Carbonic anhydrases carbon dioxide hydration

Carbon atom, 4. See also Atomic orbitals Carbon dioxide hydration, 197-199. See also Carbonic anhydrase Carbonic anhydrase, 197-199,200 Carbonium ion transition state, 154, 159 Carboxypeptidase A, 204-205 Catalysis, general acid, 153,164,169 in carboxypeptidase A, 204-205 free energy surfaces for, 160, 161 in lysozyme, 154... 

Khalifah, R. G. The carbon dioxide hydration activity of carbonic anhydrase. I. Stop-flow kinetic studies on the native human isoenzymes B and C. J. Biol. Chem. 246, 2561-2573(1971). 

Figure 9.23. Effect of pH on Carbonic Anhydrase Activity. Changes in pH alter the rate of carbon dioxide hydration catalyzed by carbonic anhydrase II. The enzyme is maximally active at high pH.

Catalysis of carbon dioxide hydration by carbonic anhydrase is the most rapid enz5fmatic reaction known (Table 9.7). It has been shown (Khalifah, 1971) that the Km for the human forms of the enzyme are between 4 and 9 mM, and the catal5dic turnover number, Vmax/ is 8 X 10 (Table 9.7). 

The Idnetic rate constants for CO2 hydration determined in the laboratory in sterile seawater (Table 4.6) are known sufficiently well that this value should create little uncertainty in the above calculation. However, in natural waters the reaction rates may be enzymatically catalyzed. Carbon dioxide hydration catalysis by carbonic anhydrase (CA) is the most powerful enzyme reaction known (see the discussion in Section 9.3). The catal5dic turnover number (the number of moles of substrate reacted, divided by the number of moles of enz5mie present) is 8 x 10 min for CA (Table 9.7), and marine diatoms are loiown to produce carbonic anhydrase (Morel et al, 1994). The calculations presented in Fig. 10.14 indicate that increasing the CO2 hydration rate constant by 10-fold should increase the gas exchange rate of CO2 in the ocean by 10%-50%. 

Carbon dioxide hydration and HCO dehydration are often coupled to rapid processes, particularly transport processes. Thus, almost all organisms contain enzymes, referred to as carbonic anhydrases, that increase the rate of reaction beyond the already reasonable spontaneous... 

As noted earlier, some carbonic anhydrases can hydrate carbon dioxide at rates as high as a million times a second (10 s ). The magnitude of this can be understood from the following observations. In the first step of a carbon dioxide hydration reaction, the zinc-bound water molecule must lose a proton to regenerate the active form of the enzyme (Figure 9.27). The rate of the reverse reaction, the protonation of the zinc-bound hydroxide ion. is limited by the rate of proton diffusion. Protons diffuse very rapidly with second-order rate constants near 10 M. Thus, the backward rale constant i must be less than 10 s F Because the equilibrium... 

Carbon-dioxide hydration and its mechanism in living systems are of fundamental importance for bioinorganic chemistry. In 1932 the existence of an enzyme catalyzing CO2 hydration in red blood cells was established. The enzyme was named carbonic anhydrase (abbreviated CA). In 1939 the enzyme was recognized to contain zinc. Because CO2 is either the starting point for photosynthesis or the endpoint of substrate oxidation, carbonic anhydrases are now known to be ubiquitous, occurring in animals, plants, and several bacteria. Different... 

Fig. 7 Upper panel currently accepted mechanism for CO2 activation by carbonic anhydrases. Lower panel comparison of reaction profiles for CANH versus three other enzyme active sites, not known to catalyze carbon dioxide hydration (SOR superoxide reductase, Hb hemoglobin, LIPOX...

Essentially, the suggested mechanism includes metabolic production of carbon dioxide, hydration to carbonic acid, catalysis by carbonic anhydrase, dissociation of carbonic acid, and exchange of the hydrogen ions for sodium ions across the luminal border of the cell. 

Carbonic anhydrase is an enzyme that catalyzes the hydration of carbon dioxide to bicarbonate The uncatalyzed hydration of carbon dioxide is too slow to be effective m transporting carbon dioxide from the tissues to the lungs and so animals have devel oped catalysts to speed this process The activity of carbonic anhydrase is remarkable It has been estimated that one molecule of this enzyme can catalyze the hydration of 3 6 X 10 molecules of carbon dioxide per minute... 

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... 

