contains a pocket of amino His94, His96, and Within the kidneys and eyes, His119 that hold a ion. When a CO enters the of the Pocket, holding the bicarbonate ions and protons are 2 Zinc ion (bright pink), and the enzyme, it gains an OH- that was bonded to the zinc, forming produced in order to regulate the bicarbonate ion (bright green). amount of water within these organs. - carbonic acid that is then released. In order to replenish the OH , Carbonic anhydrase is what catalyzes water dissociates. The OH- binds to the zinc and the H+ is released. the reaction that makes this possible, so The reaction can now repeat itself. when it malfunctions, medical problems such as Glaucoma or failure can In the , carbonic anhydrase reverses the reaction, turning the occur. carbonic acid back into CO to be exhaled. This process also 2 Carbonic anhydrase has a role in maintains blood pH by controlling the amount of bicarbonate ions and regulating within the protons dissolved in the blood. stomach, and maintaining a neutral pH Malfunctions in carbonic anhydrase’s regulation can cause glaucoma, in , A malfunction in this area of the body causes ulcers. the second leading cause of blindness. This disorder can be treated with inhibitors of the enzyme that prevent over-secretion of fluid that To treat such diseases and conditions, presses on the optic nerve. Carbonic anhydrase inhibitors are also carbonic anhydrase inhibitors can be used to block the active site of the used to treat ulcers, neurological disorders, and osteoporosis. 1HCB.pdb enzyme and stop its use in certain areas in the body.

4. The bicarbonate is = Carbonic Anhydrase The reactions in steps 2 and 4 occur within a pocket of on carbonic anhydrase. This pocket is made of amino acids His94, converted back into - H2CO3 = Carbonic Acid His96, and His119 and holds a zinc ion bonded to the OH . CO2 and H2O by carbonic anhydrase H2CO3 - OH + CO2 H2CO3

2. Within a blood cell, H CO HCO - + H+ carbonic anhydrase 2 3 3 CO2 + H2O - converts the CO2 to HCO3 5. The CO2 in the 3. The H2CO3 breaks down into CO lungs is exhaled CO a proton (H+) and 2 2 H2CO3 a bicarbonate ion, Exhale lowering the blood pH. It is 1. CO2 waste from cells diffuses into - now transported OH + CO2 H2CO3 the bloodstream to the lungs.

A SMART Team project supported by the National Institutes of Health (NIH) – National Center for Research Resources Science Education Partnership Award (NCRR-SEPA) ; Kumar, Vinay and Kannan, K. (1994) Enzyme- Interactions, Structure of Human Carbonic Anhydrase I Complexed with Bicarbonate ; Dutta, Shuchismita and Goodsell, David (2004) PDB Molecule of the Month, Carbonic Anhydrase