Carbonic Anhydrases: A family of zinc-containing enzymes that catalyze the reversible hydration of carbon dioxide. They play an important role in the transport of CARBON DIOXIDE from the tissues to the LUNG. EC 4.2.1.1.Carbonic Anhydrase IV: A membrane-bound carbonic anhydrase found in lung capillaries and kidney.Carbonic Anhydrase II: A cytosolic carbonic anhydrase isoenzyme found widely distributed in cells of almost all tissues. Deficiencies of carbonic anhydrase II produce a syndrome characterized by OSTEOPETROSIS, renal tubular acidosis (ACIDOSIS, RENAL TUBULAR) and cerebral calcification. EC 4.2.1.-Carbonic Anhydrase I: A cytosolic carbonic anhydrase isoenzyme primarily expressed in ERYTHROCYTES, vascular endothelial cells, and the gastrointestinal mucosa. EC 4.2.1.-Carbonic Anhydrase Inhibitors: A class of compounds that reduces the secretion of H+ ions by the proximal kidney tubule through inhibition of CARBONIC ANHYDRASES.Carbonic Anhydrase V: A carbonic anhydrase isoenzyme found in MITOCHONDRIA where it provides bicarbonate ions that are components in the urea cycle and in GLUCONEOGENESIS.Bicarbonates: Inorganic salts that contain the -HCO3 radical. They are an important factor in determining the pH of the blood and the concentration of bicarbonate ions is regulated by the kidney. Levels in the blood are an index of the alkali reserve or buffering capacity.Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals.Hydrogen-Ion Concentration: The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)Acetazolamide: One of the CARBONIC ANHYDRASE INHIBITORS that is sometimes effective against absence seizures. It is sometimes useful also as an adjunct in the treatment of tonic-clonic, myoclonic, and atonic seizures, particularly in women whose seizures occur or are exacerbated at specific times in the menstrual cycle. However, its usefulness is transient often because of rapid development of tolerance. Its antiepileptic effect may be due to its inhibitory effect on brain carbonic anhydrase, which leads to an increased transneuronal chloride gradient, increased chloride current, and increased inhibition. (From Smith and Reynard, Textbook of Pharmacology, 1991, p337)Zinc: A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Sordariales: An order of fungi in the phylum ASCOMYCOTA that includes many valuable experimental organisms. There are eight families and very few anamorphic forms.Fruiting Bodies, Fungal: The fruiting 'heads' or 'caps' of FUNGI, which as a food item are familiarly known as MUSHROOMS, that contain the FUNGAL SPORES.Sulfonamides: A group of compounds that contain the structure SO2NH2.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Kinetics: The rate dynamics in chemical or physical systems.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Carcinoma, Renal Cell: A heterogeneous group of sporadic or hereditary carcinoma derived from cells of the KIDNEYS. There are several subtypes including the clear cells, the papillary, the chromophobe, the collecting duct, the spindle cells (sarcomatoid), or mixed cell-type carcinoma.Encyclopedias as Topic: Works containing information articles on subjects in every field of knowledge, usually arranged in alphabetical order, or a similar work limited to a special field or subject. (From The ALA Glossary of Library and Information Science, 1983)Kidney Neoplasms: Tumors or cancers of the KIDNEY.Von Hippel-Lindau Tumor Suppressor Protein: A ubiquitin-protein ligase that mediates OXYGEN-dependent polyubiquitination of HYPOXIA-INDUCIBLE FACTOR 1, ALPHA SUBUNIT. It is inactivated in VON HIPPEL-LINDAU SYNDROME.PubMed: A bibliographic database that includes MEDLINE as its primary subset. It is produced by the National Center for Biotechnology Information (NCBI), part of the NATIONAL LIBRARY OF MEDICINE. PubMed, which is searchable through NLM's Web site, also includes access to additional citations to selected life sciences journals not in MEDLINE, and links to other resources such as the full-text of articles at participating publishers' Web sites, NCBI's molecular biology databases, and PubMed Central.Periodicals as Topic: A publication issued at stated, more or less regular, intervals.Methazolamide: A carbonic anhydrase inhibitor that is used as a diuretic and in the treatment of glaucoma.Dichlorphenamide: A carbonic anhydrase inhibitor that is used in the treatment of glaucoma.Ethoxzolamide: A carbonic anhydrase inhibitor used as diuretic and in glaucoma. It may cause hypokalemia.Benzolamide: Selective renal carbonic anhydrase inhibitor. It may also be of use in certain cases of respiratory failure.Nitrosomonas: A genus of gram-negative, ellipsoidal or rod-shaped bacteria whose major source of energy and reducing power is from the oxidation of ammonia to nitrite. Its species occur in soils, oceans, lakes, rivers, and sewage disposal systems.Nitrosomonas europaea: The type species of the genus NITROSOMONAS, a gram-negative chemolithotroph that oxidizes ammonia to nitrite. It is found in soil, sewage, freshwater, and on building walls, and especially in polluted areas where air contains high levels of nitrogen compounds.Sodium Bicarbonate: A white, crystalline powder that is commonly used as a pH buffering agent, an electrolyte replenisher, systemic alkalizer and in topical cleansing solutions.Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.Carbonic Anhydrase III: A cytosolic carbonic anhydrase isoenzyme primarily expressed in skeletal muscle (MUSCLES, SKELETAL). EC 4.2.1.-Salicylic Acid: A compound obtained from the bark of the white willow and wintergreen leaves. It has bacteriostatic, fungicidal, and keratolytic actions.Arabidopsis Proteins: Proteins that originate from plants species belonging to the genus ARABIDOPSIS. The most intensely studied species of Arabidopsis, Arabidopsis thaliana, is commonly used in laboratory experiments.Arabidopsis: A plant genus of the family BRASSICACEAE that contains ARABIDOPSIS PROTEINS and MADS DOMAIN PROTEINS. The species A. thaliana is used for experiments in classical plant genetics as well as molecular genetic studies in plant physiology, biochemistry, and development.Octamer Transcription Factors: A family of POU domain factors that bind the octamer motif ATTTGCAT in enhancer and PROMOTER REGIONS to regulate GENE EXPRESSION.Factor IX: Storage-stable blood coagulation factor acting in the intrinsic pathway. Its activated form, IXa, forms a complex with factor VIII and calcium on platelet factor 3 to activate factor X to Xa. Deficiency of factor IX results in HEMOPHILIA B (Christmas Disease).Hemophilia B: A deficiency of blood coagulation factor IX inherited as an X-linked disorder. (Also known as Christmas Disease, after the first patient studied in detail, not the holy day.) Historical and clinical features resemble those in classic hemophilia (HEMOPHILIA A), but patients present with fewer symptoms. Severity of bleeding is usually similar in members of a single family. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. Treatment is similar to that for hemophilia A. (From Cecil Textbook of Medicine, 19th ed, p1008)Antigens, Neoplasm: Proteins, glycoprotein, or lipoprotein moieties on surfaces of tumor cells that are usually identified by monoclonal antibodies. Many of these are of either embryonic or viral origin.Thermodynamics: A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)Psychrobacter: A genus of gram-negative, aerobic bacteria in the family MORAXELLACEAE, associated with processed MEAT; FISH PRODUCTS; and POULTRY PRODUCTS.Antarctic Regions: The continent lying around the South Pole and the southern waters of the Atlantic, Pacific, and Indian Oceans. It includes the Falkland Islands Dependencies. (From Webster's New Geographical Dictionary, 1988, p55)Urease: An enzyme that catalyzes the conversion of urea and water to carbon dioxide and ammonia. EC 3.5.1.5.Calcium Carbonate: Carbonic acid calcium salt (CaCO3). An odorless, tasteless powder or crystal that occurs in nature. It is used therapeutically as a phosphate buffer in hemodialysis patients and as a calcium supplement.Hyperventilation: A pulmonary ventilation rate faster than is metabolically necessary for the exchange of gases. It is the result of an increased frequency of breathing, an increased tidal volume, or a combination of both. It causes an excess intake of oxygen and the blowing off of carbon dioxide.Boredom: A psychological state resulting from any activity that lacks motivation, or from enforced continuance in an uninteresting situation.

Does gill boundary layer carbonic anhydrase contribute to carbon dioxide excretion: a comparison between dogfish (Squalus acanthias) and rainbow trout (Oncorhynchus mykiss). (1/1306)

In vivo experiments were conducted on spiny dogfish (Squalus acanthias) and rainbow trout (Oncorhynchus mykiss) in sea water to determine the potential role of externally oriented or gill boundary layer carbonic anhydrase in carbon dioxide excretion. This was accomplished by assessing pH changes in expired water using a stopped-flow apparatus. In dogfish, expired water was in acid-base disequilibrium as indicated by a pronounced acidification (delta pH=-0.11+/-0.01; N=22; mean +/- s.e.m.) during the period of stopped flow; inspired water, however, was in acid-base equilibrium (delta pH=-0.002+/-0.01; N=22). The acid-base disequilibrium in expired water was abolished (delta pH=-0.005+/-0.01; N=6) by the addition of bovine carbonic anhydrase (5 mg l-1) to the external medium. Addition of the carbonic anhydrase inhibitor acetazolamide (1 mmol l-1) to the water significantly reduced the magnitude of the pH disequilibrium (from -0.133+/-0.03 to -0.063+/-0.02; N=4). However, after correcting for the increased buffering capacity of the water caused by acetazolamide, the acid-base disequilibrium during stopped flow was unaffected by this treatment (control delta [H+]=99.8+/-22.8 micromol l-1; acetazolamide delta [H+]=81.3+/-21.5 micromol l-1). In rainbow trout, expired water displayed an acid-base disequilibrium (delta pH=0.09+/-0.01; N=6) that also was abolished by the application of external carbonic anhydrase (delta pH=0.02+/-0.01). The origin of the expired water acid-base disequilibrium was investigated further in dogfish. Intravascular injection of acetazolamide (40 mg kg-1) to inhibit internal carbonic anhydrase activity non-specifically and thus CO2 excretion significantly diminished the extent of the expired water disequilibrium pH after 30 min (from -0.123+/-0.01 to -0.065+/-0.01; N=6). Selective inhibition of extracellular carbonic anhydrase activity using a low intravascular dose (1.3 mg kg-1) of the inhibitor benzolamide caused a significant reduction in the acid-base disequilibrium after 5 min (from -0.11+/-0.01 to -0.07+/-0. 01; N=14). These results demonstrate that the expired water acid-base disequilibrium originates, at least in part, from excretory CO2 and that extracellular carbonic anhydrase in dogfish may have a significant role in carbon dioxide excretion. However, externally oriented carbonic anhydrase (if present in dogfish) plays no role in catalysing the hydration of the excretory CO2 in water flowing over the gills and thus is unlikely to facilitate CO2 excretion.  (+info)

Role of a novel photosystem II-associated carbonic anhydrase in photosynthetic carbon assimilation in Chlamydomonas reinhardtii. (2/1306)

Intracellular carbonic anhydrases (CA) in aquatic photosynthetic organisms are involved in the CO2-concentrating mechanism (CCM), which helps to overcome CO2 limitation in the environment. In the green alga Chlamydomonas reinhardtii, this CCM is initiated and maintained by the pH gradient created across the chloroplast thylakoid membranes by photosystem (PS) II-mediated electron transport. We show here that photosynthesis is stimulated by a novel, intracellular alpha-CA bound to the chloroplast thylakoids. It is associated with PSII on the lumenal side of the thylakoid membranes. We demonstrate that PSII in association with this lumenal CA operates to provide an ample flux of CO2 for carboxylation.  (+info)

