Carbonic anhydrase — carbonate

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... 

Part of the metabolic machinery of an osteoclast resembles the red cell and the renal tubule cells because all of these cell types contain the enzyme carbonic anhydrase (carbonate dehydratase) which generates acid, that is protons, and have ion pumps in their plasma membranes. The mechanism of bone resorption requires the action of cathepsin and metalloproteinase-9 working in an acidic environment (Figure 9.8). 

Carbonate anhydrase (carbonic anhydrase, EC 4.2.1.1) catalyzes the reversible interconversion of C02 and HCO3 (see Sect. 3.7.3). The enzyme is found in erythrocytes, and in kidney and gastric juices where it contributes to the control of the acid-base balance. The esterase activity of carbonic anhydrase is probably due to the similarity between its active site and that of the zinc proteases. A possible physiological role of the esterase activity of this enzyme remains to be established. 

Carbonic anhydrase (carbonate dehydratase, EC 4.2.E1) is a small, monomeric zinc-containing metalloenzyme that catalyzes the reversible hydration of C02 to bicarbonate [101][102], In addition to this activity, carbonic anhydrase also catalyzes the hydrolysis of many aromatic esters [103]. 

Carbonate dehydratase, see Carbonic anhydrase Carbonic anhydrase C (Lindskog et al., 1971)... 

Four examples of catalytic or regulatory zinc proteins are reviewed here, and the discussion of metalloprotein function is set within the context of the metal ion and its coordination polyhedron. In the zinc enzymes carbonic anhydrase (carbonate dehydratase) II and carboxypeptidase A, the coordination polyhedron of the metal ion changes as the... 

Proposed role of Zn2+ in carbonic anhydrase. Carbonic anhydrase catalyzes the reaction H20 + C02, HC03 + H+. In the enzyme, Zn2+ forms a complex with H20. Proton displacement generates an OH- ion still bound to the Zn2+. Nucleophilic attack of C02 by the OH- ion generates bicarbonate. 

The Turnover Number of Carbonic Anhydrase Carbonic anhydrase of erythrocytes (Mr 30,000) has one of the highest turnover numbers we know of. It catalyzes the reversible hydration of C02 ... 

This reaction occurs throughout the body and in certain circumstances is speeded up by the enzyme carbonic anhydrase. Carbonic acid is a weak acid and with bicarbonate, its conjugate base, forms the most important buffering system in the body. 

Are they a form of carbonic anhydrase Carbonic anhydrases (CAs) play an important role in photosynthetic carbon fixation, converting HC03 (aq) in seawater to CO2. It is possible that the copper complexes of these peptides perform this function. Evidence from the studies by van den Brenk et al show that patellamide D (4) forms [PatDH + Cu2 + C02]" and [PatDHa + Cui + COa] complexes in the mass spectrometer lending credence to this proposal. 

The molecular components of many buffers are too large to reach the active site of carbonic anhydrase. Carbonic anhydrase II has evolved a proton shuttle to allow buffer components to participate in the reaction from solution. The primary component of this shuttle is histidine 64. This residue transfers protons from the zinc-bound water molecule to the protein surface and then to the buffer (Figure 9.30). Thus, catalytic function has been enhanced through the evolution of an apparatus for controlling proton transfer from and to the active site. Because protons participate in many biochemical reactions, the manipulation of the proton inventory within active sites is crucial to the function of many enzymes and explains the prominence of acid-base catalysis. 

About two-thirds of the zinc in plasma is loosely bound to albumin. Most of the remaining zinc is tightly bound to other plasma proteins. A small fraction (2-3%) of plasma zinc is weakly boimd to amino acids. The amino acids that most avidly bind zinc are histidine and cysteine. Amino acid-associated zinc enters the glomerular filtrate and thus is a source of the zinc ions destined for excretion in the urine. Most of the filtered zinc is reabsorbed and is prevented from immediate excretion. The zinc in red blood cells is bound to carbonic anhydrase. Carbonic anhydrase is present at a level about 0.1% that of hemoglobin in the red blood cell on a per-weight basis. The zinc content of mitochondria is about 1 nmol/mg protein (Link and Jagow, 1995). 

One form of osteopetrosis is caused by a deficiency of one of the isoenzymes of carbonic anhydrase (carbonic anhydrase II). This is an autosomal recessive disorder and... 

Figure 7.20 Carbon dioxide and pH. Carbon dioxide in the tissues diffuses into red blood cells, Inside a red blood cell, carbon dioxide reacts with water to form carbonic acid, in a reaction catalyzed by the enzyme carbonic anhydrase. Carbonic acid dissociates to form HCOj and H , resulting in a drop in pH inside the red cell.

Proximal tubular epithelial cells are richly endowed with the zinc metalloenzyme carbonic anhydrase, which is fonnd in the luminal and basolateral membranes (type IV carbonic anhydrase, an enzyme tethered to the membrane by a glycosylphosphatidylinositol linkage), as well as in the cytoplasm (type 11 carbonic anhydrase). Carbonic anhydrase plays a key role in NaHCOj reabsorption and acid secretion. 

Diagrammatic representation of the production of stomach acid. Carbon dioxide from metabolic processes is converted to carbonic acid under the influence of carbonic anhydrase. Carbonic acid and sodium chloride dissociate, hydrogen ion is actively pumped across the parietal cell membrane and associates with free chloride ion. The remaining sodium and bicarbonate ions combine and remain in the plasma to be utilized in the acid-base buffering system. 

Carbonic anhydrase Carbonic anhydrase acts as a buffer to maintain the pH of blood (see Chapter 5 for details on acid-base chemistry). 

CO2 can be hydrated spontaneously, but in the tubular cell the conversion of CO2 into H2CO3 is catalyzed by an enzyme called carbonic anhydrase. Carbonic anhydrase activities are greater in the cortical portion of the kidney than in the medulla. This is in agreement with micropuncture and stop-flow studies, which suggest that the urine is acidified in the distal part of the nephron, possibly in the collecting ducts. Yet the proximal tubule may also participate in hydrogen secretion. 

The speed of reaction within the erythrocytes is about 13 000 times faster than in the plasma. This accounts both for the rapid uptake of carbon dioxide by the blood during the short transit time (about one sec.) of blood through the systemic capillary and for the rapid release of carbon dioxide from the blood to the alveolar gas during the transit of the blood through the pulmonary capillaries. Without carbonic anhydrase, carbon dioxide partial pressures in the venous blood, and hence in the tissues would be much higher. Indeed when... 

Biochemical Aspects. The zinc-containing metalloenzyme carbonic anhydrase (carbonic hydro-lyase, EC 4.2.1,1) is specifically inhibited by univalent anions and by aromatic sulphonamides. AfT (25 for the binding reactions between bovine carbonic anhydrase and 3-methyl-2-acetylimino-l,3,4-thiadiazoline-5-sulphonamide (Methazolamide) is — 59.0kJmol and that for 5-phenyl-sulphonamido-l,3,4-thiadiazole-2-sulphonamide (CL 11366) is — 57.7kJmol" The thermodynamic quantities did not correlate with the assumed structural features of the binding process. ... 

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