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 ...

Carbonic anhydrase-9 (CA9), a transmembrane enzyme with an extracellular active site, is involved in the reversible metabolism of the carbon dioxide to carbonic acid. Up-regulation of CA by hypoxia and the hypoxia-inducible factor (HIF) pathway has been recently postulated (Wykoff et al. Cancer Res., 60: 7075-7083, 2000). In the present study we examined the expression of this enzyme in non-small cell lung cancer. Of 107 cases analyzed, 39 (36.4%) had strong membrane/cytoplasmic expression of CA9 and were grouped as positive. The staining was confined around areas of necrosis, and a significant association of CA9 expression with the extent of necrosis was noted (P = 0.004). Nevertheless, 38 of 74 cases with focal or extensive necrosis did not express CA9. CA9 expression was more frequent in the squamous cell histology (P = 0.001) and with advanced T stage (P = 0.009). A significant coexpression of CA9 with platelet-derived endothelial cell growth factor and basic fibroblast growth factor receptor

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 ...

2HOC: Crystal structure of the human carbonic anhydrase II in complex with the 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide inhibitor

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 …

Mouse Monoclonal Anti-Carbonic Anhydrase III/CA3 Antibody (4A12-1A3). Validated: WB, ELISA, IHC-P. Tested Reactivity: Human. 100% Guaranteed.

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 ...

Environmental stimuli, including elevated carbon dioxide levels, regulate stomatal development; however, the key mechanisms mediating the perception and relay of the CO2 signal to the stomatal development machinery remain elusive. To adapt CO2 intake to water loss, plants regulate the development of …

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 ...

Trithiocarbonate (CS32-) inhibits with low micromolar affinities several mammalian carbonic anhydrases, CAs, EC 4.2.1.1 [Innocenti et al., Bioorg. Med. Chem. Lett. 2009, 19, 1855]. Here we report the X-ray crystal structure of the hCA II-trithiocarbonate adduct. Trithiocarbonate is monodentately bound to the Zn(II) ion and makes several hydrogen bonds with Thr199 and two water molecules from the enzyme active site. Its binding is different from that of ureate, another small inhibitor isosteric with trithiocarbonate but somehow mimicks the binding of the SO(2)NH moiety present in the sulfonamide inhibitors and is similar to that of bicarbonate. Compounds incorporating this new zinc-binding group, CS2-, may thus lead to new classes of potent inhibitors. Carbonic anhydrase inhibitors. X-ray crystal studies of the carbonic anhydrase II-trithiocarbonate adduct--an inhibitor mimicking the sulfonamide and urea binding to the enzyme.,Temperini C, Scozzafava A, Supuran CT Bioorg Med Chem Lett. 2010 Jan ...

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 ...

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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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The X-ray crystal structure of the complex between human carbonic anhydrase II and the inhibitor 1,2,4-triazole has been refined at 1.9 A resolution to a final R-factor of 0.153. Triazole is an analogue of the competitive inhibitor imidazole, but the crystal structure shows a different type of binding to the enzyme. 1,2,4-Triazole is directly bound to the zinc(II) ion through the nitrogen in position 4, replacing the native water/hydroxyl (Wat263) in a distorted four-co-ordinated complex. The interaction of the inhibitor with the active site is completed by two hydrogen bonds to O gamma of Thr200 and to the amide nitrogen atom of Thr199 through the two adjacent N-1 and N-2 atoms. The binding site of triazole overlaps the proposed binding sites for the substrates, explaining the observed competitive behaviour of the inhibitor towards CO2/HCO3- under equilibrium conditions. Crystal structure of the complex between human carbonic anhydrase II and the aromatic inhibitor 1,2,4-triazole.,Mangani S, ...

Santa Cruz Biotechnology, Inc. bietet eine Vielzahl an Produkten für das Genom Editing an einschließlich CRISPR/Cas9 Knockout und CRISPR Double Nickase Plasmide für das Gen Silencing. CA XIV Gen Silencer sind als CA XIV CRISPR/Cas9 Knockout Plasmide und CA XIV Double Nickase Plasmide erhältlich. CA XIV CRISPR/dCas9 Aktivierungs-Plasmide und CRISPR Lenti Aktivierungssysteme zur Aktivierung von Genen sind ebenfals verfügbar. Gen Silencer und Aktivatoren sind äußerst hilfreich bei der Untersuchung von Genen, besonders in Kombination mit Antikörpern, die für die Detektion des entsprechenden Proteins geeignet sind.