Modulation of chloride, potassium and bicarbonate transport by muscarinic receptors in a human adenocarcinoma cell line. (3/1306)

1. Short-circuit current (I(SC)) responses to carbachol (CCh) were investigated in Colony 1 epithelia, a subpopulation of the HCA-7 adenocarcinoma cell line. In Krebs-Henseleit (KH) buffer, CCh responses consisted of three I(SC) components: an unusual rapid decrease (the 10 s spike) followed by an upward spike at 30 s and a slower transient increase (the 2 min peak). This response was not potentiated by forskolin; rather, CCh inhibited cyclic AMP-stimulated I(SC). 2. In HCO3- free buffer, the decrease in forskolin-elevated I(SC) after CCh was reduced, although the interactions between CCh and forskolin remained at best additive rather than synergistic. When Cl- anions were replaced by gluconate, both Ca2+- and cyclic AMP-mediated electrogenic responses were significantly inhibited. 3. Basolateral Ba2+ (1-10 mM) and 293B (10 microM) selectively inhibited forskolin stimulation of I(SC), without altering the effects of CCh. Under Ba2+- or 293B-treated conditions, CCh responses were potentiated by pretreatment with forskolin. 4. Basolateral charybdotoxin (50 nM) significantly increased the size of the 10 s spike of CCh responses in both KH and HCO3- free medium, without affecting the 2 min peak. The enhanced 10 s spike was inhibited by prior addition of 5 mM apical Ba2+. Charybdotoxin did not affect forskolin responses. 5. In epithelial layers prestimulated with forskolin, the muscarinic antagonists atropine and 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP, both at 100 nM) abolished subsequent 10 microM CCh responses. Following addition of p-fluoro hexahydro-sila-difenidol (pF-HHSiD, 10 microM) or pirenzepine (1 microM), qualitative changes in the CCh response time-profile also indicated a rightward shift of the agonist concentration-response curve; however, 1 microM gallamine had no effect. These results suggest that a single M3-like receptor subtype mediates the secretory response to CCh. 6. It is concluded that CCh and forskolin activate discrete populations of basolateral K+ channels gated by either Ca2+ or cyclic AMP, but that the Cl- permeability of the apical membrane may limit their combined effects on electrogenic Cl- secretion. In addition, CCh activates a Ba2+-sensitive apical K+ conductance leading to electrogenic K+ transport. Both agents may also modulate HCO3- secretion through a mechanism at least partially dependent on carbonic anhydrase.  (+info)

Carbonic anhydrase III protects cells from hydrogen peroxide-induced apoptosis. (4/1306)

Carbonic anhydrase III (CA III; EC 4.2.1.1) is a cytoplasmic enzyme that exhibits a relatively low carbon dioxide hydratase activity. It is expressed at a very high level in skeletal muscle, where physical exercise has been shown to increase free radical production. In this work we show the effect of overexpression of CA III on cellular response to oxidative stress. Rat CA III cDNA was transfected to NIH/3T3 cells, which have no endogenous CA III expression. The isolated clones expressed CA III mRNA and protein. The protein was localized to cytoplasm and nuclei. Compared to parental cells, transfected cells showed lower basal oxidized state as judged by measurement of intracellular reactive oxygen species (ROS) using fluorescent dye and an image analysis system. Addition of exogenous H2O2 to cells induced a rapid increase of ROS in control but not in CA III overexpressing cells. Association of this phenomenon with CA III expression was further confirmed by showing that overexpression of CA II could not prevent H2O2-stimulated increase of ROS. In proliferation assays, CA III overexpressing cells grew faster and were more resistant to cytotoxic concentrations of H2O2 than control cells. After a 16 h exposure to oxidative stress, the number of apoptotic cells was also reduced in transfectants. Our results suggest that CA III functions as an oxyradical scavenger and thus protects cells from oxidative damage. A lower level of free radicals in CA III overexpressing cells may also affect growth signaling pathways.  (+info)

A novel role for carbonic anhydrase: cytoplasmic pH gradient dissipation in mouse small intestinal enterocytes. (5/1306)

1. The spatial and temporal distribution of intracellular H+ ions in response to activation of a proton-coupled dipeptide transporter localized at the apical pole of mouse small intestinal isolated enterocytes was investigated using intracellular carboxy-SNARF-1 fluorescence in combination with whole-cell microspectrofluorimetry or confocal microscopy. 2. In Hepes-buffered Tyrode solution, application of the dipeptide Phe-Ala (10 mM) to a single enterocyte reduced pHi locally in the apical submembranous space. After a short delay (8 s), a fall of pHi occurred more slowly at the basal pole. 3. In the presence of CO2/HCO3--buffered Tyrode solution, the apical and basal rates of acidification were not significantly different and the time delay was reduced to 1 s or less. 4. Following application of the carbonic anhydrase inhibitor acetazolamide (100 microM) in the presence of CO2/HCO3- buffer, addition of Phe-Ala once again produced a localized apical acidification that took 5 s to reach the basal pole. Basal acidification was slower than at the apical pole. 5. We conclude that acid influx due to proton-coupled dipeptide transport can lead to intracellular pH gradients and that intracellular carbonic anhydrase activity, by facilitating cytoplasmic H+ mobility, limits their magnitude and duration.  (+info)

Characterization of a molten globule state of bovine carbonic anhydrase III: loss of asymmetrical environment of the aromatic residues has a profound effect on both the near- and far-UV CD spectrum. (6/1306)

Bovine muscle carbonic anhydrase (isoenzyme III; BCAIII) exhibited a three-state unfolding process at equilibrium upon denaturation in guanidine hydrochloride (GuHCl). The stable folding intermediate appeared to be of molten globule type. The stability towards GuHCl in terms of mid-point concentrations of denaturation were very similar for BCAIII and human CAII (HCAII). It was further demonstrated that the aromatic amino acid residues contributed significantly to the circular dichroism (CD) spectrum in the far-UV wavelength region during the native-->molten globule state transition. Thus, the ellipiticity change at 218 nm was shown to monitor the loss of tertiary interactions of aromatic side chains at the first unfolding transition as well as the rupture of secondary structure at the second unfolding transition. Similar aromatic contributions to the far-UV CD spectrum, but with varying magnitudes, were also noted for BCAII and HCAII, further emphasizing that interference of aromatic residues should not be neglected at wavelengths that normally are assigned to secondary structural changes.  (+info)

Denatured states of human carbonic anhydrase II: an NMR study of hydrogen/deuterium exchange at tryptophan-indole-H(N) sites. (7/1306)

Hydrogen/deuterium (H/D) exchange measurements in low and moderate concentrations of GuHCI were conducted on the side chain H(N) atoms of the seven tryptophans of pseudo wild-type human carbonic anhydrase II. Tryptophans 5, 16 and 245, situated in or close to the N-terminal domain were found to have little protection against exchange. The H/D exchange results for Trp-123, Trp-192 and Trp-209 showed that a previously identified molten globule and the native state gave a similar protection against exchange. Global unfolding of the protein is necessary for the efficient exchange at Trp-97, which is located in the central part of the beta-sheet.  (+info)

Detection of intermediates in protein folding of carbonic anhydrase with fluorescence emission and polarization. (8/1306)

The three-dimensional structure of carbonic anhydrase is a result of specific folding of the protein chain to form a compact, globular molecule. Fluorescence measurements on the nature of the rate-limiting steps in folding from the random coil to the native structure show that each step involves an actual folding reaction of the protein chain. Emission intensity and polarization of the intrinsic fluorescence due to tryptophan residues reach a maximum during the early period of the folding process. The changes occur in at least three kinetic phases (tau1 less than 3 S, tau2 = 1 min, tau3 = 10 min, 1 M guanidinium chloride, 2 M NaC1, pH 7, 20 degrees C). None of these phases are explained by configurational changes in the fully unfolded chain. The results are consistent with a kinetic scheme that involves stepwise acquisition of the specific folded structure of the native enzyme.  (+info)

Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related to α-carbonic anhydrases (α-CAs). These CARPs are found in animals (both vertebrates and invertebrates) and viruses as either independent proteins or domains of other proteins. We report here the identification of a new CARP (TgCA_RP) in the unicellular organism Toxoplasma gondii that is related to the recently described η-class CA found in Plasmodium falciparum. TgCA_RP is posttranslationally modified at its C terminus with a glycosylphosphatidylinositol anchor that is important for its localization in intracellular tachyzoites. The protein localizes throughout the rhoptry bulbs of mature tachyzoites and to the outer membrane of nascent rhoptries in dividing tachyzoites, as demonstrated by immunofluorescence and immunoelectron microscopy using specific antibodies. T. gondii mutant tachyzoites lacking TgCA_RP display a growth and invasion phenotype in vitro and have ...
TY - JOUR. T1 - Carbonic anhydrase IX expression in renal neoplasms. T2 - Correlation with tumor type and grade. AU - Genega, Elizabeth M.. AU - Ghebremichael, Musie. AU - Najarian, Robert. AU - Fu, Yineng. AU - Wang, Yihong. AU - Argani, Pedram. AU - Grisanzio, Chiara. AU - Signoretti, Sabina. PY - 2010/12. Y1 - 2010/12. N2 - Carbonic anhydrase IX (CAIX), a hypoxia-induced protein, is expressed in some renal tumors. We evaluated its immunohistochemical expression in 317 primary and 42 metastatic renal neoplasms (186 clear cell, 52 papillary, 35 chromophobe, 47 unclassified, and 15 Xp11.2 translocation renal cell carcinomas [RCCs]; 26 oncocytomas; 2 metanephric adenomas; 1 urothelial carcinoma; 1 mixed epithelial and stromal tumor; and 1 angiomyolipoma); 7 neoplasms were unknown as to whether they were primary or metastatic. We also correlated expression with tumor type and grade. Variable staining was seen in clear cell, papillary, unclassified, and Xp11.2 translocation carcinomas. One ...
Carbonic anhydrases are abundant in mammalian tissues, plants and bacteria. The several distinct classes of this enzyme (α, β, γ etc.) share little similarity in terms of structure and sequence, but they all perform the same function of catalyzing the hydration of carbon dioxide and the dehydration of bicarbonate [3]. Carbonic anhydrase B is one of the two major forms of carbonic anhydrase in human red blood cell (the other form is CA C). Like other members of the CA family, its main function is assisting the important chemical reaction that occurs in the blood. CO2 + H2O ,-----, HCO3- + H+. The above reaction is very slow in the absence of the enzyme. Hence, by assisting the inter-conversion between carbon dioxide and bicarbonate, Carbonic anhydrase B helps to maintain acid-base balance in blood, and transport carbon dioxide out of blood. Note that the carbonic acid (H2CO3) and hydrogen carbonate ions (HCO3-) is an important buffer system in the body. They equilibrate in the blood plasma to ...
Carbonic anhydrase IX (CAIX) is generally expressed in individual tumors and serves as a marker for hypoxia. Breasts. Am.J.Pathol. 2001;158:1011C1019. [PMC free of charge content] [PubMed] [10] Sowter HM, Raval R, Moore J, Ratcliffe PJ, Harris AL. Predominant Function of Hypoxia-Inducible Transcription Aspect Ednra (Hif)-1 Hif-2 in Legislation from the Transcriptional Response to Hypoxia. Cancers Res. 2003;63:6130C6134. [PubMed] [11] Chiche J, Ilc K, Laferriere J, Trottier E, Dayan F, Mazure NM, Brahimi-Horn MC, Pouyssegur J. Cyclopamine Hypoxia-Inducible Carbonic Anhydrase XII and IX Promote Tumor Cell Growth by Counteracting Acidosis coming from the Regulation from the Intracellular pH. Cancer tumor Res. 2009;69:358C368. [PubMed] [12] Swinson DEB, Jones JL, Richardson D, Wykoff C, Turley H, Pastorek J, Taub N, Harris AL, OBryne KJ. Carbonic Anhydrase IX Appearance, a Book Surrogate Marker of Tumor Hypoxia, Is normally Associated with an unhealthy Prognosis in Non-Small-Cell Lung Cancers. ...
The time course of and the influence of light intensity and light quality on the induction of a mitochondrial carbonic anhydrase (CA) in the unicellular green alga Chlamydomonas reinhardtii was characterized using western and northern blots. This CA was expressed only under low-CO2 conditions (ambient air). In asynchronously grown cells, the mRNA was detected 15 min after transfer from air containing 5% CO2 to ambient air, and the 21-kD polypeptide was detected on western blots after 1 h. When transferred back to air containing 5% CO2, the mRNA disappeared within 1 h and the polypeptide was degraded within 3 d. Photosynthesis was required for the induction in asynchronous cultures. The induction increased with light up to 500 mu mol m(-2) s(-1), where saturation occurred. In cells grown synchronously, however, expression of the mitochondrial CA was also detected in darkness. Under such conditions the expression followed a circadian rhythm, with mRNA appearing in the dark 30 min before the light ...
Carbonic anhydrase III (CAIII) is a member of a multigene family (at least six separate genes are known) that encodes carbonic anhydrase isozymes. These carbonic anhydrases are a class of metalloenzymes that catalyze the reversible hydration of carbon dioxide and are differentially expressed in a number of cell types. The expression of the CA3 gene is strictly tissue specific and present at high levels in skeletal muscle and much lower levels in cardiac and smooth muscle. A proportion of carriers of Duchenne muscle dystrophy have a higher CA3 level than normal. The gene spans 10.3 kb and contains seven exons and six introns. [provided by RefSeq, Oct 2008 ...
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PURPOSE: Bevacizumab, an anti-VEGFA antibody, inhibits the developing vasculature of tumors, but resistance is common. Antiangiogenic therapy induces hypoxia and we observed increased expression of hypoxia-regulated genes, including carbonic anhydrase IX (CAIX), in response to bevacizumab treatment in xenografts. CAIX expression correlates with poor prognosis in most tumor types and with worse outcome in bevacizumab-treated patients with metastatic colorectal cancer, malignant astrocytoma, and recurrent malignant glioma. EXPERIMENTAL DESIGN: We knocked down CAIX expression by short hairpin RNA in a colon cancer (HT29) and a glioblastoma (U87) cell line which have high hypoxic induction of CAIX and overexpressed CAIX in HCT116 cells which has low CAIX. We investigated the effect on growth rate in three-dimensional (3D) culture and in vivo, and examined the effect of CAIX knockdown in combination with bevacizumab. RESULTS: CAIX expression was associated with increased growth rate in spheroids and in vivo.
Zn(2+)-dependent carbonic anhydrases (CA) catalyse the reversible hydration of carbon dioxide to bicarbonate and participate in diverse physiological processes, hence having manifold therapeutic potentials. Among the 15 human CAs with wide-ranging sub-cellular localisation and kinetic properties, CA VI is the only secretory isoform. The 1.9Å crystal structure of the human CA VI catalytic domain reveals a prototypical mammalian CA fold, and a novel dimeric arrangement as compared to previously-reported CA structures. The active site cavity contains a cluster of non-conserved residues that may be involved in ligand binding and have significant implications for developing the next-generation of isoform-specific inhibitors.
The IUPHAR/BPS Guide to Pharmacology. carbonic anhydrase 9 - Carbonic anhydrases. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
The transcriptional complex hypoxia-inducible factor-1 (HIF-1) has emerged as an important mediator of gene expression patterns in tumors, although the range of responding genes is still incompletely defined. Here we show that the tumor-associated carbonic anhydrases (CAs) are tightly regulated by this system. Both CA9 and CA12 were strongly induced by hypoxia in a range of tumor cell lines. In renal carcinoma cells that are defective for the von Hippel-Lindau (VHL) tumor suppressor, up-regulation of these CAs is associated with loss of regulation by hypoxia, consistent with the critical function of pVHL in the regulation of HIF-1. Further studies of CA9 defined a HIF-1-dependent hypoxia response element in the minimal promoter and demonstrated that tight regulation by the HIF/pVHL system was reflected in the pattern of CA IX expression within tumors. Generalized up-regulation of CA IX in VHL-associated renal cell carcinoma contrasted with focal perinecrotic expression in a variety of non-VHL-associated
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FUNCTIONS OF CARBONIC ANHYDRASES. The presence of carbonic anhydrases in all living organisms probably originates because the components of the catalyzed reaction are involved in almost all metabolic processes. We suppose that the main reason for the abundance of CAs in nature is the ubiquitous involvement of bicarbonate buffers in aqueous media and then in the cytoplasm at every stage of evolution; these enzymes acceleration achieving appropriate pH, which is important for homeostasis of every living cell. The role of carbonic anhydrases in accelerating the conversion of inorganic forms of carbon was probably not their initial main function, but now it is established that these enzymes are critical regulators of the exchange of these forms in many metabolic processes.. Functions of Carbonic Anhydrases in Animals. Although the main purpose of this review is to consider the available experimental data and ideas concerning the role of CAs in higher plants, we should present, at least briefly, ...
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3MHL: 4-[N-(Substituted 4-pyrimidinyl)amino]benzenesulfonamides as inhibitors of carbonic anhydrase isozymes I, II, VII, and XIII
We have recently shown that CA IV expression in kidney cortex increased five-fold at the mRNA level (35) and 3- to 5-fold at the protein level (25) during postnatal maturation. A previous study showed a 19-fold increase in CA IV mRNA expression in rat lung between fetal day 20 and postnatal day 6, and a 40% postnatal increase to day 17, with no further increase (7). The postnatal increase was nearly comparable to what we have observed in rabbit lung (Fig. 5B). However, the increase in CA IV mRNA in kidney cortex is at least 10-fold and likely to account for the postnatal increment in protein (24). With most of the increase occurring during postnatal weeks 3-5, it is likely that the increase reflects the change in eating habits and a shift to an alkaline ash diet that requires a renal adaptation in transport. The large increase in CA IV may allow the kidney to handle the maturational increase in filtered load of bicarbonate and its proximal reabsorption.. Detailed studies of CA IX expression ...
Novelty, in brief, is represented by the intended elaboration of carborane, heteroborane and metallaborane compounds as active-site inhibitors of CA isoenzymes. All currently used inhibitors anhydrase inhibitors contain a sulfonamide or a sulfamate moiety connected to so called ring structure which is usually a 5- or 6-membered aromatic ring or conjugated ring system containing nitrogen, oxygen, and/or sulfur heteroatoms. The ring structure bears characteristics or functionality which modulates the affinity toward certain CA isoform. The use of three-dimensional boron cluster is a novel approach in development of isoform-specific CA inhibitors. Selected sulfamides incorporating cluster with inhibitory effects toward CAs (IC50 values in low micromolar and submicromolar range, some of the inhibitors being more than 50-times more selective toward the tumor specific CAIX than for CAII abundantly present in normal tissues ...
Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. CA IX is a transmembrane protein and is one of only two tumor-associated carbonic anhydrase isoenzymes known. It is expressed in all clear-cell renal cell carcinoma, but is not detected in normal kidney or most other normal tissues. It may be involved in cell proliferation and transformation. This gene was mapped to 17q21.2 by fluorescence in situ hybridization, however, radiation hybrid mapping localized it to 9p13-p12. [provided by RefSeq, Jun 2014 ...
beta-Lactam antibiotics are a broad class of antibiotics, consisting of all antibiotic agents that contain a beta-lactam ring in their molecular structures. Synthesis of beta-lactam analogs, which are containing dichloride atoms and N-methyl, N-aromatic rings, was achieved by Schiff bases and dichloroketene compounds. All the synthesized imines and beta-lactam analogs were tested against two physiologically relevant carbonic anhydrase isozymes (hCA I and II) and acetylcholinesterase (AChE). They demponstrated effective inhibitory profiles with K-i values in ranging of 3.22-11.18 nM against hCA I, 3.74-10.41 nM against hCA II, and 0.50-1.57 nM against AChE. On the other hand, acetazolamide and dorzolamide clinically used as CA inhibitors, showed K-i value of 170.34 and 129.26nM against hCA I, and 115.43 and 135.67 nM against hCA II, respectively. Also, tacrine used as standard AChE inhibitor showed Ki value of 5.70 nM against AChE ...
