Carbonic Anhydrases and Metabolism
Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated...
Na minha lista:
| Autor principal: | |
|---|---|
| Formato: | Online |
| Idioma: | inglês |
| Publicado em: |
MDPI - Multidisciplinary Digital Publishing Institute
2021
|
| Assuntos: | |
| Acesso em linha: | 33214 |
| Tags: |
Sem tags, seja o primeiro a adicionar uma tag!
|
| _version_ | 1869516918596042752 |
|---|---|
| author | Supuran, Claudiu T. |
| author_browse | Supuran, Claudiu T. |
| author_facet | Supuran, Claudiu T. |
| author_sort | Supuran, Claudiu T. |
| collection | Directory of Open Access Books |
| description | Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism. |
| format | Online |
| id | doab-20.500.12854ir-42706 |
| institution | Directory of Open Access Books |
| language | eng |
| publishDate | 2021 |
| publishDateRange | 2021 |
| publishDateSort | 2021 |
| publisher | MDPI - Multidisciplinary Digital Publishing Institute |
| publisherStr | MDPI - Multidisciplinary Digital Publishing Institute |
| record_format | ojs |
| spelling | doab-20.500.12854ir-427062024-04-05T12:32:01Z Carbonic Anhydrases and Metabolism Supuran, Claudiu T. QH301-705.5 Q1-390 antibiotic inhibitors glaucoma metabolic role inhibitor engineered bacteria carbonic anhydrase inhibitors drug discovery enzyme inhibition V-ATPases photosynthesis Chlamydomonas reinhardtii metalloenzymes CO2 capture bicarbonate benzamide hypoxia antibody model alga cancer therapeutics CA gene family resistance isoforms IX and XII cancer metabolism MMP14 carbonic anhydrase IX carboxylation bacterial enzymes antitumor agent metabolism activator bacterial carbonic anhydrases amine amino acid pH regulation proton pump inhibitors pathogens sulfonamide metastasis hypoxic tumor carbonic anhydrase pH carbonic anhydrases protozoan integrin Entamoeba histolytica tumors human isoform acidity invasion radiation tumor carbonic anhydrase XII transporter migration cancer tumor microenvironment thema EDItEUR::P Mathematics and Science::PS Biology, life sciences Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism. 2021-02-11T09:31:04Z 2021-02-11T09:31:04Z 2019-04-25 16:37:17 2019 book 33214 9783038978015 9783038978008 https://directory.doabooks.org/handle/20.500.12854/42706 eng image/jpeg Attribution-NonCommercial-NoDerivatives 4.0 International https://play.google.com/books/publish/a/14935057684283403269#details/ISBN:9783038978008 https://mdpi.com/books/pdfview/book/1215 MDPI - Multidisciplinary Digital Publishing Institute 10.3390/books978-3-03897-801-5 10.3390/books978-3-03897-801-5 46cabcaa-dd94-4bfe-87b4-55023c1b36d0 9783038978015 9783038978008 184 open access |
| spellingShingle | QH301-705.5 Q1-390 antibiotic inhibitors glaucoma metabolic role inhibitor engineered bacteria carbonic anhydrase inhibitors drug discovery enzyme inhibition V-ATPases photosynthesis Chlamydomonas reinhardtii metalloenzymes CO2 capture bicarbonate benzamide hypoxia antibody model alga cancer therapeutics CA gene family resistance isoforms IX and XII cancer metabolism MMP14 carbonic anhydrase IX carboxylation bacterial enzymes antitumor agent metabolism activator bacterial carbonic anhydrases amine amino acid pH regulation proton pump inhibitors pathogens sulfonamide metastasis hypoxic tumor carbonic anhydrase pH carbonic anhydrases protozoan integrin Entamoeba histolytica tumors human isoform acidity invasion radiation tumor carbonic anhydrase XII transporter migration cancer tumor microenvironment thema EDItEUR::P Mathematics and Science::PS Biology, life sciences Supuran, Claudiu T. Carbonic Anhydrases and Metabolism |
| title | Carbonic Anhydrases and Metabolism |
| title_full | Carbonic Anhydrases and Metabolism |
| title_fullStr | Carbonic Anhydrases and Metabolism |
| title_full_unstemmed | Carbonic Anhydrases and Metabolism |
| title_short | Carbonic Anhydrases and Metabolism |
| title_sort | carbonic anhydrases and metabolism |
| topic | QH301-705.5 Q1-390 antibiotic inhibitors glaucoma metabolic role inhibitor engineered bacteria carbonic anhydrase inhibitors drug discovery enzyme inhibition V-ATPases photosynthesis Chlamydomonas reinhardtii metalloenzymes CO2 capture bicarbonate benzamide hypoxia antibody model alga cancer therapeutics CA gene family resistance isoforms IX and XII cancer metabolism MMP14 carbonic anhydrase IX carboxylation bacterial enzymes antitumor agent metabolism activator bacterial carbonic anhydrases amine amino acid pH regulation proton pump inhibitors pathogens sulfonamide metastasis hypoxic tumor carbonic anhydrase pH carbonic anhydrases protozoan integrin Entamoeba histolytica tumors human isoform acidity invasion radiation tumor carbonic anhydrase XII transporter migration cancer tumor microenvironment thema EDItEUR::P Mathematics and Science::PS Biology, life sciences |
| topic_facet | QH301-705.5 Q1-390 antibiotic inhibitors glaucoma metabolic role inhibitor engineered bacteria carbonic anhydrase inhibitors drug discovery enzyme inhibition V-ATPases photosynthesis Chlamydomonas reinhardtii metalloenzymes CO2 capture bicarbonate benzamide hypoxia antibody model alga cancer therapeutics CA gene family resistance isoforms IX and XII cancer metabolism MMP14 carbonic anhydrase IX carboxylation bacterial enzymes antitumor agent metabolism activator bacterial carbonic anhydrases amine amino acid pH regulation proton pump inhibitors pathogens sulfonamide metastasis hypoxic tumor carbonic anhydrase pH carbonic anhydrases protozoan integrin Entamoeba histolytica tumors human isoform acidity invasion radiation tumor carbonic anhydrase XII transporter migration cancer tumor microenvironment thema EDItEUR::P Mathematics and Science::PS Biology, life sciences |
| url | 33214 |
| work_keys_str_mv | AT supuranclaudiut carbonicanhydrasesandmetabolism |