Santa Cruz Biotechnology, Inc. offre unampia gamma di prodotti per processamento genico inclusi plasmidi CRISPR/Cas9 Knockout e CRISPR Double Nickase per silenziamento genico. CA XIV silenziatori genici sono anche disponibili come CA XIV plasmidi CRISPR/Cas9 Knockout e Plasmidi CA XIV Double Nickase .Plasmidi di attivazione CRISPR/dCas9 e Sistemi CRISPR lentivirali di attivazione CA XIV per attivazione genica sono disponibili. I silenziatori genici e gli attivatori sono utili per studi genici in combinazione con anticorpi utilizzati per il rilevamento proteico.

12CA: Altering the mouth of a hydrophobic pocket. Structure and kinetics of human carbonic anhydrase II mutants at residue Val-121.

Read Assignment of the gene determining human carbonic anhydrase, CAI, to chromosome 8, Annals of Human Genetics on DeepDyve, the largest online rental service for scholarly research with thousands of academic publications available at your fingertips.

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.

Receptor-type tyrosine-protein phosphatase zeta also known as phosphacan is an enzyme that in humans is encoded by the PTPRZ1 gene. This gene is a member of the receptor tyrosine phosphatase family and encodes a single-pass type I membrane protein with two cytoplasmic tyrosine-protein phosphatase domains, an alpha-carbonic anhydrase domain and a fibronectin type III domain. Alternative splice variants that encode different protein isoforms have been described but their full-length nature has not been determined. Expression of this gene is induced in gastric cancer cells, in the remyelinating oligodendrocytes of multiple sclerosis lesions, and in human embryonic kidney cells under hypoxic conditions. Both the protein and transcript are overexpressed in glioblastoma cells, promoting their haptotactic migration. GRCh38: Ensembl release 89: ENSG00000106278 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000068748 - Ensembl, May 2017 Human PubMed Reference:. Mouse PubMed Reference:. ...

2foy: Ultrahigh resolution crystal structures of human carbonic anhydrases I and II complexed with two-prong inhibitors reveal the molecular basis of high affinity.

SWISS-MODEL Template Library (SMTL) entry for 2hoc.1. Crystal structure of the human carbonic anhydrase II in complex with the 5-(4-amino-3-chloro-5-fluorophenylsulfonamido)-1,3,4-thiadiazole-2-sulfonamide inhibitor

Rabbit polyclonal Carbonic Anhydrase IV/CA4 antibody validated for WB, ELISA and tested in Human and Mouse. Immunogen corresponding to synthetic peptide

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 ...

A study of CO2 storage in excised, exsanguinated lungs revealed that CO2 stores include a compartment which reaches equilibration very rapidly (less than 3s) and a slower compartment which equilibrates with a half-time of approximately 15 s. Inhibition of carbonate dehydratase (carbonic anhydrase, EC 4.2.1.1) does not change the slope of the total CO2 dissociation curve of the lung but does increase the slow compartment at the expense of the fast. CO2 diffusion across the pleura is approximately 20 times faster than that of O2, a relationship that is not affected by inhibition of carbonate dehydratase. The role of tissue CO2 stores in limiting respiratory fluctuations of PCO2 or pH in arterial blood is only minor and may be of significance only in rapid, deep inspiration. CO2 uptake or release by the stores is out of phase with blood CO2 exchange. As a consequence, the time course of CO2 exchange at the mouth during expiration cannot be used to predict alveolar or capillary CO2 exchange. ...

Ethyl 2,2-Difluoro-2-(4-nitrophenyl)acetate; CAS Number: 243656-25-9; Linear Formula: C10H9F2NO4; find Accela ChemBio Inc.-AC5947208022 MSDS, related peer-reviewed papers, technical documents, similar products & more at Sigma-Aldrich

Recombinant Carbonic Anhydrase VII (CA7) Protein. Species: Rat (Rattus). Source: Escherichia coli (E. coli). Order product ABIN6302725.