Blood and urine analyses: Visit 1: electrolytes, creatinine, estimated glomerular filtration rate (eGFR), glycemia, renin, angiotensin, aldosterone, plasma catecholamines, 24 h urinary sodium excretion, carbonic anhydrase activity and isoenzyme expression (in 50 randomly selected subjects), samples for genetic studies. Visit 2: electrolytes, creatinine, eGFR. Visit 3: complete blood count, electrolytes, creatinine, eGFR, glycemia, insulin, renin, angiotensin, aldosterone, plasma catecholamines, classic urinalysis, microalbuminuria, 24 h urinary sodium excretion, carbonic anhydrase activity and isoenzyme expression (in 50 subjects selected at Visit 1). Visit 4: electrolytes, creatinine, eGFR, glycemia, insulin, renin, angiotensin, aldosterone, plasma catecholamines, 24 h urinary sodium excretion, carbonic anhydrase activity and isoenzyme expression (in 50 subjects selected at Visit 1 ...
One of the four discrete isoenzymes of carbonic anhydrase hitherto characterized, CA III, has the lowest turnover rate and the greatest resistance to inhibition by sulphonamides. Streptozotocin-induced diabetes mellitus resulted in a reduction in acetazolamide-resistant activity of carbonic anhydrase in the liver, but not in tonic skeletal muscle, of adult male rats. The hepatic activity declined with apparent first-order kinetics [calculated rate constant (k) 0.089 day-1] to a minimum of approx. 6% of control values; the reduction in activity was moderated by administration of insulin. ...
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CAIX is a transmembrane protein and is a tumor-associated carbonic anhydrase isoenzyme. It is over-expressed in VHL mutated clear-cell renal cell carcinoma (ccRCC) and hypoxic solid tumors, but is low-expressed in normal kidney and most other normal tissues. It may be involved in cell proliferation and transformation. This gene is mapped to 9p13-p12.[7]. CAIX is a cellular biomarkers of hypoxia. Furthermore, recent studies examining the association between CAIX levels and various clinicopathological outcomes suggest that CAIX expression may also be a valuable prognostic indicator for overall survival[8] although this association has been questioned.[9]. ...
Anti-human Carbonic Anhydrase IX/CA9 antibody,Rabbit MAb. Applications for ELISA,FCM, fully validated. Quality guaranteed. Buy elite antibodies at up to 60% cost saving.
Anti-human Carbonic Anhydrase IX/CA9 antibody,Rabbit MAb. Applications for ELISA,IHC-P, fully validated. Quality guaranteed. Buy elite antibodies at up to 60% cost saving.
CAIX expression in bronchial trees and genital organs: In the bronchial trees high expression of CAIX was seen in the peribronchial immature mesenchymal cells a
Effect of Hyperglycemia on Erythrocyte Carbonic Anhydrase and Lactic Acid in Type II Diabetic Subjects. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
Carbonic anhydrase (CA) IX is a plasma membrane-associated member of the alpha-CA enzyme family, which is involved in solid tumor acidification. It is a marker of tumor hypoxia and a prognostic factor in several human cancers. An aberrant increase in CA IX expression in chronic hypoxia and during development of various carcinomas contributes to tumorigenesis through at least two mechanisms: pH regulation and cell adhesion control. Here we report the X-ray structure of the catalytic domain of CA IX in complex with a classical, clinically used sulfonamide inhibitor, acetazolamide. The structure reveals a typical alpha-CA fold, which significantly differs from the other CA isozymes when the protein quaternary structure is considered. Thus, two catalytic domains of CA IX associate to form a dimer, which is stabilized by the formation of an intermolecular disulfide bond. The active site clefts and the PG domains are located on one face of the dimer, while the C-termini are located on the opposite ...
Carbonic anhydrase 12, 0.1 ml. Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide.
The main findings of this study showed that the PCs exhibit OxSt and apoptosis responses when exposed to high glucose. Both high glucose-induced OxSt and apoptosis of PCs were rescued by pharmacological inhibition of mCA.. The PCs in immediate contact with the specialized EC of cerebral microvasculature comprising the BBB are vital for integrity of the latter and are especially susceptible to OxSt. Loss of PCs results in a focal increase in BBB permeability (Bonkowski et al., 2011). A close correlation between PC density and BBB permeability has been reported in PC-deficient adult mice (Armulik et al., 2010). Recently, we reported hyperglycemia-induced OxSt in the brain and cerebral PC loss in diabetic mice (Price et al., 2012). Clinical evidence suggests that diabetes-induced changes in the BBB may be a predisposing factor for Alzheimers disease (Ristow, 2004) and people suffering from both types of diabetes have an increased risk of cognitive impairment (Whitmer, 2007; Bruce et al., 2008; ...
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Recently, a convincing body of evidence has accumulated suggesting that the overexpression of carbonic anhydrase isozyme IX (CA IX) in some cancers contributes to the acidification of the extracellular matrix, which in turn promotes the growth and metastasis of the tumor. These observations have made CA IX an attractive drug target for the selective treatment of certain cancers. Currently, there is no available X-ray crystal structure of CA IX, and this lack of availability has hampered the rational design of selective CA IX inhibitors. In light of these observations and on the basis of structural alignment homology, using the crystal structure of carbonic anhydrase II (CA II) and the sequence of CA IX, a double mutant of CA II with Ala65 replaced by Ser and Asn67 replaced by Gln has been constructed to resemble the active site of CA IX. This CA IX mimic has been characterized kinetically using (18)O-exchange and structurally using X-ray crystallography, alone and in complex with five CA ...
ESCUDERO-ALMANZA, Dalila Jacqueline et al. Carbonic Anhydrase and Zinc in Plant Physiology. Chilean J. Agric. Res. [online]. 2012, vol.72, n.1, pp.140-146. ISSN 0718-5839. http://dx.doi.org/10.4067/S0718-58392012000100022.. Carbonic anhydrase (CA) (EC: 2.4.1.1) catalyzes the rapid conversion of carbon dioxide plus water into a proton and the bicarbonate ion (HCO3-) that can be found in prokaryotes and higher organisms; it is represented by four different families. Carbonic anhydrase is a metalloenzyme that requires Zn as a cofactor and is involved in diverse biological processes including pH regulation, CO2 transfer, ionic exchange, respiration, CO2 photosynthetic fixation, and stomatal closure. Therefore, the review includes relevant aspects about CA morphology, oligomerization, and structural differences in the active site. On the other hand, we consider the general characteristics of Zn, its geometry, reactions, and physiology. We then consider the CA catalysis mechanism that is carried out ...
Background: In HCC, hypoxia and MET can promote tumor progression and induce resistance to radiation, chemo or targeted therapies. The aim of this study was to correlate MET and hypoxia marker carbonic anhydrase 9 (CA9) expression levels by immunohistochemistry with clinicopathological characteristics and disease-free survival (DFS) in patients with HCC.. Material and methods: One-hundred HCC resection specimens were evaluated by immunohistochemistry for MET (clone sp44, Ventana) and CA9 (rabbit polyclonal) expression. For automated evaluation, we elaborated our own macro using ImageJ software, and compared it with H- and MetMab validated scores. METhigh and CA9high expression were defined as moderate to strong staining. Staining results were correlated with clinicopathological characteristics. Univariate analyses were performed using Fishers exact or chi square tests, and multivariate analyses using Cox regression model. Median DFS (mDFS) were calculated by Kaplan-Meier method. MET ...
Carbonic anhydrase IX (CAIX) is a cell surface enzyme that is over-expressed in approximately 95% of clear cell renal cell carcinomas (ccRCCs), the most common renal cancer. CAIX is also a surrogate marker of hypoxic tumors for various human cancers; however, a clinically viable molecular imaging agent targeting CAIX is not available. We have synthesized and performed in vitro and in vivo evaluation of a dual-motif, low-molecular-weight inhibitor of CAIX, [64Cu] XYIMSR-06, for imaging CAIX expression on ccRCC tumors using positron emission tomography (PET). [64Cu] XYIMSR-06 was synthesized in two steps from reported dual-motif precursor 1. Upon radiolabeling, [64Cu] XYIMSR-06 was evaluated in immunocompromised mice bearing CAIX-expressing SK-RC-52 tumors for in vivo PET imaging and biodistribution. [64Cu] XYIMSR-06 was generated in radiochemical yields of 51.0 ± 4.5% (n = 5) and specific radioactivity of 6.0 GBq/μmol (170Ci/mmol ± 70, n = 5). Tumor could be visualized on PET images by 1 h ...
SWISS-MODEL Template Library (SMTL) entry for 3hlj.1. Crystal structure of human carbonic anhydrase isozyme II with 3-methylthiobenzimidazo[1,2-c][1,2,3]thiadiazol-7-sulfonamide
Rabbit recombinant monoclonal Carbonic Anhydrase IX antibody [SP106] validated for IHC, Flow Cyt and tested in Human. Immunogen corresponding to synthetic…
The high metabolic rate required for tumor growth often leads to hypoxia in poorly-perfused regions. Hypoxia activates a complex gene expression program, mediated by hypoxia inducible factor 1 (HIF1alpha). One of the consequences of HIF1alpha activation is up-regulation of glycolysis and hence the production of lactic acid. In addition to the lactic acid-output, intracellular titration of acid with bicarbonate and the engagement of the pentose phosphate shunt release CO(2) from cells. Expression of the enzyme carbonic anhydrase 9 on the tumor cell surface catalyses the extracellular trapping of acid by hydrating cell-generated CO(2) into [see text] and H(+). These mechanisms contribute towards an acidic extracellular milieu favoring tumor growth, invasion and development. The lactic acid released by tumor cells is further metabolized by the tumor stroma. Low extracellular pH may adversely affect the intracellular milieu, possibly triggering apoptosis. Therefore, primary and secondary active transporters
Abstract. Synthetic peptides that self-assemble into well-defined structures with a cross-β arrangement are called amyloid-like fibrils. Amyloids are associated with a list of disorders and neuro-degenerative diseases, such as Alzheimers and Parkinson`s disease. We previously showed that amyloid-like nanofibrils with a repeating motif "IHIH" were functional fibrils. They were able to bind a metal ion through imidazole moieties and mimic the native carbonic anhydrase enzyme by hydrolysing the CO2 molecule. Thus, these synthetic amyloid fibrils were suggest-ed to be good candidates to moderate and update the modern enzymatic molecules. This study aims to shed a light on the stability of these amyloid nanofibrils over a study period of 25 days, in the presence/absence of a metal ion. The work continued for approximately 7 months in the Biochemistry department, School of Life Sciences at the University of Sussex in the United Kingdom. A set of designed peptides with a repeating motif "IHIH" were ...
Chemically, topiramate is a sulfamate modified fructose diacetonide - a rather unusual chemical structure for a pharmaceutical. Topiramate is quickly absorbed after oral use. Most of the drug (70%) is excreted in the urine unchanged. The remainder is extensively metabolized by hydroxylation, hydrolysis, and glucuronidation. Six metabolites have been identified in humans, none of which constitutes more than 5% of an administered dose. Several cellular targets have been proposed to be relevant to the therapeutic activity of topiramate.[38] These include (1) voltage-gated sodium channels; (2) high-voltage-activated calcium channels; (3) GABA-A receptors; (4) AMPA/kainate receptors; and (5) carbonic anhydrase isoenzymes. There is evidence that topiramate may alter the activity of its targets by modifying their phosphorylation state instead of by a direct action.[39] The effect on sodium channels could be of particular relevance for seizure protection. Although topiramate does inhibit ...
