Carbonic anhydrase reaction

Not unexpectedly, the carbonic anhydrase reaction sequence is more complicated. We give it and make comparison with the above sequence in the next section. 

The carbonyl sulfide formed in reaction ii may be converted to monothiocarbonate by carbonic anhydrase (reaction viii). Monothiocarbonate may further spontaneously degrade in reaction ix, regenerating carbonyl sulfide or forming carbon dioxide and sulfide bisulfide ion (HS) (reaction vii). 

As in (i) above, the carbonic anhydrase reaction forms protons (H+) and the new HCO3 " is secreted into the peritubuiar piasma. This time, the protons (H ) associate with monohydrogen phosphate ions (HF04 ) to form dihydrogen phosphate (H2P04") which is excreted in the urine... 

The gastric mucosa attempts to replace the lest H by the carbonic anhydrase reaction but the result Is formation of HCOs" which accumulates In the blood Increasing the pH... 

Carbonic anhydrase is assumed to be located at the surface of the membrane of the tubular cells [47, 48]. Carbonic anhydrase is a small zinc protein found in many animal tissues, but its concentration is highest in the kidney tubules cells, the erythrocyte, and some cells of the gastric mucosa. The substrates of the carbonic anhydrase reaction are carbon dioxide and water the product is carbonic acid. The enzyme has been purified from erythrocytes, and its molecular weight is about 30,000. The purified enzyme preparation contains 0.21% zinc, probably 1 atom of zinc per molecule of enzyme. The zinc is tightly bound to the enzyme molecule and cannot be removed by dialysis or electrodialysis. The presence of zinc in the molecule is essential to activity because when zinc is removed from the molecule by extended incubation with 1-10 phenanthroline, the enzyme s activity reflects the zinc content of the preparation. 

Part of the HC03 reabsorption is the consequence of the direct (not involving carbonic anhydrase) reaction of CO2 with H2O to yield H2CO3. This mechanism depends upon the PCO2, and it explains why the threshold of bicarbonate reabsorption varies... 

Scheme 21.3 Synthesis of a water-soluble cryptophanes for the complexation of human carbonic anhydrase [reaction conditions (a) HCIO4, MeOH, rt, 14 h, 48 % (b) Sulfonamide linker, CUSO4,...

Many important biochemical reactions involve Lewis acid Lewis base chemistry Carbon dioxide is rapidly converted to hydrogen carbonate ion m the presence of the enzyme carbonic anhydrase... 

FIGURE 1.19 Carbonic anhydrase, a representative enzyme, and the reaction that it catalyzes. Dissolved carbon dioxide is slowly hydrated by water to form bicarbonate ion and... 

At 20 C, the rate constant for this uncatalyzed reaction, uncat is 0.03/sec. In the presence of the enzyme carbonic anhydrase, the rate constant for this reaction, is 10 /sec. 

Thus carbonic anhydrase accelerates the rate of this reaction 3.3 X 10 times. Carbonic anhydrase is a 29-kD protein. 

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 ... 

Food containing salicylate (curry powder, paprika, licorice, prunes, raisins, and tea) may increase the risk of adverse reactions. Coadministration of the salicylates with activated charcoal decreases the absorption of the salicylates. Antacids may decrease the effects of the salicylates. Coadministration with the carbonic anhydrase inhibitors increases the risk of salicylism. Aspirin may increase the risk of bleeding during... 

Adverse reactions associated with short-term therapy with carbonic anhydrase inhibitors are rare. Long-term use of these drug s may result in fever, rash, paresthesia... 

Thiazide and related diuretics, loop diuretics, potassium-sparing diuretics, carbonic anhydrase inhibitors, triamterene Avoid exposure to sunlight or ultraviolet light (sunlamps, tanning beds) because exposure may cause exaggerated sunburn (photosensitivity reaction). Wear sunscreen and protective clothing until tolerance is determined. 

The approach taken above estimates the effect of the metal by simply considering its electrostatic effect (subjected, of course, to the correct steric constraint as dictated by the metal van der Waals parameters). To examine the validity of this approach for other systems let s consider the reaction of the enzyme carbonic anhydrase, whose active site is shown in Fig. 8.6. The reaction of this enzyme involves the hydration of C02, which can be described as (Ref. 5)... 

FIGURE 8.8. Calculated free-energy profile for the reaction of carbonic anhydrase. g2(a) and g2(b) designate the states where the proton acceptors are water and histidine respectively. 

Osteopetrosis (marble bone disease), characterized by increased bone density, is due to inability to resorb bone. One form occurs along with renal tubular acidosis and cerebral calcification. It is due to mutations in the gene (located on chromosome 8q22) encoding carbonic anhydrase II (CAII), one of four isozymes of carbonic anhydrase present in human tissues. The reaction catalyzed by carbonic anhydrase is shown below ... 

Carbonic anhydrase (CA) exists in three known soluble forms in humans. All three isozymes (CA I, CA II, and CA III) are monomeric, zinc metalloenzymes with a molecular weight of approximately 29,000. The enzymes catalyze the reaction for the reversible hydration of C02. The CA I deficiency is known to cause renal tubular acidosis and nerve deafness. Deficiency of CA II produces osteopetrosis, renal tubular acidosis, and cerebral calcification. More than 40 CA II-defi-cient patients with a wide variety of ethnic origins have been reported. Both syndromes are autosomal recessive disorders. Enzymatic confirmation can be made by quantitating the CA I and CA II levels in red blood cells. Normally, CA I and CAII each contribute about 50% of the total activity, and the CAI activity is completely abolished by the addition of sodium iodide in the assay system (S22). The cDNA and genomic DNA for human CA I and II have been isolated and sequenced (B34, M33, V9). Structural gene mutations, such as missense mutation, nonsense... 

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