Carbonic anhydrase is an important enzyme that regulates the acid-base balance of an organism. In fact, carbonic anhydrase (CA) is so important to homeostasis, it is found in all living organisms studied to date – from microorganisms (like bacteria) to mammals. As the name implies, this enzyme is responsible for catalyzing the hydration of carbon dioxide, which is a reversible process (see figure above). In other words, it speeds up the rate at which carbon dioxide and water combine (and the reverse reaction). This process creates acid (H+) and bicarbonate (HCO3-). Hence, its ability to regulate the pH of an organism.
Carbonic anhydrase was the subject of an article published in Physiological Reviews, which highlighted the known functions of this enzyme as well as research aimed at exploring its roles in various pathologies across organisms. Aside from regulating pH, various forms of carbonic anhydrase play a role in the ability to taste foods, the ability for sperm to move, the production and secretion of enzymes responsible for digesting foods, bone remodeling, cognition, muscle coordination, formation of cerebral spinal fluid, and the secretion of insulin. So, it is not surprising that deficient or overactive carbonic anhydrase enzymes can result in various pathologies:
Carbonic anhydrase (CA) II deficiency: CA II is found in many tissues throughout the body of mammals. Deficiency of this type of CA enzyme has been linked to the formation of overly dense bones, delayed development, bone fractures, short stature, calcification of the brain, intellectual disabilities, and a build-up of acids in the kidney.
CA 4 gene mutation: CA 4 is found in the eyes and mutations in this form of CA are linked with retinitis pigmentosa, a rare eye disease that can lead to problems seeing colors as well as a reduction or loss of vision.
CA VA deficiency: Deficiency of CA VA in the mitochondria of cells can lead to metabolic diseases because bicarbonate is important in several metabolic processes such as the production of glucose and fatty acids in cells. That means deficiency can lead to issues with glucose and fat regulation, high levels of ammonia, and acidosis resulting from overproduction of ketones.
CA 6 gene polymorphism: CA 6 is a salivary enzyme so mutations have been linked with risk (or not) of developing cavities and may be involved in taste perception.
CA 8 gene mutation: Interestingly, CA 8 is related to carbonic anhydrase but has no enzymatic properties. It has been identified in all vertebrates studied to date as well as some species of invertebrates. Mutations in this gene can lead to cognitive impairments and quadrupedal gait in humans.
CA 12 gene mutation: People with this mutation may have impaired ability to regulate sodium, potassium, and chloride balance in the body. Some may also develop symptoms similar to cystic fibrosis.
The future of carbonic anhydrase research is exciting because scientists are studying various inhibitors of these enzymes as potential treatments for a range of pathologies like glaucoma, cancer, epilepsy, acute mountain sickness, and brain edema.
A Aspatwar, MEE Tolvanen, H Barker, L Syrjanen, S Valanne, S Purmonen, A Waheed, WS Sly, S Parkkila. Carbonic anhydrases in metazoan model organisms: molecules, mechanisms, and physiology. Physiological Reviews. 103(3): 1327-1383, 2022.
Categories: Comparative Physiology, Illnesses and Injuries, Intelligence and Neuroscience
Tags: American Physiological Society, Carbonic anhydrase, gene mutation, genetic, pH, Physiological Reviews
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