We report the cloning, purification and characterization of the full domain of carbonic anhydrase (CA, EC 4.2.1.1) from Plasmodium falciparum, which incorporates 358 amino acid residues (from 181 to 538, in the sequence of this 600 amino acid long protein), called PfCAdom. The enzyme, which belongs to the η-CA class showed the following kinetic parameters: kcat of 3.8×10(5)s(-1) and kcat/Km of 7.2×10(7)M(-1)×s(-1), being 13.3 times more effective as a catalyst compared to the truncated form PfCA. PfCAdom is more effective than the human (h) isoform hCA I, being around 50% less effective compared to hCA II, one of the most catalytically efficient enzymes known so far. Intriguingly, the sulfonamides CA inhibitors generally showed much weaker inhibitory activity against PfCAdom compared to PfCA, prompting us to hypothesize that the 69 amino acid residues insertion present in the active site of this η-CA is crucial for the active site architecture. The best sulfonamide inhibitors for PfCAdom ...
Carbonic anhydrase (CA; EC 4.2.1.1) is a zinc containing enzyme which catalyzes a reversible reaction to form bicarbonate from carbon dioxide and water [1, 2]. By facilitating the interconversion between CO2 and bicarbonate in vivo, CA activity was proposed to be required to ensure adequate level of CO2or HCO3- as the substrates for other enzymes [3]. Therefore, CAs have been found to play an essential role in a series of fundamental biological processes such as photosynthesis, respiration, pH homeostasis and ion transport [4]. Based on the origins and structural features, CAs are divided into six classes, termed α, β, γ, δ, ε and ζ, respectively [5]. The α-CAs were found in mammals, algae and prokaryotes to facilitate the exchange of CO2 in the respiratory cycle. The β-CAs were characterized in higher plants, algae and prokaryotes, and those in higher plants have been reported to play a critical role during photosynthesis [6]. The γ-class was first identified in the thermophilic ...
Creative Biolabs provides Lenti-Carbonic anhydrase IX (CA9) CAR (scFv-CD3ζ, G36) Viral Particle product for Biopharmaceutical research,preclinical and clinical trials.
Carbonic anhydrase (CA) from erythrocytes of the pink salmon, Onchorhyncus gorbushka, was purified using chloroform-ethanol extraction and Sephadex G-75 gel filtration. A single, high specific-activity CA isozyme having a molecular weight of 29,000 was found. The enzyme sedimented as a ...read more ...
At normal physiological pH, ~7.4, pHLIPs exist in States I and II, interacting with the outside surface of cells but exchanging with the aqueous surroundings. A number of pathological conditions produce a more acidic extracellular environment due to the affects of hypoxia, ischemia, or abnormal metabolic processes. A significant example of such acidity is in solid tumors. Due to their heightened metabolic activity, their compromised blood supply, membrane bound carbonic anhydrase activity, and to the Warburg effect, cancerous tumors produce a significantly acidic extracellular environment of around pH 6. In a serendipitous coincidence, this pH is sufficiently low to protonate the aspartic acid residues in pHLIPs transmembrane domain, causing pHLIPs to insert into cells, where they are relatively stable and thereby accumulate in the cells of acidic tumors. ...
We have studied lactic acid transport in the fast mouse extensor digitorum longus muscles (EDL) by intracellular and cell surface pH microelectrodes. The role of membrane-bound carbonic anhydrases (CA) of EDL in lactic ...
The 2016 Spring Meeting of the Japan Poultry Science Association was held at Nippon Veterinary and Life Science University at Musashino, Tokyo, on March 30. The meeting included a total of 58 paper presentations and luncheon seminars as well as council and general meetings.. During the Spring Meeting, four awards were given under the category of students or members aged 30 or below for the following excellent presentations: 1) Biochemical and functional analysis of membrane rafts in chicken sperm by Ai Ushiyama (Tsukuba University); 2) Dynamics of L cells along the crypt-villous axis in the chicken ileum by Kei Nishimura (Shinshu University); 3) Effects of trehalose added feed on cooked odors in broiler thigh meat by Shoji Kakuta (Hayashibara Co., Ltd.); and 4) Characteristic expression on carbonic anhydrases 4 in the eggshell gland of laying hens under heat stress conditions by Yuuki Hosokawa (Tokyo University of Agriculture and Technology). JPSA congratulated the presenters who ...
Background: Intratumorous hypoxia triggers a broad cellular response mediated by the transcription factor hypoxia inducible factor 1 (HIF-1). HIF-1a concentrations increase during breast carcinogenesis, and are associated with poor prognosis. An earlier study noted two HIF-1a overexpression patterns: diffuse scattered throughout the tissue and confined to perinecrotic cells. Aims: To investigate ... read more the prognostic impact of these different HIF-1a overexpression patterns in relation to its downstream effectors carbonic anhydrase (CA) IX and glucose transporter 1 (GLUT-1). Methods: HIF-1a, CA IX, and GLUT-1 expression was studied by immunohistochemistry, including double staining for CA IX and HIF-1a. Clinical data included disease free survival, lymph node status, and tumour size. Results: HIF-1a overexpression (44% of cases) had a perinecrotic (13.5%) or diffuse staining pattern (30.5%). CA IX expression was detectable in 12.5% of breast cancers, whereas GLUT-1 expression was seen in ...
PRIMARY OBJECTIVE:. I. Compare the progression-free survival of patients with stage IB, IIA, IIB, IIIB, or IVA carcinoma of the cervix treated with cisplatin and radiotherapy with vs without tirapazamine.. SECONDARY OBJECTIVES:. I. Compare overall survival of patients treated with these regimens. II. Compare the toxicity of these regimens in these patients.. TERTIARY OBJECTIVES:. I. Correlate study treatment with tumor expression of carbonic anhydrase IX (CA-IX) and recurrence-free survival, overall survival, or metastasis in patients treated with these regimens.. II. Correlate expression of CA-IX, hypoxia inducible factor-1α, CD-31, thrombospondin-1, CD-105, or vascular endothelial growth factor (VEGF) in primary tumor tissue with recurrence-free survival, overall survival, or metastasis in patients treated with these regimens.. III. Correlate pre-treatment and/or post-treatment serum concentrations of angiogenic markers including angiogenin or VEGF with recurrence-free survival, overall ...
OBJECTIVE: Taste sensitivity is one of the most important biological determinants of food choice. Three SNPs of the TAS2R38 gene (rs713598, rs1726866, and rs10246939) give rise to two common haplotypes: PAV and AVI. These haplotypes, as well as an SNP within the CA6 gene (rs2274333) that encodes carbonic anhydrase VI (CA6), correlate with bitterness perception. The extent of consumption of bitter food may influence some health outcomes. The aim of this study is thus to investigate the impact of the TAS2R38 and CA6 genetic polymorphisms on the choice of bitter food, BMI, blood lipoprotein, and glucose concentrations as well as systemic inflammation in elderly women. METHODS: The associations between the TAS2R38 diplotype, CA6 genotype, and the intake of bitter-tasting foods were studied in a group of 118 Polish women over 60 years of age. The intake of Brassica vegetables, grapefruit, and coffee was assessed using a food frequency questionnaire. Biochemical parameters were measured using the ...
Based on well documented evidence, Matrixxs Zicam caused anosmia (loss of smell) as a result of a toxic destruction of the olfactory epithelium. The implicated component or ingredient is zinc that, while critical for maintenance of normal smell function through its action as a cofactor in carbonic anhydrase VI, given directly into the nostrils at ...
The IUPHAR/BPS Guide to Pharmacology. carbonic anhydrase 12 - 4.2.1.1 Carbonate dehydratases. Detailed annotation on the structure, function, physiology, pharmacology and clinical relevance of drug targets.
Objective: The purpose of this experiment was to complete the dehydration reaction of 2-methylcyclohexanol and to identify b...
Well, I am another co-author of the PNAS LSD paper and I find Kastrups analysis of the media focusing towards increases in brain activity fitting materialism, and therefore reinforcing their values and worldview interesting. However, I think it is far too simplistic to discuss such a complex and difficult topic of brain and consciousness using the simple notions and language of more or less brain activity. It is much more complex than that. Decreases in power spectra do not necessarily translate to less brain activity. It can be that the changes are in subtle synchs between millions of neurons over millisecond time range, which were not analyzed in depth (the plots for the MEG figure show averaged results over 3 second time epochs, a considerable long time for neurons to synch or desynch). This could imply that the language less brain activity may not fit the detected reductions in power. This would thus weaken the argument that the data is at odds with materialism (which is a possible ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
I tiazidici, come lidroclorotiazide favorire la perdita di acqua dal corpo (diuretici). Essi inibiscono la Na + / Cl-riassorbimento da parte del tubulo contorto distale nei reni. I diuretici tiazidici anche causare la perdita di potassio e un aumento di livelli sierici di acido urico. I diuretici tiazidici sono spesso usati per trattare lipertensione, ma i loro effetti ipotensivi non sono necessariamente a causa della loro attività diuretica. I diuretici tiazidici hanno dimostrato di prevenire ipertensione correlata morbilità e mortalità anche se il meccanismo non è completamente nota. I diuretici tiazidici provocare vasodilatazione mediante lattivazione canali del potassio calcio-attivata (conduttanza di grandi dimensioni) in vascolare muscolatura liscia e inibendo vari carbonica anhydrases nel tessuto vascolare ...
L-arginine, Disease, Patients, Arginine, Nitric Oxide, Carbonic Anhydrase, Isoforms, Inhibition, Sulfonamides, Active Site, Heart, and Concentrations
View Notes - Bild 1 week2 problems from BILD 1 at UCSD. 1 Kang Ko OH: Wed., 11am-11:50am at CLICS 2 nd floor [email protected] II. The following picture shows a dehydration reaction of nucleotides. 1.
References for Abcams Recombinant Human CA8 protein (ab123192). Please let us know if you have used this product in your publication
Most loss-of-function diseases are caused by aberrant folding of important proteins. These proteins often misfold due to inherited mutations. The rare disease marble brain disease (MBD) also known as carbonic anhydrase II deficiency syndrome (CADS) can manifest in carriers of point mutations in the human carbonic anhydrase II (HCA II) gene. We have over the past 10-15 years studied the folding, misfolding and aggregation of the enzyme human carbonic anhydrase II. In summary our HCA II folding studies have shown that the protein folds via an intermediate of molten-globule type, which lacks enzyme activity and the molten globule state of HCA II is prone to aggregation. One mutation associated with MBD entails the His107Tyr (H107Y) substitution. We have demonstrated that the H107Y mutation is a remarkably destabilizing mutation influencing the folding behavior of HCA II. A mutational survey of position H107 and a neighboring conserved position E117 has been performed entailing the mutants H107A, ...
Looking for Carbonic anhydrase iv? Find out information about Carbonic anhydrase iv. An enzyme which aids carbon dioxide transport and release by catalyzing the synthesis, and the dehydration, of carbonic acid from, and to, carbon dioxide... Explanation of Carbonic anhydrase iv
Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of photochromic pharmacophores we were interested in the exploration of azobenzene-containing sulfonamides to block the catalytic activity of human carbonic anhydrase II (hCAII). Herein, we report the synthesis and in vitro evaluation of a small library of nine photochromic sulfonamides towards hCAII. All molecules are azobenzene-4-sulfonamides, which are substituted by different functional groups in the 4 -position and were characterized by X-ray crystallography. We aimed to investigate the influence of electrondonating or electron-withdrawing substituents on the inhibitory constant Ki. With the aid of an hCAII crystal structure bound to one of the synthesized azobenzenes, we found that the electronic structure does not strongly affect inhibition. Taken together, all compounds are strong blockers of hCAII with K-i = 25-65 nM that are potentially photochromic and thus combine ...
