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Basic research on enzymes leads to several treatment options

Published on 23.2.2022
Tampere University
viitekuvassa hiilihappoanhydraasitutkimuksen elementtejä
Long-term basic research on carbonic anhydrases has begun to produce clinical applications that are useful in the treatment of patients. According to a recent review article, using drugs to inhibit the enzyme activity of carbonic anhydrases is a promising treatment in a wide range of diseases.

“Over the past couple of decades, this area of research has been marked by the discovery of numerous new forms of enzymes,” says the lead author, Professor Seppo Parkkila from Tampere University.

“Only one family of carbonic anhydrases, known as alpha forms, is found in humans, while seven other enzyme families are found in varying degrees in other species, including insects, bacteria, fungi, and diatoms.

The review article Carbonic anhydrases in metazoan model organisms: molecules, mechanisms, and physiology, written by Parkkila and his research group, discusses the different isozymes of carbonic anhydrases and their physiological significance.

The article was published in the prestigious Physiological Reviews journal. Physiological Reviews publishes articles by invitation only and is considered the most respected journal in the field of physiology in the world.

Carbonic anhydrases are involved in many important physiological roles in the body. Their basic function is to catalyse the chemical reaction between carbon dioxide and water to produce carbonic acid, which in turn forms bicarbonate and hydrogen ions. Thus, carbonic anhydrases play a key role in regulating the acid-base homeostasis of cells and tissues.

Carbonic anhydrases are involved in the formation and pH regulation of a variety of biological fluids, such as the cerebrospinal fluid, gastric fluid, and pancreatic fluid. They also play a role in the spread of cancer cells at tissue level.

The review, which was published in Physiological Reviews, extensively discusses the symptoms that people develop because of mutations in their carbonic anhydrase genes. These results were compared with those obtained in experimental animals such as mice, zebrafish, Drosophila flies and nematodes.

The genetic deficiencies of carbonic anhydrases in humans can lead to, among other things, developmental disorders, vascular calcification, osteopetrosis and disturbances in the body’s acid-base homeostasis.

The article also discusses chemical compounds that have been developed in recent years to inhibit the activity of carbonic anhydrases.

“Several such inhibitors are in clinical use in the treatment of, among other things, epilepsy, mountain sickness, elevated intracranial pressure and glaucoma. Inhibitors currently in clinical trials are being developed for the treatment of cancer,” says Parkkila.

The article was authored by the following researchers at Tampere University: Dr. Ashok Aspatwar, Doctoral Researcher Harlan Barker, Dr. Leo Syrjänen, University Lecturer Susanna Valanne, University Instructor Sami Purmonen and Professor Seppo Parkkila. University Lecturer Martti Tolvanen from the University of Turku also worked on the article as did Professors Abdul Waheed and William S. Sly from the Saint Louis University in the US.

Research on carbonic anhydrases has a decades-long history in Finland. The pioneer of Finnish research in this field is Professor L. Kalevi Korhonen, who worked at the Universities of Turku and Oulu and published the first histochemical evidence of carbonic anhydrase activity in the uterus as early as 1966. Professor Parkkila continued this line of research in the 1980s and 1990s at the University of Oulu, in the 1990s in the United States and, since 2002, at Tampere University.

“The fact that Physiological Reviews asked us for a review article is the result of long-term basic research. Decades of scientific research on carbonic anhydrases are producing clinical applications that are also useful in the treatment of patients,” Parkkila says.

The citation impact factor of Physiological Reviews is 37.3 and it only accepts about 40 articles each year.

Aspatwar A., Barker H., Syrjänen L., Valanne S., Purmonen S., Tolvanen M., Abdul Waheed A., Sly W.S., Parkkila S.: Carbonic anhydrases in metazoan model organisms: molecules, mechanisms, and physiology
https://doi.org/10.1152/physrev.00018.2021

 
Photograph: Jukka Lehtiniemi/Jonne Renvall