Abstract
Although the role of carbonic anhydrases (CAs, EC 4.2.1.1) in metabolism is well-established, pharmacological applications of this phenomenon started to be considered only recently. In organisms all over the phylogenetic tree, the seven CA genetic families known to date are involved in biosynthetic processes and pH modulation, which may influence metabolism in multiple ways, with both processes being amenable to pharmacologic intervention. CA inhibitors possess antiobesity action directly by inhibiting lipogenesis, whereas the hypoxic tumor metabolism is highly controlled by the transmembrane isoforms CA IX and XII, which contribute to the acidic extracellular environment of tumors and supply bicarbonate for their high proliferation rates. Many of the articles from this special issue deal with the role of cancer CAs in tumor metabolism and how these phenomena can be used for designing innovative antitumor therapies/imaging agents. The metabolic roles of CAs in bacteria and algae are also discussed.
Highlights
The role of carbonic anhydrases (CAs, EC 4.2.1.1) in metabolism is well-established, pharmacological applications of this phenomenon started to be considered only recently
Inhibition of the CAs has pharmacologic applications in many fields, such as diuretics [9], antiglaucoma [10], anticonvulsant [7,8,11], antiobesity [11], and anticancer agents/diagnostic tools [1,2,12], but it is emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action [4,5,8,17,18]
The metabolic reactions with which CA activity interference has been mostly studied include de novo glucogenesis, urea biosynthesis, and lipogenesis in animals [1,2,3,4,5,6,7,19,20] as well as the initial steps of the photosynthetic process in some bacteria, algae, and plants, due to the role that CAs have in providing bicarbonate to RUBISCO [22,23,26]
Summary
The role of carbonic anhydrases (CAs, EC 4.2.1.1) in metabolism is well-established, pharmacological applications of this phenomenon started to be considered only recently. The CAs may be considered as important checkpoint enzymes for relevant physiologic processes connected to a host of metabolic pathways, in all types of organisms, from bacteria and archaea [24,25] to algae, plants [26], and other eukaryotes (starting with the simple ones, yeasts and protozoa, and ending with the complex ones, including vertebrates) [1,2,3,4,5,6,7].
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