CO3 species was formed and the X-ray structure solved. It is thought that the carbonate species forms on reaction with water, which was problematic in the selected strategy, as water was produced in the formation of the dialkyl carbonates. Other problems included compound solubility and the stability of the monoalkyl carbonate complex. Van Eldik and co-workers also carried out a detailed kinetic study of the hydration of carbon dioxide and the dehydration of bicarbonate both in the presence and absence of the zinc complex of 1,5,9-triazacyclododecane (12[ane]N3). The zinc hydroxo form is shown to catalyze the hydration reaction and only the aquo complex catalyzes the dehydration of bicarbonate. Kinetic data including second order rate constants were discussed in reference to other model systems and the enzyme carbonic anhy-drase.459 The zinc complex of the tetraamine 1,4,7,10-tetraazacyclododecane (cyclen) was also studied as a catalyst for these reactions in aqueous solution and comparison of activity suggests formation of a bidentate bicarbonate intermediate inhibits the catalytic activity. Van Eldik concludes that a unidentate bicarbonate intermediate is most likely to the active species in the enzyme carbonic anhydrase.460... 

Different enzymes exhibit different specific activities and turnover numbers. The specific activity is a measure of enzyme purity and is defined as the number of enzyme units per milligram of protein. During the purification of an enzyme, the specific activity increases, and it reaches its maximum when the enzyme is in the pure state. The turnover number of an enzyme is the maximal number of moles of substrate hydrolyzed per mole of enzyme per unit time [63], For example, carbonic anhydrase, found in red blood cells, is a very active enzyme with a turnover number of 36 X 106/min per enzyme molecule. It catalyzes a very important reaction of reversible hydration of dissolved carbon dioxide in blood to form carbonic acid [57, p. 220],... 

The system illustrated by (272) forms the basis of a model for the zinc-containing metalloenzyme, carbonic anhydrase (Tabushi Kuroda, 1984). It contains Zn(n) bound to imidazole groups at the end of a hydrophobic pocket, as well as basic (amine) groups which are favourably placed to interact with a substrate carbon dioxide molecule. These are both features for the natural enzyme whose function is to catalyze the reversible hydration of carbon dioxide. The synthetic system is able to mimic the action of the enzyme (although side reactions also occur). Nevertheless, the formation of bicarbonate is still many orders of magnitude slower than occurs for the enzyme. 

Carbonic anhydrase an enzyme found in cells and in mucus secretions responsible for the (reversible) hydration of carbon dioxide. 

The two ammonium ions produced from glutamine as illustrated in Figures 8.4 to 8.6 are secreted into the PCT lumen the by a Na+/H+ antiport (the NH4+ substitutes for H+). Subsequent metabolism of 2-oxoglutarate has the potential to generate two bicarbonate ions from the hydration of carbon dioxide by carbonic anhydrase ... 

Human carbonic anhydrase II, found primarily in the erythrocyte, is the prototypical member of the family of carbonic anhydrases and has been extensively reviewed (Pocker and Sarkanen, 1978 Lindskog, 1983, 1986 Silverman and Lindskog, 1988). Within the erythrocyte carbonic anhydrase II hydrates CO2 to form bicarbonate ion plus a proton via tandem chemical processes (Silverman and Lindskog, 1988) (Scheme 2). Most of the carbon dioxide generated during the process of respiration requires this carbonic anhydrase Il-catalyzed event for transport out of the cell. The resultant protons of CO2 hydration are taken up by His-146)8, His-122a, and the amino terminus of the a subunits of the hemoglobin tetramer. As a reference. Scheme 3 outlines the interconversions... 

Carbonic anhydrase influences the tubular reabsorption of sodium in proximal tubule where biocarbonate absorption occurs and in the distal tubule where sodium is exchanged for potassium or hydrogen ion and bicarbonate is formed as the accompanying anion. The hydration of carbon dioxide takes place under the influence of enzyme carbonic anhydrase which forms carbonic acid which dissociates and breaks into hydrogen and carbonate ions. 

This reaction is catalyzed by carbonic anhydrase, an enzyme particularly abundant in erythrocytes. Carbon dioxide is not very soluble in aqueous solution, and bubbles of C02 would form in the tissues and blood if it were not converted to bicarbonate. As you can see from the equation, the hydration of C02 results in an increase in the H+ concentration (a decrease in pH) in the tissues. The binding of oxygen by hemoglobin is profoundly influenced by pH and C02 concentration, so the interconversion of C02 and bicarbonate is of great importance to the regulation of oxygen binding and release in the blood. 

M. Kem, The Hydration of Carbon Dioxide, J. Chem. Ed. 1960,37, 14. Great demonstrations with C02, including one with carbonic anhydrase, are described by J. A. Bell, Every Year Begins a Millennium, J. Chem. Ed. 2000, 77, 1098. 

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