Journal ArticleDOI
Carbonic anhydrases--an overview.
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TLDR
Several important physiological and physio-pathological functions are played by CA isozymes present in organisms all over the phylogenetic tree, related to respiration and transport of CO(2)/bicarbonate between metabolizing tissues and the lungs, pH andCO(2) homeostasis, electrolyte secretion in a variety of tissues/organs, biosynthetic reactions, and more.Abstract:
Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread metalloenzymes all over the phylogenetic tree, with at least 4 distinct gene families encoding for them. At least 16 different alpha-CA isoforms were isolated in mammals, where these enzymes play crucial physiological roles. Representatives of the beta-delta-CA family are highly abundant in plants, diatoms, eubacteria and archaea. These enzymes are efficient catalysts for the reversible hydration of carbon dioxide to bicarbonate, but at least the alpha-CAs possess a high versatility, being able to catalyze different other hydrolytic processes The catalytic mechanism of the alpha-CAs is understood in detail: the active site consists of a Zn(II) ion co-ordinated by three histidine residues and a water molecule/hydroxide ion. The latter is the active species, acting as a potent nucleophile. For beta- and gamma-CAs, the zinc hydroxide mechanism is valid too, although at least some beta-class enzymes do not have water directly coordinated to the metal ion. CAs are inhibited by two classes of compounds: the metal complexing anions and the sulfonamides and their isosteres (sulfamates, sulfamides etc.) possessing the general formula RXSO(2)NH(2) (R = aryl; hetaryl; perhaloalkyl; X = nothing, O or NH). At least 25 clinically used drugs/agents in clinical development show applications as diuretics and antiglaucoma drugs, anticonvulsants, with some compounds being developed as anticancer agents/diagnostic tools for tumors, antiobesity agents, and antimicrobials/antifungals (inhibitors targeting CAs from pathogenic organisms such as Helicobacter pylori, Mycobacterium tuberculosis, Plasmodium falciparum, Candida albicans, etc). Several important physiological and physio-pathological functions are played by CA isozymes present in organisms all over the phylogenetic tree, related to respiration and transport of CO(2)/bicarbonate between metabolizing tissues and the lungs, pH and CO(2) homeostasis, electrolyte secretion in a variety of tissues/organs, biosynthetic reactions, such as the gluconeogenesis and ureagenesis among others (in animals), CO(2) fixation (in plants and algae), etc. The presence of these ubiquitous enzymes in so many tissues and in so different isoforms, represents an attractive goal for the design of inhibitors or activators with biomedical applications.read more
Citations
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Physiological functions of mineral micronutrients (Cu, Zn, Mn, Fe, Ni, Mo, B, Cl).
Robert Hänsch,Ralf R. Mendel +1 more
TL;DR: This review focuses on the major functions of mineral micronutrients, mostly in cases where they were shown as constituents of proteins, making a selection and highlighting some functions in more detail.
Journal ArticleDOI
The taste of carbonation.
Jayaram Chandrashekar,David A. Yarmolinsky,Lars J. von Buchholtz,Yuki Oka,William S. Sly,Nicholas J. P. Ryba,Charles S. Zuker +6 more
TL;DR: It is demonstrated that the sour-sensing cells act as the taste sensors for carbonation, and showed that carbonic anhydrase 4, a glycosylphosphatidylinositol-anchored enzyme, functions as the principal CO2 taste sensor.
Journal ArticleDOI
An overview of the alpha-, beta- and gamma-carbonic anhydrases from Bacteria: can bacterial carbonic anhydrases shed new light on evolution of bacteria?
TL;DR: It is proposed that bacterial CAs can be used as markers for understanding the evolution and genetic variability of the Gram-positive and Gram-negative bacteria.
Journal ArticleDOI
Whole Transcriptome Analysis of the Coral Acropora millepora Reveals Complex Responses to CO2-driven Acidification during the Initiation of Calcification
Aurelie Moya,L. Huisman,L. Huisman,Eldon E. Ball,David C. Hayward,Lauretta C. Grasso,Lauretta C. Grasso,Chia-Miin Chua,H.N. Woo,Jean-Pierre Gattuso,Jean-Pierre Gattuso,Sylvain Forêt,David J. Miller +12 more
TL;DR: This study is the first exhaustive exploration of the transcriptomic response of a scleractinian coral to acidification and provides an unbiased perspective on its effects during the early stages of calcification.
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Dental enamel formation and implications for oral health and disease.
Rodrigo S. Lacruz,Stefan Habelitz,J. Timothy Wright,J. Timothy Wright,J. Timothy Wright,Michael L. Paine +5 more
TL;DR: Key aspects of dental enamel formation are examined, from its developmental genesis to the ever-increasing wealth of data on the mechanisms mediating ionic transport, as well as the clinical outcomes resulting from abnormal ameloblast function.
References
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Journal ArticleDOI
Carbonic anhydrases: novel therapeutic applications for inhibitors and activators
TL;DR: The biological rationale for the novel uses of inhibitors or activators of CA activity in multiple diseases is discussed, and progress in the development of specific modulators of the relevant CA isoforms is highlighted, some of which are now being evaluated in clinical trials.
PatentDOI
Carbonic anhydrase inhibitors
Peter Ebbesen,Claudlu T. Supuran,Andrea Scozzafava,Erik Olai Pettersen,Kaye Williams,L.J. Dubois,Philippe Lambin +6 more
TL;DR: A carbonic anhydrase IX (CA IX) inhibitor is a compound of general formula: R-NH-CX-NH-(CH 2 ) n -Ar-Q-SO 2 -NH 2 or a pharmaceutically acceptable salt, derivative or prodrug thereof.
Journal ArticleDOI
Carbonic anhydrase inhibitors
TL;DR: This class of enzyme inhibitors shows promise for designing interesting pharmacological agents and understanding in detail protein-drug interactions at molecular level.
Patent
Carbonic anhydrase inhibitors
TL;DR: In this paper, the compounds of the following formula are disclosed: Compounds of Formula I are the topic of this invention: wherein G, J and the two atoms of the thiophene ring to which they are attached form a six-membered ring chosen from
Journal ArticleDOI
Carbonic anhydrases as targets for medicinal chemistry
TL;DR: Several important physiological and physio-pathological functions are played by CAs present in organisms all over the phylogenetic tree, related to respiration and transport of carbon dioxide to bicarbonate between metabolizing tissues and the lungs, pH and CO(2) homeostasis, electrolyte secretion in a variety of tissues/organs, biosynthetic reactions, such as the gluconeogenesis and ureagenesis among others.