Carbonic Anhydrases and Metabolism

Front Cover
Claudiu T. Supuran
MDPI, Apr 8, 2019 - Science - 184 pages

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. 

 

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Contents

Common terms and phrases

Acad agents amino acid antibody anticancer antitumor bacteria bicarbonate Biochem Biol Bioorg breast cancer C.T. Carbonic anhydrase CA-IX CAH1 CAIs CAIX inhibitors Cancer Res cancer stem cells Capasso carbonic anhydrase inhibitors Carta catalytic activity characterization Chem Chlamydomonas reinhardtii clinical trials compounds CrossRef CrossRef][PubMed cytosolic derivatives domain effect EhiCA enzyme Enzyme Inhib Expert Opin expression extracellular Figure function growth HCO3 human carbonic anhydrase hydration hypoxia hypoxia-inducible hypoxic tumors inhibition integrin interaction invasion investigated isoforms isozymes lactate lansoprazole Lett mechanism melanoma membrane metabolic Metabolites metastasis metastatic mitochondrial moiety molecule Natl novel Oncol overexpression Parkkila Pastorek Pastorekova pathogenic pathways pH regulation Physiol potential PPIs protein Proton pump inhibitors PubMed radiation renal cell carcinoma residues role Scozzafava structure studies sulfonamides Supuran therapeutic therapy tissues transmembrane transporters tumor cell tumor microenvironment tumor-associated upregulation V-ATPase Vibrio cholerae vitro vivo Vullo Winum xenografts

About the author (2019)

Claudiu T. Supuran has been the Professor of Medicinal and Pharmaceutical Chemistry at the University of Florence, Italy, since 1995. He completed his PhD at the University of Bucharest, Romania, and was a visiting scholar at the University of Florida, Gainesville, USA, and at Griffith University, Brisbane, Australia. He was a visiting professor at the University of La Plata, Argentina, and at the University of New South Wales, Sydney, Australia. His main research interest is the medicinal chemistry/biochemistry of carbonic anhydrases, a field in which he has made contributions to the design of many novel classes of enzyme inhibitors and activators, deciphering their mechanism of action at the molecular level; the discovery of new isoforms and their role in disease (cancer, obesity, epilepsy, neuropathic pain, and cognition); and the discovery and characterization of carbonic anhydrases from various organisms (bacteria, fungi, corals, vertebrates other than humans and rodents, etc). Other research interests of his include the X-ray crystallography of metalloenzymes, biologically active organoelement derivatives, QSAR studies, metal-based drugs, cyclooxygenases, serine proteases, matrix metalloproteinases, bacterial proteases, amino acid derivatives, heterocyclic chemistry, and the chemistry of sulfonamides, sulfamates, and sulfamides, among others. He has published more than 1500 papers in these fields, and his Hirsch index is 134. One of the compounds discovered in his laboratory (SLC-0111) is in Phase II clinical trials for the treatment of advanced metastatic solid tumors. 

Bibliographic information

TitleCarbonic Anhydrases and Metabolism
EditorClaudiu T. Supuran
Editionillustrated
PublisherMDPI, 2019
ISBN3038978000, 9783038978008
Length184 pages
Subjects ›  › 

Science / Life Sciences / Molecular Biology
  
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