Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes in mammals, being involved in numerous biosynthetic processes, including gluconeogenesis, lipogenesis and ureagenesis. It has recently emerged that CA inhibitors (CAIs) targeting the mitochondrial isoforms CA VA and VB have potential as novel antiobesity drugs. This Editorial discusses the biochemical and biological rationale for the use of CAIs in the management of obesity. Obesity is one of the most common human diseases. However, there are few nontoxic pharmacological approaches for its treatment or prevention . Most drugs used for the management of obesity have serious cardiovascular or CNS side effects, which dramatically limit their usefulness. Recently, inhibition of carbonic anhydrases (CAs, EC 4.2.1.1) has been proposed as a new antiobesity strategy. Indeed, at least 15 different a-CA isoforms were so far described in vertebrates, where these zinc enzymes play crucial physiological roles. Five of them are cytosolic (CA I, CA II, CA III, CA VII and CA XIII), five others are membrane-associated (CA IV, CA IX, CA XII, CA XIV and CA XV) and CA VA and CA VB are mitochondrial and CA VI is secreted in saliva. Three acatalytic forms are also known, which were denominated CA-related proteins (CARP), CARP VIII, CARP X and CARP XI, as they lack one or two zinc ligands, which are crucial for the binding of the metal ion. Several important physiologic functions are played by the CA isozymes present in organisms all over the phylogenetic tree, related to respiration and transport of CO2/bicarbonate between metabolizing tissues and the lungs, pH and CO2 homeostasis, electrolyte secretion in a variety of tissues/organs, biosynthetic reactions, such as the lipogenesis, gluconeogenesis and ureagenesis among others (in animals), CO2 fixation (in plants and algae), virulence (in pathogenic bacteria/fungi) and so on. The presence of these ubiquitous enzymes in so many tissues and in so different forms represents an attractive goal for the design of inhibitors or activators with biomedical applications. Indeed, in addition to the use of the CA inhibitors (CAIs) as antiglaucoma agents, diuretics and anticonvulsants, CA IX and XII, isoforms predominantly found in cancerous tissues, were recently validated as antitumor targets, with several monoclonal antibodies and smallmolecule inhibitors in advanced clinical evaluations both for the imaging and for treatment of hypoxic solid tumors.
Submit manuscripts at https://www.scholarscentral.org/submissions/industrial-electronics-applications.html or an e-mail attachment to the Editorial Office at manuscripts@scitechnol.com
Best Regards,
Editorial Manager
Journal of Pharmaceutical Sciences & Emerging Drugs
Email: editor.jpsed@peerjournal.org