Cryptococcus neoformans, a fungal pathogen of humans, causes fatal meningitis in immunocompromised patients. Its virulence is mainly determined by the elaboration of a polysaccharide capsule surrounding its cell wall. During its life, C. neoformans is confronted with and responds to dramatic variations in CO2 concentrations; one important morphological change triggered by the shift from its natural habitat (0.033% CO2) to infected hosts (5% CO2) is the induction of capsule biosynthesis. In cells, CO2 is hydrated to bicarbonate in a spontaneous reaction that is accelerated by carbonic anhydrases. Here we show that C. neoformans contains two beta-class carbonic anhydrases, Can1 and Can2. We further demonstrate that CAN2, but not CAN1, is abundantly expressed and essential for the growth of C. neoformans in its natural environment, where CO2 concentrations are limiting. Structural studies reveal that Can2 forms a homodimer in solution. Our data reveal Can2 to be the main carbonic anhydrase and ...
BACKGROUND: Carbonic anhydrase IX (CA9) is reportedly overexpressed in several types of carcinomas, but little is known about the expression pattern of CA9 in osteosarcoma. We aimed to assess the prevalence of CA9 expression and its prognostic implications in osteosarcoma patients. METHODS: We compared immunohistochemical expression of CA9 between conventional, high-grade and low-grade, central osteosarcomas. Specimens were obtained before chemotherapy and stained with anti-human CA9 antibody. We also evaluated the histologic grade, presence of metastasis, and patient prognosis. RESULTS: Among 38 samples of conventional high-grade osteosarcoma, 22 (57.9%) tumors displayed CA9 overexpression. Twenty-five cases of low-grade central osteosarcomas were all negative (p < 0.0001). CA9 expression was significantly associated with the presence of metastasis (p = 0.0010). The overall survival rate was significantly reduced with increased CA9 expression (p = 0.0012), higher histologic grade (p < 0.0001), ...
Most loss-of-function diseases are caused by aberrant folding of important proteins. These proteins often misfold due to inherited mutations. The rare disease marble brain disease (MBD) also known as carbonic anhydrase II deficiency syndrome (CADS) can manifest in carriers of point mutations in the human carbonic anhydrase II (HCA II) gene. We have over the past 10-15 years studied the folding, misfolding and aggregation of the enzyme human carbonic anhydrase II. In summary our HCA II folding studies have shown that the protein folds via an intermediate of molten-globule type, which lacks enzyme activity and the molten globule state of HCA II is prone to aggregation. One mutation associated with MBD entails the His107Tyr (H107Y) substitution. We have demonstrated that the H107Y mutation is a remarkably destabilizing mutation influencing the folding behavior of HCA II. A mutational survey of position H107 and a neighboring conserved position E117 has been performed entailing the mutants H107A, ...
Inhibition of ammonia excretion (J(amm)) is a common response to Cu exposure in freshwater (FW) and seawater (SW) organisms. To determine the mechanism of this response, a euryhaline species of guppy (Poecilia vivipara) was exposed to 20 μg Cu/l in FW (0 ppt) and SW (25 ppt) for 96 h. In both salinities, Cu transiently inhibited ammonia excretion (J(amm)) followed by a full recovery by the end of the 96 h exposure. The activities of Na(+)/K(+)-ATPase, H(+)-ATPase, and carbonic anhydrase (CA) were examined in the gills at 12 and 96 h of Cu exposure. In both salinity acclimations, CA activity was significantly inhibited following 12h of Cu exposure in P. vivipara, marking the first in vivo evidence of Cu-induced inhibition of CA in fish. Moreover, the inhibition and recovery of this enzyme were correlated with the inhibition and recovery of J(amm) in both salinity acclimations. The blockade of CA potentially acts as a common mechanism of J(amm) inhibition in FW and SW. There were no significant ...
Mono- and Stereopictres of 5.0 Angstrom coordination sphere of Zinc atom in PDB 1z9y: Carbonic Anhydrase II in Complex With Furosemide As Sulfonamide Inhibitor
Sigma-Aldrich offers abstracts and full-text articles by [Vaida Morkūnaitė, Joana Gylytė, Asta Zubrienė, Lina Baranauskienė, Miglė Kišonaitė, Vilma Michailovienė, Vaida Juozapaitienė, Matthew J Todd, Daumantas Matulis].
Uppsala University, Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology. ...
The plant hormone salicylic acid (SA) is required for defense responses. NON EXPRESSER OF PATHOGENESIS RELATED 1 (NPR1) and NON RECOGNITION OF BTH-4 (NRB4) are required for the response to SA in Arabidopsis (Arabidopsis thaliana). Here, we isolated several interactors of NRB4 using yeast two-hybrid assays. Two of these interactors, βCA1 and βCA2, are β-carbonic anhydrase family proteins. Since double mutant βca1 βca2 plants did not show any obvious phenotype, we investigated other βCAs and found that NRB4 also interacts with βCA3 and βCA4. Moreover, several βCAs interacted with NPR1 in yeast, including one that interacted in a SA-dependent manner. This interaction was abolished in loss-of-function alleles of NPR1. Interactions between βCAs and both NRB4 and NPR1 were also detected in planta, with evidence for a triple interaction, NRB4-βCA1-NPR1. The quintuple mutant βca1 βca2 βca3 βca4 βca6 showed partial insensitivity to SA. These findings suggest that one of the functions of carbonic
In the catalysis of the hydration of carbon dioxide and dehydration of bicarbonate by human carbonic anhydrase II (HCA II), a histidine residue (His64) shuttles protons between the zinc-bound solvent molecule and the bulk solution. To evaluate the effect of the position of the shuttle histidine and …
To further assess our results, we performed a literature review of the genes reported by at least seven studies in the cancer versus normal comparison to determine if any have been shown to have diagnostic and/or prognostic utility in colorectal cancer. The most consistently reported differentially expressed gene in our meta-analysis was carbonic anhydrase II (CA2), which was reported as down-regulated in 11 studies. Along with carbonic anhydrase I, CA2 has been shown to have prognostic significance where the expression of both enzymes was related to the metastatic aggressiveness of colorectal cancer (23). Similarly, the potential diagnostic utility of CA2 was shown in a study in which the average level of fecal CA2 in colorectal cancer patients was shown to be significantly greater than those in the control group (24). Immunohistochemistry has been done on colorectal tumor and healthy mucosa tissue to monitor the protein levels of four carbonic anhydrases, among them CA2 (25). That study showed ...
This study tests the hypothesis that the increase in blood PCO2 and associated respiratory acidosis after exhaustive exercise play an important role in stimulating ventilation during post-exercise recovery in fish. Injection of bovine carbonic anhydrase (10 mg kg-1) into the bloodstream of rainbow trout caused a persistent 40 % increase in the HCO3- dehydration capacity of the blood. The treatment was designed to increase CO2 excretion and therefore to reduce PCO2 build-up and acidosis after exercise. Aerobic and anaerobic swimming performance were not affected by carbonic anhydrase, and there were only very minor effects on arterial blood acid­base status in resting fish. However, carbonic anhydrase attenuated post-exercise increases in PaCO2 and decreases in pHa by about 50 % without altering arterial O2 variables, red cell swelling or the intracellular pH of the brain or muscle tissues. The effects on arterial pH (pHa) resulted largely from alleviation of the increase in PaCO2. In ...
In vertebrates, carbonic anhydrases (CAs) play important roles in ion transport and pH regulation in many organs, including the eyes, kidneys, central nervous system, and inner ear. In aquatic organis
Carbonic anhydrase 12 is an enzyme that in humans is encoded by the CA12 gene. Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. This gene product is a type I membrane protein that is highly expressed in normal tissues, such as kidney, colon and pancreas, and has been found to be overexpressed in 10% of clear cell renal carcinomas. Two transcript variants encoding different isoforms have been identified for this gene. Loss of function mutations in the CAXII gene result in defects in fluids and carbonate secretions in the following diseases: 1) Cystic fibrosis-like syndrome with normal cystic fibrosis transmembrane conductance regulator (CFTR) protein levels 2) Pancreatitis 3) Sjögrens syndrome 4) Xerostomia or ...
Alfa Aesar™ 4-Nitrophenyl acetate, 98+% 10g Alfa Aesar™ 4-Nitrophenyl acetate, 98+% Nitrog to Nitrophenylacet -Organics
Hyperventilation is a difficult diagnosis to make clinically and that is why having an objective test of hyperventilation is so useful. People who hyperventilate deplete their levels of red cell carbonic anhydrase and the ratio between the activity and the protein gives us a good indication of whether or not hyperventilation is a problem. Hyperventilation is also difficult to treat and so this test tells us how much effort we have to put in to correcting this. Essentially, there is a two-pronged approach - firstly biochemical and secondly physical: Biochemically, red cell carbonic anhydrase is a zinc dependent enzyme and will be depleted simply by zinc deficiency. Furthermore, a low red cell carbonic anhydrase drives hyperventilation and so this is another example of one of the many vicious cycles seen in patients with chronic fatigue. Zinc is best absorbed at night and I recommend taking 30mg last thing at night on an empty stomach. This should be in addition to zinc taken in my physiological ...
Looking for online definition of CA-IX in the Medical Dictionary? CA-IX explanation free. What is CA-IX? Meaning of CA-IX medical term. What does CA-IX mean?
We investigated the expression of CA IX in a series of oligodendroglial brain tumors. We found that CA IX is expressed in most of these tumors and that it has an independent prognostic value, predicting a poor outcome. In addition, CA IX(+) tumors had decreased cell proliferation compared to CA IX(-) tumors.. Chromosomal loss of 1p and 19q is a common genotypic change in oligodendrogliomas. It is commonly used as a tool to make more precise decisions concerning the treatment. Recently, it has become clear, however, that defects in single chromosomes, genes, or even the sequential acquisition of mutations, are not the entire story in tumorigenesis, given that many cancer susceptibility genes show a high degree of tissue specificity in their association with neoplastic transformation. Also in oligodendrogliomas and other malignant brain tumors, the acquisition of a complete neoplastic phenotype is caused by the activation of several oncogenes and the inactivation of several growth-suppressor ...
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BioAssay record AID 644085 submitted by ChEMBL: Inhibition of human carbonic anhydrase 2 using 4-nitrophenylacetate as substrate after 3 mins using spectrophotometry by Lineweaver-Burk plot analysis.
en] Acidosis, Renal Tubular/chemically induced/enzymology ; Anticonvulsants/adverse effects/therapeutic use ; Carbonic Anhydrases/metabolism ; Female ; Fructose/adverse effects/analogs & derivatives/therapeutic use ; Humans ; Kidney/drug effects/enzymology/pathology ; Middle Aged ; Migraine Disorders/drug therapy ; Models, ...
A major challenge in photodynamic cancer therapy (PDT) is avoiding PDT-induced hypoxia, which can lead to cancer recurrence and progression through activation of various angiogenic factors and significantly reduce treatment outcomes. Reported here is an acetazolamide (AZ) conjugated BODIPY photosensitizer (AZ-BPS) designed to mitigate the effects of PDT-based hypoxia by combining the benefits of anti-angiogenesis therapy with PDT. AZ-BPS showed specific affinity to aggressive cancer cells (MDA-MB-231 cells) that overexpress carbonic anhydrase IX (CAIX). It displayed enhanced photo-cytotoxicity compared to a reference compound, BPS, which is an analogous PDT agent that lacks an acetazolamide unit. AZ-BPS also displayed an enhanced in vivo efficacy in a xenograft mouse tumor regrowth model relative to BPS, an effect attributed to inhibition of tumor angiogenesis by both PDT-induced ROS generation and CAIX knockdown. AZ-BPS was evaluated successfully in clinical samples collected from breast cancer ...
