Characterization of CA XIII, a Novel Member of the Carbonic Anhydrase Isozyme Family

University of Florence, Florens, Tuscany, Italy
Journal of Biological Chemistry (Impact Factor: 4.6). 02/2004; 279(4):2719-27. DOI: 10.1074/jbc.M308984200
Source: PubMed

ABSTRACT The carbonic anhydrase (CA) gene family has been reported to consist of at least 11 enzymatically active members and a few inactive homologous proteins. Recent analyses of human and mouse databases provided evidence that human and mouse genomes contain genes for still another novel CA isozyme hereby named CA XIII. In the present study, we modeled the structure of human CA XIII. This model revealed a globular molecule with high structural similarity to cytosolic isozymes, CA I, II, and III. Recombinant mouse CA XIII showed catalytic activity similar to those of mitochondrial CA V and cytosolic CA I, with k(cat)/K(m) of 4.3 x 10(7) m(-1) s(-1), and k(cat) of 8.3 x 10(4) s(-1). It is very susceptible to inhibition by sulfonamide and anionic inhibitors, with inhibition constants of 17 nm for acetazolamide, a clinically used sulfonamide, and of 0.25 microm, for cyanate, respectively. Using panels of cDNAs we evaluated human and mouse CA13 gene expression in a number of different tissues. In human tissues, positive signals were identified in the thymus, small intestine, spleen, prostate, ovary, colon, and testis. In mouse, positive tissues included the spleen, lung, kidney, heart, brain, skeletal muscle, and testis. We also investigated the cellular and subcellular localization of CA XIII in human and mouse tissues using an antibody raised against a polypeptide of 14 amino acids common for both human and mouse orthologues. Immunohistochemical staining showed a unique and widespread distribution pattern for CA XIII compared with the other cytosolic CA isozymes. In conclusion, the predicted amino acid sequence, structural model, distribution, and activity data suggest that CA XIII represents a novel enzyme, which may play important physiological roles in several organs.

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    ABSTRACT: With 12 different isozymes, Carbonic anhydrase plays a key role in acid-base balance, CO2 and ion transport…etc. Any change in the enzymatic activity may cause disturbances in these processes leading to different disorders. The study focuses on the association of electromorphs of Carbonic anhydrase-II (CAII) with peptic ulcers and ulcerated cancers, which result due to an imbalance between the aggressive and defensive factors necessary for maintaining the pH of the gastric lumen. Endoscopically confirmed 210 duodenal ulcer, 50 gastric ulcer and 50 gastric cancer cases were considered along with 110 healthy individuals for comparative study. Since H.pylori infection is considered as primary risk factor, Rapid Urease Test (RUT) was performed to identify the infection status in both disease and control groups. Phenotyping of CAII was carried out in both control and disease by subjecting the haemolysate to PAGE and detecting the bands based on esterase activity of CAII using α or β-napthol acetate. Frequency distribution of different phenotypes with respect to various factors was compiled and relative risk estimates were obtained using Woolf’s δ-method.The allelic frequencies of CAII calculated, were tested for Hardy-Weinberg equilibrium. Frequency distribution of CAII phenotypes showed increased number of heterozygotes (2-1) in controls, against higher number of homozygotes (2-2) in diseased group. Similarly, blood group O was predominant in disease group as against group B in controls. Most of the controls were negative for H.pylori infection and almost 100% individuals in disease group were positive. In conclusion, the allele CAII2 was found to be associated with peptic ulcers and ulcerated cancers along with blood group O and positive H.pylori infectivity status, predisposing an individual to the disease condition.
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    ABSTRACT: Carbonic anhydrase II is present in normal gastric mucosa; thus, this study aimed to investigate whether its expression persisted in neoplastic gastric tissues, as well as its prognostic value for gastric cancer patients.
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