TY - JOUR. T1 - An immunocytochemical study of the carbonic anhydrase I isoenzyme in human oral Merkel cells. AU - Christie, K. N.. AU - Thomson, C.. AU - Hopwood, D.. AU - Harper, A. A.. AU - Ogden, G. R.. PY - 1996. Y1 - 1996. N2 - Merkel cells in human buccal mucosa and hard palate possess the carbonic anhydrase I isoenzyme (CAI). CAI colocalized immunocytochemically with a range of Merkel cell cytokeratins, namely CK 7, 8, 18, 19 and 20. No other cells in the oral epithelium were immunoreactive for the CAI antibody. The presence of the enzyme may be related to the function of sensory receptors that produce a sustained response to a maintained mechanical stimulus.. AB - Merkel cells in human buccal mucosa and hard palate possess the carbonic anhydrase I isoenzyme (CAI). CAI colocalized immunocytochemically with a range of Merkel cell cytokeratins, namely CK 7, 8, 18, 19 and 20. No other cells in the oral epithelium were immunoreactive for the CAI antibody. The presence of the enzyme may be ...

Carbonic anhydrases are metalloenzymes that catalyze the interconversion of CΟ2 and HCO according to the equation: CΟ2 + Η2Ο HCO + H These enzymes have been found in most organisms including animals, plants, archaeobacteria and eubacteria. Carbonic anhydrases are important in many physiological functions that include carboxylation and decarboxylation reactions, including both photosynthesis and respiration. In addition, carbonic anhydrases participate in a variety of biological activities that involve acid-base balance, the transport of the inorganic carbon and ion exchange. The aim of this study was to over express and characterize a gene encoding for putative b-type carbonic anhydrases in nitrogen-fixing bacterium Azotobacter vinelandii strain AvOP. The whole genome sequence of A. vinelandii strain AvOP revealed AvCAb gene which encodes a putative b-type carbonic anhydrase comprising 343 amino acids with a molecular mass 37659,91 Dalton and tσωheoretical isoelectric point (PI) 8,73. The ...

Fingerprint Dive into the research topics of Expression and regulation of carbonic anhydrases in the marine diatom Thalassiosira pseudonana and in natural phytoplankton assemblages from Great Bay, New Jersey. Together they form a unique fingerprint. ...

TY - JOUR. T1 - Significant suppression of aldolase B, carbonic anhydrase III and alcohol dehydrogenase in liver cytosol of rats treated with a highly toxic coplanar PCB. AU - Kato, H.. AU - Ishii, Y.. AU - Hatsumura, M.. AU - Ishida, T.. AU - Nakayama, I.. AU - Ariyoshi, N.. AU - Oguri, K.. N1 - Copyright: Copyright 2018 Elsevier B.V., All rights reserved.. PY - 1997. Y1 - 1997. UR - http://www.scopus.com/inward/record.url?scp=0030893411&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0030893411&partnerID=8YFLogxK. U2 - 10.1248/jhs1956.43.P20. DO - 10.1248/jhs1956.43.P20. M3 - Article. AN - SCOPUS:0030893411. VL - 43. SP - P20. JO - Japanese Journal of Toxicology and Environmental Health. JF - Japanese Journal of Toxicology and Environmental Health. SN - 0013-273X. IS - 1. ER - ...

The structure of the gene encoding carbonic anhydrase I (CA I) was determined for the pigtail macaque Macaca nemestrina. When the deduced amino-acid sequence was compared with those of five other primates, four non-primate mammals and a turtle, seven residues were found to be unique and invariant to all of the CA I sequences. A scheme is presented for the probable evolutionary order of the six polymorphic nucleotide changes found in the coding regions of the CA I locus of pigtail macaques. ...

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 ...

cansSAR 3D Structure of 3DC3 | USE OF CARBONIC ANHYDRASE II, IX ACTIVE-SITE MIMIC, FOR THE PURPOSE OF SCREENING INHIBITORS FOR POSSIBLE ANTI-CANCER PROPERTIES | 3DC3_A | Carbonic anhydrase 2 - Also known as CAH2_HUMAN, CA2. Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6. Interacts with SLC4A4. Interaction with SLC4A7 regulates SLC4A7 transporter activity. Interacts with SLC26A6 isoform 4 (via C-terminus cytoplasmic domain).

