Carbonic anhydrase distribution

Lutjen-DrecollE, Lonnerholm G, Eichhorn M. Carbonic anhydrase distribution in the human and monkey eye by light microscopy. Graefes Arch Clin Exp Ophthalmol 1983 220 285-291. 

Zinc. The 2—3 g of zinc in the human body are widely distributed in every tissue and tissue duid (90—92). About 90 wt % is in muscle and bone unusually high concentrations are in the choroid of the eye and in the prostate gland (93). Almost all of the zinc in the blood is associated with carbonic anhydrase in the erythrocytes (94). Zinc is concentrated in nucleic acids (90), and found in the nuclear, mitochondrial, and supernatant fractions of all cells. 

Carbonic anhydrase was the first Zn metallo-enzyme to be discovered (1940) and in its several forms is widely distributed in plants and animals. It catalyses the equilibrium reaction ... 

Graham D, Reed ML, Patterson BD, Hockley DG. 1984. Chemical properties, distribution, and physiology of plant and algal carbonic anhydrase. Annals of the New York Academy of Science 429 222-237. 

Chronic in vivo hemolysis produces serum lactic dehydrogenase elevations in patients with mitral or atrial valve cardiac prosthesis (J2). In a series of 11 such patients these increases ranged from 1.1 to 1.6 times the upper limit of normal (S29). Blood pH is altered in hemolyzcd specimens because carbonic anhydrase is liberated from the erythrocytes and presumably alters the distribution of H2CO3 and NaHCOs (B2). Hemolysis will effect acid phosphatase activity if the substrate is hydrolyzed by erythrocyte acid phosphatase. Thus, hemolysis would be of concern if phenyl phosphate was the substrate, but would have a negligible effect if )8-glycerophosphate, which is not hydrolyzed by red cell acid phosphatase, was used (Bl). 

There are several types of -class CAs i.e., a-CA I-VII, reported in the literature, out of which the human carbonic anhydrase II (HCA II), the most extensively studied carbonic anhydrase, has an exceptionally high CO2 hydration rate and a wide tissue distribution 107). The HCA II comprises a single polypeptide chain with a molecular mass of 29.3 kDa and contains one catalytic zinc ion, coordinated to three histidine residues, His 94, His 96, and His 119. A tetrahedral coordination geometry around the metal center is completed with a water molecule, which forms a hydroxide ion with a pK value of 7.0 108). Quigley and co-workers 109,110) reported that the inhibition of the synthesis of HCO3 from CO2 and OH- reduces aqueous humor formation and lowers intra-ocular pressure, which is a major risk factor for primary open-angle glaucoma. 

Bernstein, R. S., Nevalaincn, J., Schraer, F., Schraer, H. Intracellular distribution and role of carbonic anhydrase in the avian (Gattus domesticus) shell gland mucosa. Biochim. Biophys. Acta 159, 367 (1968)... 

Lutwak-Mann, C. Carbonic anhydrase in the female reproductive tract. Occurence, distribution and hormonal dependence. J. Endocrin. 13, 26 (1955)... 

Carter, M. J. Carbonic anhydrase isoenzymes properties distribution and functional significance. BioL Rev. 47, 465 (1972)... 

Another simple addition reaction is the hydration of C02 to form the bicarbonate ion. Without catalysis the reaction may require several seconds,4 5 the apparent first-order rate constant being -0.03 s 1 at 25°C. Cells must often hasten die process. The specific catalyst carbonic anhydrase is widespread in its distribution... 

Isoenzymes III and VII have a more specialized distribution. Carbonic anhydrase III is abundant in adipocytes which use bicarbonate in fatty acid synthesis.7 Isoenzyme V is present in the mitochondrial matrix and is also abundant in both adipocytes and liver.7 8 Isoenzyme IV is a larger membrane-associated form, while VI is secreted into the saliva.10 Carbonic anhydrase has also been identified in E. coli.,11 in a methanobacterium,12 and in green plants.13 133 A 60-kDa carbonic anhydrase called nacrein is found in the organic matrix of the nacreous layer of the pearl oyster, the layer that forms aragonite (orthorhombic calcium carbonate) in the shell and in pearls.14... 

Supuran, C.T. Carbonic anhydrases catalytic and inhibition mechanism, distribution and physiological roles. In Carbonic Anhydrase Its Inhibitors and Activators, ed. Supuran, C.T., Scozzafava, A., Conway, J., CRC Press Boca Raton, FL, 2004, pp. 1-24. 