Mlig034227.g3 {REF} {Length: 2733} {Pfam: Tubulin/FtsZ family, GTPase domain [PF00091.25, score=231.9]; Tubulin C-terminal domain [PF03953.17, score=146.9]; Misato Segment II tubulin-like domain [PF10644.9, score=25.7]} {Human: ENSG00000188229, TUBB4B, tubulin beta 4B class IVb, [RH, Score=920, Expect=0.0]; ENSG00000137285, TUBB2B, tubulin beta 2B class IIb, [RH, Score=908, Expect=0.0]; ENSG00000104833, TUBB4A, tubulin beta 4A class IVa, [RH, Score=905, Expect=0.0]; ENSG00000232575, TUBB, tubulin beta class I, [RH, Score=903, Expect=0.0]; ENSG00000196230, TUBB, tubulin beta class I, [RH, Score=903, Expect=0.0]; ENSG00000183311, TUBB, tubulin beta class I, [RH, Score=903, Expect=0.0]; ENSG00000227739, TUBB, tubulin beta class I, [RH, Score=903, Expect=0.0]; ENSG00000235067, TUBB, tubulin beta class I, [RH, Score=903, Expect=0.0]; ENSG00000229684, TUBB, tubulin beta class I, [RH, Score=903, Expect=0.0]; ENSG00000137267, TUBB2A, tubulin beta 2A class IIa, [RH, Score=903, Expect=0.0]; ...
Glaucoma is a serious disease associated with increased intraocular pressure which often leads to blindness. One of the ways to treat glaucoma is to reduce aqueous humour secretion in the ciliary body of the eye by suppressing (inhibiting) activity of special enzymes - carbonic anhydrases. Russian scientists from RUDN University have designed new compounds that can effectively reduce intraocular pressure by isoform selective inhibiting human carbonic anhydrase. The results of the study were published in the prestigious Bioorganic Chemistry journal.
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
2foy: Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with two-prong inhibitors reveal the molecular basis of high affinity.
Zinc. Zinc is a component of certain important enzymes, such as carbonic anhydrase, lactic dehydrogenase, alkaline phosphatase, DNA and RNA polymerases, and d-aminolevulinic acid dehydratase. Zinc is obtained primarily through food. About 30% of that ingested is absorbed in the small intestine. About 80% of zinc in blood is found in RBCs, mostly as part of the enzyme carbonic anhydrase. Of that portion not in RBCs, about 50% is bound to albumin, about 30% is bound to alpha-2 macroglobulin or transferrin, and about 5% is bound to histidine and certain other amino acids, leaving about 15% free in plasma. Excretion occurs predominately in the stool, with a much smaller amount excreted in urine and sweat.. Zinc deficiency is usually not clinically evident until it becomes severe. Severe deficiency may produce growth retardation, delayed sexual development, acrodermatitis enterohepatica (dermatitis, diarrhea, and alopecia), decreased taste acuity, and poor wound healing. Acrodermatitis enterohepatica ...
Recombinant Carbonic Anhydrase VII (CA7) Protein. Species: Rat (Rattus). Source: Escherichia coli (E. coli). Order product ABIN6302725.
SWISS-MODEL Template Library (SMTL) entry for 1t9n.1. Effect of Shuttle Location and pH Environment on H+ Transfer in Human Carbonic Anhydrase II
Background and aims: Expression of carbonic anhydrase IX (CA9), an enzyme expressed in response to hypoxia, acidosis and oncogenic alterations, is reported to be a prognostic factor in HCC patients. Here we evaluated serum CA9 levels in HCC and cirrhosis patients. Methods: HCC and cirrhosis patients were prospectively recruited and CA9 levels were determined. CA9 levels were compared to stages of cirrhosis and HCC stages. The association of the CA9 levels and overall survival (OS) was assessed. Furthermore, immunohistochemical CA9 expression in HCC and cirrhosis was evaluated. Results: 215 patients with HCC were included. The median serum CA9 concentration in patients with HCC was 370 pg/ml and significantly higher than in a healthy cohort. Patients with advanced cancer stages (BCLC and ALBI score) had hid significant higher levels of CA9 in the serum. HCC patients with high serum CA9 concentrations (,400 pg/ml) had an increased mortality risk (hazard ratio (HR) 1.690, 95% confidence interval ...
Saccharin shows considerable promise for its ability to inhibit an enzyme upregulated in many cancers, helping tumor cells survive and metastasize, said Robert McKenna, a professor of biochemistry and molecular biology in the UF College of Medicine. After testing its effectiveness on cancer cells, researchers believe saccharin could eventually lead to the development of drugs that treat highly aggressive cancers affecting the breast, liver, prostate, kidney and pancreas. The findings were published recently in the journal Bioorganic & Medicinal Chemistry and are being presented Wednesday at the American Chemical Society convention in Denver. The discovery might never have happened if not for Brian Mahon, a curious UF graduate research assistant. He wanted to know how saccharin might affect the enzyme, carbonic anhydrase IX, which is found in aggressive cancers. But Mahon didnt want to wait a week for an order of pure saccharin to arrive at the lab. He bounced an idea off Jenna Driscoll, an ...
Method of Action. Zinc is an important metallic constituent of the enzyme carboxypeptidase A, a pancreatic enzyme active in protein degradation. Zinc is found in highest concentration in the liver, with lesser amounts found in the pancreas, kidney, and pituitary gland. Zinc absorption occurs primarily in the small intestine. Zinc-binding ligand molecules act to transport zinc across the mucosal cells of the intestine, where it is picked up by albumin molecules for transport to the liver and other organs.. Zinc is a constituent of the enzyme carbonic anhydrase. This enzyme is, in turn, a constituent of red blood cells and gastric juices, and plays an important role in the deposition of calcium salts in teeth and bones.. The enzyme alcohol dehydrogenase contains zinc and is essential for the conversion of alcohol to an aldehyde, thereby facilitating alcohol metabolism in the liver. The function of this enzyme and its relationship to the development of liver cirrhosis is conspicuously tied to ...
Metal ions confer structural stability and reactivity to a large number of proteins that use the amino acids histidine (His) and cysteine (Cys) to form stable metal-ligand complexes. The stability of metal-His and metal-Cys interactions and their global effect on protein structure have been quantified using differential scanning calorimetry (DSC) and complementary spectroscopic methods. In the first study, the Zn??-containing enzyme carbonic anhydrase (CA), where the metal is coordinated by three His residues, the native Zn??-, and the Co??-,Cd??-,Cu??-,Ni??-, and Mn??-substituted enzymes are all more stable than the apo (metal-free) form, with the magnitude of the additional stability depending on the metal ion. DFT calculations reveal that constaints of the protein environment distort and destabilize the metal coordination at the His? active site, and the magnitude of this distortion correlates inversely with the CA stability. In a second study, the thermodynamics of the stability provided by ...
Purified Mouse anti-CA72-4 Monoclonal Antibody from Creative Biomart. Anti-CA72-4(CA72-4, Cancer Antigen 72-4) can be used for WB,ELISA.
The trailer for Paranormal Activity spinoff, The Marked Ones, is finally here with the upmost intention of making your heart skip a beat.
2h15: Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue.
Question 10: This is the reaction that integrates CO2 into ________ sugars during photosynthesis, and can use only the CO2 form of carbon, not carbonic acid or bicarbonate. ...
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This study focused on the synthesis and characterization of hydrazide ligands and their respective Pd(II) complexes and used high throughput screening to determine their α-glucosidase and carbonic anhydrase II enzyme inhibition activities. The physical, analytical (elemental analyses for C, H, N and Pd) and spectral (FT-IR, 1H NMR, 13C NMR, EI-mass) techniques utilized during characterization revealed the formation of square planar, neutral and 1:2 Pd(II)-hydrazide complexes with the general formula [PdL2Cl2]. In these Pd(II) complexes, the hydrazide ligands are monodentate; the terminal nitrogen is the donor atom. The uncoordinated hydrazide ligands were inactive against both α-glucosidase and carbonic anhydrase II enzymes; however, the respective Pd(II)-hydrazide complexes were approximately 300 times more potent α-glucosidase inhibitors than the standard compound, 1-deoxynojirimycin (DNJ). Some of the Pd(II) complexes also demonstrated potential carbonic anhydrase (CA) inhibition ...
Looking for online definition of carbonic anhydrase inhibitor d's in the Medical Dictionary? carbonic anhydrase inhibitor d's explanation free. What is carbonic anhydrase inhibitor d's? Meaning of carbonic anhydrase inhibitor d's medical term. What does carbonic anhydrase inhibitor d's mean?
TY - JOUR. T1 - Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity. AU - Solesio, María E.. AU - Peixoto, Pablo M.. AU - Debure, Ludovic. AU - Madamba, Stephen M.. AU - de Leon, Mony J.. AU - Wisniewski, Thomas. AU - Pavlov, Evgeny. AU - Fossati, Silvia. PY - 2018/8/1. Y1 - 2018/8/1. N2 - Mounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimers disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid β (Aβ)-mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Aβ, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Aβ, without affecting metabolic function. ATZ was effective at ...
In SS, the proteomic analysis of saliva appears to be a very useful way to assess how the autoimmune disease affects the exocrine function of salivary glands. It is an important tool for identifying biomarkers and posttranslational modifications, as well as for identifying and quantifying peptides, proteins, and neoantigens. A number of proteins have been indicated as pSS biomarkers, showing two- to threefold up- or downregulation at significantly different levels compared with healthy subjects or having an exclusive presence in SS saliva. Proteins of acinar origin (i.e., α-amylase, carbonic anhydrase VI, proline-rich proteins, prolactin-inducible protein precursor) were reduced in patients with pSS, while inflammatory phase proteins, protease inhibitors, and antimicrobial peptides (i.e., lactoferrin, β2-microglobulin, immunoglobulin κ-light chain, calgranulin B, lipocalin 1 precursor, phosphatidylethanolamine binding protein, and defensins) were increased, compared with those in healthy ...
The overall aim of this PhD was to improve our understanding, including the clinical potential, of neonatal Nav1.5 (nNav1.5) expression in human metastatic breast cancer. Mainly, the strongly metastatic MDA-MB-231 cells were used throughout the studies. The specific aims were threefold, as follows: 1) To test the effects of several types of voltage-gated sodium channel (VGSC) blocker on nNav1.5 mRNA and protein expression and metastatic cell behaviours (MCBs); (2) to determine the effects of hypoxia on the drug treatments and MCBs; and (3) to elucidate a possible association of carbonic anhydrase-9 (CA9) and nNav1.5 expression/activity. There are three main Results chapters. Results-1 demonstrates the effects of the drugs on MCBs of MDA-MB-231 cells under normal oxygen level (normoxia). Two classes of blocker were used: a) Local anaesthetics (lidocaine and procaine) and (b) blockers of persistent current (INaP) (ranolazine and riluzole). In addition, a specific VGSC blocker, tetrodotoxin (TTX), ...
• The carbon dioxide gas is temporarily converted to carbonic acid in red blood cells by the enzyme carbonic anhydrase, and then further converted to hydrogen and bicarbonate ions. • The result of increased carbon dioxide is decreased pH causing the Bohr effect. • Elevated carbon dioxide levels enhance unbinding of oxygen from oxyhemoglobin thereby making oxygen available for actively metabolizing cells. • By contrast, decreased carbon dioxide, as in the alveolar spaces, increases affinity of hemoglobin for oxygen and promotes oxygen loading and transport. • To a limited degree, changes in temperature affect the association and dissociation of O2 with hemoglobin. • The oxygen carrying ability of hemoglobin is unaffected by normal temperatures. • Near metabolically active cells, blood temperature rises, increasing the thermal motion of molecules which promotes the unloading of O2 to continue fueling aerobic metabolism in the tissue cells. • When temperature lowers,