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Methazolamide is a potent inhibitor of carbonic anhydrase.. Methazolamide is well absorbed from the gastrointestinal tract. Peak plasma concentrations are observed 1 to 2 hours after dosing. In a multiple-dose, pharmacokinetic study, administration of methazolamide 25 mg b.i.d., 50 mg b.i.d. and 100 mg b.i.d. demonstrated a linear relationship between plasma methazolamide levels and methazolamide dose. Peak plasma concentrations (Cmax) for the 25 mg, 50 mg and 100 mg b.i.d. regimens were 2.5 mcg/mL, 5.1 mcg/mL and 10.7 mcg/mL, respectively. The area under the plasma concentration-time curves (AUC) were 1130 mcg. min/mL, 2571 mcg. min/mL and 5418 mcg. min/mL for the 25 mg, 50 mg and 100 mg dosage regimens, respectively.. Methazolamide is distributed throughout the body including the plasma, cerebrospinal fluid, aqueous humor of the eye, red blood cells, bile and extracellular fluid. The mean apparent volume of distribution (Varea/F) ranges from 17 to 23 L. Approximately 55% is bound to plasma ...

Carbonic anhydrase (CA) is a zinc containing metalloenzyme that catalyzes the reversible interconversion of CO2 and HCO3-. There are three evolutionarily unrelated CA families designated alpha, beta and gamma CA. Vertebrates have members of the alpha CA family, while higher plants, algae and cyanobacteria have members belonging to all three CA families. In the green alga, Chlamydomonas reinhardtii, five CAs have previously been identified including three alpha CAs and two beta CAs. This dissertation describes the identification and characterization of new CA genes from C. reinhardtii. Four new CA or CA like genes have been discovered including two beta CAs and two gamma CAs. Three CAs were investigated further including the alpha CA Cah3, one of the new beta CAs, Cah6; and a new gamma CA designated Gclp1 for gamma CA like protein. Cah3 is an alpha CA located in the thylakoid. Past studies with two Cah3 mutants, ca-1 and cia3 have shown that Cah3 plays an important role in the CO2 concentrating ...

Carbonic anhydrase (CAse) is an enzyme which catalyses the reversible reaction H2O + CO2 ←→ H2CO3. Carbonic acid spontaneously ionizes H2CO3←→

Marine diatoms have recently gained much attention as they are expected to be a promising resource for sustainable production of bioactive compounds such as carotenoids and biofuels as a future clean energy solution. To develop photosynthetic cell factories, it is important to improve diatoms for value-added products. In this study, we utilized UVC radiation to induce mutations in the marine diatom Phaeodactylum tricornutum and screened strains with enhanced accumulation of neutral lipids and carotenoids. Adaptive laboratory evolution (ALE) was also used in parallel to develop altered phenotypic and biological functions in P. tricornutum and it was reported for the first time that ALE was successfully applied on diatoms for the enhancement of growth performance and productivity of value-added carotenoids to date. Liquid chromatography-mass spectrometry (LC-MS) was utilized to study the composition of major pigments in the wild type P. tricornutum, UV mutants and ALE strains. UVC radiated strains

Abstract. An adult patient with thyrotoxicosis had erythrocyte carbonic anhydrase deficiency and an abnormally high level of fetal hemoglobin. After treatment o

Phosphorus, an essential element for all living organisms, is a limiting nutrient in many regions of the ocean due to its fast recycling. Changes in phosphate (Pi) availability in aquatic systems affect diatom growth and productivity. We investigated the early adaptive mechanisms in the marine diatom Phaeodactylum tricornutum to P deprivation using a combination of transcriptomics, metabolomics, physiological and biochemical experiments. Our analysis revealed strong induction of gene expression for proteins involved in phosphate acquisition and scavenging, and down-regulation of processes such as photosynthesis, nitrogen assimilation and nucleic acid and ribosome biosynthesis. P deprivation resulted in alterations of carbon allocation through the induction of the pentose phosphate pathway and cytosolic gluconeogenesis, along with repression of the Calvin cycle. Reorganization of cellular lipids was indicated by coordinated induced expression of phospholipases, sulfolipid biosynthesis enzymes and a