Fig. 5-20. Proposal for the hydration-dehydration mechanism of carbonic anhydrase. The pK of the zinc bound water is envisaged to be lowered to about 7.0 by the charge distribution on the metal ion and also helped by Glu-196 by the hydrogen bonding through Thr-199.

An alternative approach to representing the metal center has been developed for zinc(II) centers and applied to the modeling of the interaction of natural substrates and inhibitors of the enzyme human carbonic anhydrase[105 392,3931. Structurally characterized four-, five- and six-coordinate small-molecule complexes of zinc(II) were analyzed to determine the distribution of bond lengths and angles about the zinc ion. A function was developed that was able to reproduce these structural features and was added to the program YETI[394), developed for modeling small molecule-metalloprotein interactions. 

Distribution in Blood. Plasma erythrocyte ratio appears to be concentration-dependent, saturation of the carbonic anhydrase in the erythrocytes occurring at about 40 pg/ml. 

Figure 4.7 Potency difference versus 2D similarity of enz5rme inhibitors. Each data point represents a pair-wise comparison of inhibitors within an activity class. Data points are grayscale-coded according to potency represented as the sum of their pA i values using a continuous spectrum from light grey (lowest combined potency) to black (highest combined potency). Distributions are shown for four sets of enz5me inhibitors that represent different types of SARs, as discussed in the text (a) factor Xa, (h) ribonuclease A, (c) thromboxane S5mthase and d) carbonic anhydrase.

Comoy CW, MarenTH. Fffect of pH on the ocular distribution of a topical carbonic anhydrase inhibitor. Exp Eye Res 1995 6l 213-222. 

Reed M. L. and Graham D. (1981) Carbonic anhydrase in plants distribution and possible physiological roles. In Progress in Phytochemistry (eds. L. Reinhold, J. Harborn, and T. Swain). Pergamon, pp. 47-94. 

Inhibitors to the enzyme carbonic anhydrase. This enzyme is widely distributed in the body and has a fundamental role in the control of acid-base balance. In the 1920s it was noticed that the SULPHONAMIDE sulfanilamide had a weak diuretic action. Acetazolamide is a subsequent thiadiazole-sulphonamide derivative with potent carbonic anhydrase inhibitor activity. Clinically, it is used for antiglaucoma TREATMENT, is a weak diuretic and can be used to treat mountain sickness. Dichlorphenamide and dorzolamide are sulphonamide derivatives also used for antiglaucoma treatment. Methazolamide is used as a diuretic. Now that seven or more isoenzymes of carbonic anhydrase have been cloned. Isolated and mapped, some new initiatives are aimed at developing agents with more selective actions. 

Les.), and Couceiro, de Almeida, and Freire (1953) have localized it histo-chemically in the electrical tissue of Electwphorus electricus L. The distribution of carbonic anhydrase in several tissues of two teleosts and its inhibition in vivo by the sulfonamides have been investigated by Maetz (1953a,b). The presence of cathepsin in the stomachs of various animals including pike and trout has been established by Buchs (1954). A new advance has also been made in the comparative study of pepsin. This enzyme, previously crystallized from salmon (Norris and Elam, 1940), halibut (Eriksen, 1943), and shark (Sprissler, 1942), has now been crystallized from three species of tuna (Norris and Mathies, 1953). These interesting researches have shown that fish pepsins differ in crystal structure, amino acid composition, and specificity from swine or bovine pepsins and show a closer relationship to one another. As pointed out by Velick and Udenfriend (1953), specificity requirements toward substrates are less exacting with extracellular enzymes. 

The measurement of activity, isolation and purification, activation, inhibition, and distribution of carbonic anhydrase have been reviewed (Van Goor, 1948 Vallee and Altschule, 1949 Roughton and Clark, 1951 Weier and Stocking, 1952). A summary of its physical and chemical properties will be given here. 

However, in the study of these compounds, other applications were acquired. The occurrence of carbonic anhydrase, as a functionally important enzyme in the eye and in the central nervous system, led to the use of the inhibitors to treat glaucoma and epilepsy. Methazolamide has certain advantages due to greater penetration and intracellular distribution (17) its principal use is in the treatment of glaucoma. 

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