Zonisamide causes hyperchloremic, non-anion gap, metabolic acidosis (i.e., decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis) (see PRECAUTIONS, Laboratory Tests subsection). This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of zonisamide on carbonic anhydrase.. Generally, zonisamide-induced metabolic acidosis occurs early in treatment, but it can develop at any time during treatment. Metabolic acidosis generally appears to be dose-dependent and can occur at doses as low as 25 mg daily.. Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, ketogenic diet, or specific drugs) may be additive to the bicarbonate lowering effects of zonisamide.. Some manifestations of acute or chronic metabolic acidosis include hyperventilation, nonspecific symptoms such as fatigue and anorexia, or more severe sequelae including cardiac ...
Acetazolamide-mediated decrease in strong ion difference accounts for the correction of metabolic alkalosis in critically ill patients : Metabolic alkalosis is a commonly encountered acid-base derangement in the intensive care unit. Treatment with the carbonic anhydrase inhibitor acetazolamide is indicated in selected cases. According to the quantitative approach described by Stewart, correction of serum pH due to carbonic anhydrase inhibition in the proximal tubule cannot be explained by excretion of bicarbonate. Using the
3 by the enzyme carbonic anhydrase in the red blood cells.[6] by the reaction CO2 + H2O → H2CO3 → H+ + HCO−. 3. ...
A class of anticonvulsants known as carbonic anhydrase inhibitors (topiramate, zonisamide) are known to increase the risk of ...
Anti-glaucoma: adrenergic agonists, beta-blockers, carbonic anhydrase inhibitors/hyperosmotics, cholinergics, miotics, ...
Carbonic anhydrase inhibitors/. (sulfonamides). *Acetazolamide. *Brinzolamide (+timolol). *Diclofenamide. *Dorzolamide (+ ...
... intermediate to make more CO2 via the enzyme carbonic anhydrase according to the following reaction: H. C. O. 3. −. +. H. +. → ... Circulating hydrogen ions and bicarbonate are shifted through the carbonic acid (H2CO3) ...
"The binding of benzoarylsulfonamide ligands to human carbonic anhydrase is insensitive to formal fluorination of the ligand". ...
Zinc required for several enzymes such as carboxypeptidase, liver alcohol dehydrogenase, carbonic anhydrase ...
Numerous TKIs aiming at various tyrosine kinases have been generated by the originators of these compounds and proven to be effective anti-tumor agents and anti-leukemic agents.[4][5] Based on this work imatinib was developed against chronic myelogenous leukemia (CML)[6] and later gefitinib and erlotinib aiming at the EGF receptor. Sunitinib, an inhibitor of the receptors for FGF, PDGF and VEGF is also based on early studies on TKIs aiming at VEGF receptors.[7] Adavosertib is a Wee1 kinase inhibitor that is undergoing numerous clinical trials in the treatment of refractory solid tumors.[8] However, toxicities such as myelosuppression, diarrhea, and supraventricular tachyarrhythmia have arisen while attempting to determine the toxicity and effectiveness of the drug.[9] Lapatinib, FDA approved for treatment in conjunction with chemotherapy or hormone therapy, is also currently undergoing clinical trials in the treatment of HER2-overexpressing breast cancers as it is suggested intermittent ...
carbonic anhydrase (chloride shift). *oxyhemoglobin. *respiratory quotient. *arterial blood gas. *diffusion capacity (DLCO) ...
Carbonic anhydrase. *Fumarase. *Aconitase. *Enolase *Alpha. *Enolase 2. *Enoyl-CoA hydratase/3-Hydroxyacyl ACP dehydrase ...
"Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with ...
An enzyme, carbonic anhydrase, located within the carboxysome releases CO2 from the dissolved hydrocarbonate ions (HCO−. 3). ... 3 ions are made from CO2 outside the cell by another carbonic anhydrase and are actively pumped into the cell by a membrane ... and within the cytosol they turn back into CO2 very slowly without the help of carbonic anhydrase. This causes the HCO−. 3 ions ... for the biological process of synthesis of complex carbon compounds out of carbonic acid, in the presence of chlorophyll, under ...
Carbonic anhydrase (EC 4.2.1.1). *Tryptophan synthase (EC 4.2.1.20). Category:EC 4.3 (carbon-nitrogen lyases)Edit. *Category:EC ...
The osteoclast releases hydrogen ions through the action of carbonic anhydrase (H2O + CO2 → HCO3− + H+) through the ruffled ... Dysfunction of the carbonic anhydrase has been documented to cause some forms of osteopetrosis. Hydrogen ions are pumped ...
Carbonic anhydrase serves a role in mineralization in sponges, as well as metazoans, implying an ancestral role.[44] Far from ... "Sponge paleogenomics reveals an ancient role for carbonic anhydrase in skeletogenesis". Science. 316 (5833): 1893-1895. Bibcode ...
Band 3 - also assembles various glycolytic enzymes, the presumptive CO2 transporter, and carbonic anhydrase into a ...
The role of cholesterol in the development of cardiovascular disease was elucidated in the second half of the 20th century.[138] This lipid hypothesis prompted attempts to reduce cardiovascular disease burden by lowering cholesterol. Treatment consisted mainly of dietary measures, such as a low-fat diet, and poorly tolerated medicines, such as clofibrate, cholestyramine, and nicotinic acid. Cholesterol researcher Daniel Steinberg writes that while the Coronary Primary Prevention Trial of 1984 demonstrated cholesterol lowering could significantly reduce the risk of heart attacks and angina, physicians, including cardiologists, remained largely unconvinced.[139] Scientists in academic settings and the pharmaceutical industry began trying to develop a drug to reduce cholesterol more effectively. There were several potential targets, with 30 steps in the synthesis of cholesterol from acetyl-coenzyme A.[140] In 1971, Akira Endo, a Japanese biochemist working for the pharmaceutical company Sankyo, ...
Carbonic anhydrase inhibitors/. (sulfonamides). *Acetazolamide. *Brinzolamide (+timolol). *Diclofenamide. *Dorzolamide (+ ...
Within these cells, carbonic anhydrase converts the substances into bicarbonate and hydrogen ions. These are exchanged for ... Changes in the pH of the blood can affect the activity of carbonic anhydrase, and some drugs (such as frusemide, acting on the ... a carbonic anhydrase inhibitor such as acetazolamide, repeated drainage via lumbar puncture, or the insertion of a shunt such ...
Through the enzyme carbonic anhydrase, carbon dioxide reacts with water to give carbonic acid, which decomposes into ...
... which acts by inhibiting the enzyme carbonic anhydrase, and it reduces CSF production by six to 57 percent. It can cause the ...
In carbonic anhydrases, a histidine proton shuttle is utilized to rapidly shuttle protons away from a zinc-bound water molecule ...
"The carbonic anhydrase domain of receptor tyrosine phosphatase beta is a functional ligand for the axonal cell recognition ...
Carbonic anhydrase. 2.6 × 10−2. 4.0 × 105. 1.5 × 107 Fumarase. 5.0 × 10−6. 8.0 × 102. 1.6 × 108 ...
In 1972, it was observed that in the dehydration of H2CO3 catalyzed by carbonic anhydrase, the second-order rate constant ... "H2CO3 as Substrate for Carbonic Anhydrase in the Dehydration of HCO3−". Proceedings of the National Academy of Sciences of the ...
Lutwak-Mann C, Adams CE (April 1957). "Carbonic anhydrase in the female reproductive tract. II. Endometrial carbonic anhydrase ... to possess similar potency to progesterone and hydroxyprogesterone caproate in the rabbit endometrial carbonic anhydrase test, ...
Carbonic anhydrase. *Carboxypeptidase B. *Cardiotrophin 1. (previous page) (next page) Retrieved from "https://en.wikipedia.org ...
A trypsin inhibitor (TI) is a protein and a type of serine protease inhibitor (serpin) that reduces the biological activity of trypsin by controlling the activation and catalytic reactions of proteins.[1] Trypsin is an enzyme involved in the breakdown of many different proteins, primarily as part of digestion in humans and other animals such as monogastrics and young ruminants. When trypsin inhibitor is consumed it acts as an irreversible and competitive substrate.[2] It competes with proteins to bind to trypsin and therefore renders it unavailable to bind with proteins for the digestion process.[1] As a result, protease inhibitors that interfere with digestion activity have an antinutritional effect. Therefore, trypsin inhibitor is considered an anti-nutritional factor or ANF.[3] Additionally, trypsin inhibitor partially interferes with chymotrypsin function. Trypsinogen is an inactive form of trypsin, its inactive form ensures protein aspects of the body, such as the pancreas and muscles, are ...
Aryl sulfonamides are a widely used drug class for the inhibition of carbonic anhydrases. In the context of our program of ... Azobenzene-based inhibitors of human carbonic anhydrase II. In: Beilstein Journal of Organic Chemistry, Vol. 11: pp. 1129-1135 ... interested in the exploration of azobenzene-containing sulfonamides to block the catalytic activity of human carbonic anhydrase ...
We report here the identification of a new T. gondii carbonic anhydrase-related protein (TgCA_RP), which localizes to rhoptries ... A Glycosylphosphatidylinositol-Anchored Carbonic Anhydrase-Related Protein of Toxoplasma gondii Is Important for Rhoptry ... Carbonic anhydrase-related proteins (CARPs) have previously been described as catalytically inactive proteins closely related ... A Glycosylphosphatidylinositol-Anchored Carbonic Anhydrase-Related Protein of Toxoplasma gondii Is Important for Rhoptry ...
The carbonic anhydrase inhibitors act by a noncompetitive, reversible inhibition of the enzyme carbonic anhydrase. This reduces ... This medication, a type of carbonic anhydrase inhibitor, works by lowering pressure in the eye, called aintraocular pressure, ... coma and death have been reported with concomitant use of high-dose aspirin and carbonic anhydrase inhibitors. Precautions: ...
Carbonic Anhydrase. *Phosphorylase. *MAO. *Liver X Receptor. *FAAH. *Acyltransferase. *AhR. *IDO/TDO ...
Carbonic anhydrase I and II as a differentiation marker of human and rat colonic enterocytes. Moreover, compounds 1-12 were ...
... carbonic anhydrase --- MOFs --- carbon capture and storage --- albite --- amorphous --- analcime --- dissolution-precipitation ...
... exchange with carbonic anhydrase immobilized on fiber membranes in artificial lungs Acidic sweep gas with carbonic anhydrase ... FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders The carbonic anhydrase ...
Carbonic Anhydrase Inhibitors (115). *Thiazide Diuretics (1011). *Loop Diuretics (413). *Osmotic Diuretics (74) ...
With simultaneous use of salicylates in high doses with carbonic anhydrase inhibitors can intoxication salicylates.. ...
Carbonic anhydrase inhibitor (0). * Thiazide diuretics (0). *Alpha adrenoceptor blocking drugs (0) ...
carbonic anhydrase 1. 0.059. Dtl. denticleless homolog (Drosophila). 0.058. Aadac. arylacetamide deacetylase (esterase). 0.057 ...
carbonic anhydrase 5a, mitochondrial. 0.017. Adam15. a disintegrin and metallopeptidase domain 15 (metargidin). 0.017. ...
... carbonic anhydrase-1 (CA1); 33, peptidylprolyl isomerase ROC4. ...
Antibodies to rod transducin and carbonic anhydrase II (CAII) have been identified in patients with CAR, MAR and npAIR [5]. ...
Carbonic Anhydrase. *Carboxypeptidase. *Cathepsin. *CETP. *COMT. *Cytochrome P450. *Dihydroorotate Dehydrogenase. *Dipeptidyl ...
... which may be due to carbonic anhydrase inhibition.14 Concomitant use of topiramate with other carbonic anhydrase inhibitors ... It is also a weak carbonic anhydrase inhibitor.11. Topiramate is well absorbed orally with a bioavailability of 80 percent. It ...
Carbonic anhydrase is the enzyme which catalyses the conversion of carbon dioxide and water into carbonate ions. Zinc is the co ... of carbonic anhydrase and any conditions resulting in Zn deficiency can lead to problems associated with egg shell formation. ...
Carbonic Anhydrase. *Carboxypeptidase. *Cathepsin. *COMT. *Cytochrome P450 (CYPs). *Diacylglycerol Lipase (DAGL). *Diglyceride ...
Carbonic Anhydrase. *Carboxypeptidase. *Cathepsin. *CETP. *COMT. *Cytochrome P450. *Dihydroorotate Dehydrogenase. *Dipeptidyl ...
Carbonic Anhydrase Inhibitors. *Diode Cyclophotocoagulation. *Glaucoma Drainage Implants. *iStent® Trabecular Micro-Bypass ...
Oral medications, usually a carbonic anhydrase inhibitor, can help relieve IOP. Other treatments available include laser ...
Carbonic Anhydrase Inhibitors. Visual Field Defect and Retinal Nerve Fiber Layer Defect in a Case of Optic Nerve Head Drusen... ...
... carbonic anhydrase inhibitors and RhoKinase inhibitors. ...
Carbonic Anhydrase Inhibitors. Like beta-blockers, carbonic anhydrase inhibitors decrease the production of aqueous fluid and ...
Update and critical appraisal of combined timolol and carbonic anhydrase inhibitors and the effect on ocular blood flow in ...