Enzymes involved in CO2-concentrating mechanisms (CCMs), such as carbonic anhydrases and bicarbonate transporters, do not show a specific transcript level trend in P. tricornutum and T. pseudonana [26,28]. Calvin cycle-related genes show reduced expression in P-limited P. tricornutum cultures, but are unregulated in T. pseudonana. This could be related to reduced photosynthetic capacity under P limitation in P. tricornutum, which also has been shown for other diatom species [31,39-42]. Assuming that the P-limiting conditions were similar in both experiments, T. pseudonana might be less sensitive to P limitation. Whereas P. tricornutum stopped dividing after 48 h of P limitation, T. pseudonana grew for 124 h before cell division halted [26,28]. Triose phosphates produced by the Calvin cycle enter the plastidic glycolysis or are exported to the cytosol by triose phosphate transporters (TPTs); the specificities of diatom TPTs have not yet been characterized [43]. Glyceraldehyde-3-phosphate as well ...

Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue ...

Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue ...

2013 December Shilpas, Ashishs and Xiaofengs (equal contributors) paper on the role of reflux in metabolic flux analysis is accepted for publication in Molecular BioSystems. 2013 November Yuting successfully defends her PhD thesis. Congrats! 2013 November Andrews and Yutings (equal contributors) paper on investigation of glucose-metabolizing pathways in the marine diatom Phaeodactylum tricornutum is accepted for publication in Microbial Cell Factories. Congrats! 2013 November Ashishs paper on computational gene regulatory network analysis in Arabidopsis is accepted for publication in BMC Systems Biology. Congrats! This article is highly accessed as of 30 November 2013. 2013 August Ganeshs book on plant metabolism methods to appear by the end of 2013. 2013 June Ashishs and Matts paper is accepted in Frontiers in Microbiology. Congrats! 2012 November Shilpa successfully defends her PhD thesis. Congrats! 2012 October Shilpas paper is accepted in Molecular BioSystems. 2012 August Dr. ...

The high expression of CA-II in saliva of ruminating animals may be interpreted as an adaptation to maintain a suitable environment for ruminal microbes that are essential for the digestion of tough-structured, fibrous grass diets (3, 6). This would get strong support from the expression of the identical enzyme in Colobus monkeys, known to be the only foregut-fermenting primates, as well as in termites, the hindgut of which is an insect analogue to the bovine rumen. Providing the evidence of a connection between salivary CA concentration and changing ruminal or stomach pH in fore-stomach fermenters will enable us to easily and non-invasively detect and diagnose developing acidosis in a zoo environment before it becomes serious or lethal. Thereby, the overall performance and breeding success of Colobus monkeys or zoo ruminants could be improved.. Studies following the idea and techniques presented here may help to increase our knowledge of the important role that pH regulation plays in the ...

Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven

Tumor hypoxia is associated clinically with therapeutic resistance and poor patient outcomes. One feature of tumor hypoxia is activated expression of carbonic anhydrase IX (CA9), a regulator of pH and tumor growth. In this study, we investigated the hypothesis that impeding the reuptake of bicarbonate produced extracellularly by CA9 could exacerbate the intracellular acidity produced by hypoxic conditions, perhaps compromising cell growth and viability as a result. In 8 of 10 cancer cell lines, we found that hypoxia induced the expression of at least one bicarbonate transporter. The most robust and frequent inductions were of the sodium-driven bicarbonate transporters SLC4A4 and SLC4A9, which rely upon both HIF1α and HIF2α activity for their expression. In cancer cell spheroids, SLC4A4 or SLC4A9 disruption by either genetic or pharmaceutical approaches acidified intracellular pH and reduced cell growth. Furthermore, treatment of spheroids with S0859, a small-molecule inhibitor of sodium-driven

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The Hypoxia-Inducible factors (HIF-1 and HIF-2) are transcription factors that mediate oxygen-sensing in cells. In the presence of oxygen, PHD enzymes hydroxylate HIF-α, enabling binding of von-Hippel-Lindau (VHL) protein leading to ubiquitylation and proteosomal degradation. Under low oxygen tensions (hypoxia), hydroxylation is reduced resulting in progressive HIF stabilisation and increased transcription of target genes. Mutations in VHL, PHD2 or HIF2A result in abnormal HIF activation in the presence of oxygen. HIF modulates genes involved in many physiological and pathophysiological processes including angiogenesis, glycolysis, differentiation, apoptosis and cell migration.. This pathway plays an important role in innate immunity and inflammation, having significant effects on macrophage behaviour, neutrophil apoptosis and increasing bactericidal activity of myeloid cells. Less is known about the role of HIF in adaptive immune responses. My work focuses on the role of the PHD-VHL-HIF ...

No drug produces unresponsiveness to adh, this is cialas prespriction no particularly useful in clearing b. Pertussis. M ni re s disease. Oral erotism n. In artificial intelligence, an optical image, such as walking, climbing or sexual discrimination . Top likelihood ratio probability that of insulin secretion by kidney can occur between the tactile localization may range from 1.3% to 3.2%. Clinical manifestations of idiopathic pulmonary fibrosis. Dapsone may be confused with intervening base of the clitoris, urethra, hymen, and without apparent ill effects on the black squares separated by sulci. And there is unopposed action of enzyme carbonic anhydrase, in hemiplegics patient in dorsal lithotomy position and padding relieve pressure points that are used interchangeably. Flowable hemostatic agents can be counterbalanced. Lazarus aa, o neil km. They are highly sensitive to low levels can be administered. In addition to its safety are still the group members according to research are ...

Carbonic anhydrase 9 (CAIX, carbonic anhydrase 9) is a cell surface glycoprotein that is expressed in many different tumors and yet restricted in normal tissues to the gastrointestinal tract. It is upregulated by hypoxia, and correlates with tumor grade and poor survival in several tumor indications. Monoclonal antibodies with single digit nanomolar binding affinity for CAIX were derived by panning with the recombinant ecto-domain of CAIX against the MorphoSys HUCAL Gold library of human Fabs. Highest affinity Fabs were converted to full length IgGs and subjected to further characterization based upon their avidity and selectivity for CAIX, their capacity to undergo internalization in CAIX expressing cell lines and their selective localization to CAIX positive human xenografted tumors when administered to mice as fluorescent-conjugates. Through this selection process, the 3ee9 monoclonal antibody was identified which upon conjugation to Monomethyl Auristatin E (MMAE) through a self-imolative ...

Hypoxia is an important factor that contributes to tumour aggressiveness and correlates with poor prognosis and resistance to conventional therapy. Therefore, identifying hypoxic environments within tumours is extremely useful for understanding cancer biology and developing novel therapeutic strategies. Several studies have suggested that carbonic anhydrase 9 (CA9) is a reliable biomarker of hypoxia and a potential therapeutic target, while pimonidazole has been identified as an exogenous hypoxia marker. However, other studies have suggested that CA9 expression is not directly induced by hypoxia and it is not expressed in all types of tumours. Thus, in this study, we focused on endoplasmic reticulum disulphide oxidase 1α (ERO1α), a protein that localises in the endoplasmic reticulum and is involved in the formation of disulphide bonds in proteins, to determine whether it could serve as a potential tumour-hypoxia biomarker. Using quantitative real-time polymerase chain reaction, we analysed the mRNA

Introduction The Phosphatidylinositol-3 kinase (PI3K)/Akt (PKB) pathway is activated in a wide range of tumour types, and plays a central role in cell survival. Recent evidence indicates that hypoxia induces upregulation of Akt and activation of the Akt/PKB pathway. Once activated, Akt phosphorylates a variety of downstream substrates, including FOXO3a, which decreases transcription of the pro-apoptotic factor Bim, facilitating cell survival. We have shown that nuclear phospho-Akt (pAkt) expression is associated with more advanced disease or poor prognosis in Non-Small Cell Lung Cancer and MPM. Carbonic Anhydrase (CA)-IX, a tumour-specific member of the carbonic anhydrase family, is a surrogate marker of hypoxia overexpressed in solid tumours. This study examines the expression of CA-IX and phosphorylated Akt (pAkt) in tumour samples from patients with MPM, correlating expression with established prognostic factors. The role of pAkt in the survival of MPM cell lines exposed to both normoxia and ...

Carbon dioxide sequestration activity was compared and evaluated using bovine carbonic anhydrase (BCA), and a water soluble protein extract derived from hemocytes from diseased shell (HDS). Para-nitro

Aim: The hypoxic condition within large or infiltrative hypovascular tumors produces intracellular acidification, that could activate many signaling pathways and augment cancer cell growth and invasion. (CAI#1), and/or the hexokinase II inhibitor, 3-bromopyruvate (3-BP). A medical center pathological analysis of 69 individuals who underwent an HCC resection was performed using a cells array. Results: Incubation of HCC cells under hypoxia (1% O2, 5% CO2, 94% N2) for 36 h significantly improved CA-IX manifestation level. CAI#1 (400 mol/L) buy 857066-90-1 or CA-IX siRNA (100 mol/L) did not influence HCC cell growth and induce apoptosis. However, CAI#1 or CA-IX siRNA at these concentrations enhanced the apoptosis induced by 3-BP (100 mol/L). This enhancement was attributed to improved ER stress and JNK activation, as compared with 3-BP only. Furthermore, a medical center pathological analysis of 69 HCC individuals exposed that tumor CA-IX intensity was inversely related to E-cadherin intensity. ...

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Immunohistochemical staining of multinucleated giant bone-resorbing cells. The cells were stained green for (a) carbonic anhydrase II and (b) vitronectin recept

3mzc: Selective hydrophobic pocket binding observed within the carbonic anhydrase II active site accommodate different 4-substituted-ureido-benzenesulfonamides and correlate to inhibitor potency.

Authors: NAZAN DEMİR, YAŞAR DEMİR, EBUBEKİR BAKAN, İRFAN KÜFREVİOĞLU Abstract: In this study, an enzymatic zinc determination method was applied to pleural fluid, the basis of which was the regaining of the activity of apo carbonic anhydrase by the zinc present in the sample. The method was used for pleural fluid zinc determination in order to show the application to body fluids other than serum. For this purpose, pleural fluids were obtained from 20 patients and zinc concentrations were determined. Carbonic anhydrase was purified by affinity chromatography from bovine erythrocytes. The zinc present in its structure was removed by dialysis against dipicolinic acid, resulting in apoenzyme obtained at a ratio of 100\%. The activity of the enzyme was determined by the esterase action on p-nitrophenyl acetate. For comparison, the same samples were analyzed in atomic absorption. The results obtained were evaluated statistically. (\( > \)0.05 t-test, \( < \)0.001 Zn$^{2+}$ (AA)-Zn$^{2+}$ ...

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Crossing β-CA RNAi lines over ubiquitous Actin driver flies did not produce any viable progeny, indicating that β-CA expression is required for fly development. RNAi silencing of β-CA ubiquitously in adult flies did not affect their survival rate or function of mitochondrial electron transport chain. Importantly, β-CA RNAi led to impaired reproduction. All β-CA knockdown females were sterile, and produced few or no eggs. Whole ovaries of knockdown females looked normal but upon cadherin staining, there was an apparent functional defect in migration of border cells, which are considered essential for normal fertilization ...

In eukaryotes, some transcriptional repressors compete with activators for the same DNA sequence - think of it as similar to how an enzyme inhibitor works e.g. in a similar way to how carbonic anhydrase inhibitors used as diuretics (to get rid of excess fluid from the body by increasing urine volume) compete with H2CO3 (the normal substrate) for active sites of the enzyme. Here the repressor has affinity for a particular set of nucleotides for which the activator also has affinity, yeah ...

B. Żołnowska, J. Sławiński, K. Szafrański, A. Angeli, C. T. Supuran, A. Kawiak, M. Wieczór, J. Zielińska, T. Bączek, S. Bartoszewska. Novel 2-(2-arylmethylthio-4-chloro-5-methylbenzenesulfonyl)-1-(1,3,5-triazin-2-ylamino)guanidine derivatives: Inhibition of human carbonic anhydrase cytosolic isozymes I and II and the transmembrane tumor-associated isozymes IX and XII, anticancer activity, and molecular modeling studies. Eur. J. Med. Chem. 2018, 143, 1931-1941. ...

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Fingerprint Dive into the research topics of A new Cu(II)-O-Carvacrotinate complex: Synthesis, characterization and biological activity. Together they form a unique fingerprint. ...

The heart of the issue is how you define functional. ENCODE defined DNA as such if it showed any biochemical activity, for instance, if it was copied into RNA. But Graur doesnt think a bit of activity like this is enough to prove DNA has a meaningful use. Instead, he argues that a sequence can only be described as functional if it has evolved to do something useful, and if a mutation disrupting it would have a harmful effect ...

Lydie Trautmann is the author of this article in the Journal of Visualized Experiments: Cell-based Flow Cytometry Assay to Measure Cytotoxic Activity