Carbonic acid anhydrase, zinc

Of the more than 300 known zinc enzymes, about 20 have known structures based on X-ray study in the crystalline state and/or nmr data for solutions.126 With structural data it is possible to draw inferences as to the mechanisms. This has been done in some detail for several, of which carbonic acid anhydrase and carboxypeptidase are important examples. 

One of the simplest biochemical addition reactions is the hydration of carbon dioxide to form carbonic acid, which is released from the zinc-containing carbonic anhydrase (left, Fig. 13-1) as HC03-. Aconitase (center, Fig. 13-4) is shown here removing a water molecule from isocitrate, an intermediate compound in the citric acid cycle. The H20 that is removed will become bonded to an iron atom of the Fe4S4 cluster at the active site as indicated by the black H20. An enolate anion derived from acetyl-CoA adds to the carbonyl group of oxaloacetate to form citrate in the active site of citrate synthase (right, Fig. 13-9) to initiate the citric acid cycle. 

Zinc is the second most important of the essential trace elements for humans. It is a constituent of some enzymes, such as carbonic anhydrase. Zinc is sufficiently abundant that deficiencies of zinc are unknown. The highest levels of zinc are found in shellfish, which may contain 400 ppm. The level of zinc in cereal grains is 30 to 40 ppm. When acid foods such as fruit juices are stored in galvanized containers, sufficient zinc may be dissolved to cause zinc poisoning. The zinc in meat is tightly bound to the myofibrils and has been speculated to influence meat s water-binding capacity (Hamm 1972). 

CARBONIC ACID, ZINC SALT (LI) see ZEJ050 CARBONIC ANHYDRASE INHIBITOR NO, 6063 see AAI250... 

Figure 4 A zinc metallo-enzyme carbonic anhydrase for the very fast reversible formation of carbonic acid, H2CO3 from CO2 and H2O. Note the complexity of the protein required apparently to secure selectivity and the constrained, S-coordInate, state of the zinc. There is a channel for substrates to the zinc in contrast to the copper site shown in Figure 3.

Carbonic anhydrases catalyze the reaction of water with carbon dioxide to generate carbonic acid. The catalysis can be extremely fast molecules of some carbonic anhydrases hydrate carbon dioxide at rates as high as 1 million times per second. A tightly bound zinc ion is a crucial component of the active sites of these enzymes. Each zinc ion binds a water molecule and promotes its deprotonation to generate a hydroxide ion at neutral pH. This hydroxide attacks carbon dioxide to form bicarbonate ion, HCO3 ". Because of the physiological roles of carbon dioxide and bicarbonate ions, speed is of the essence for this enzyme. To overcome limitations imposed by the rate of proton transfer from the zinc-bound water molecule, the most active carbonic anhydrases have evolved a proton shuttle to transfer protons to a buffer. 

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). 

Zinc is an essential trace element and is commonly ingested as a nutritional supplement. Divalent zinc is one of the most important of the micronutrients. More than 100 enzymes are zinc dependent for example, carboxypeptidase, carbonic anhydrase (which is responsible for the exchange of carbonic acid in the blood and the exhalation of carbon dioxide), and the alcohol dehydrogenase (which metabolizes alcohol). Deficiency of zinc, especially in newborns, results in impaired growth, loss of hair, skin eruptions, and often impaired or delayed sexual maturation. Many medical problems are also associated with zinc deficiencies (e.g., ulcerative colitis, chronic renal disease, and anemia). 

Cadmium pseudohalides, 981 solid state, 985 Carbamic acid, thio-metal complexes, 978 Carbaplatinaboranes conformation, 374 Carbazide, thio-metal complexes, 978 Carbonic anhydrases zinc, 1001,1004 zinc-carbonyl mechanism, 1003 Carbon monoxide estimation... 

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. 

Many enzymes are conjugated proteins, formed by combination of a simple protein, called the apoenzyme (apo means off, separated from), and one or more other molecules or ions, called coenzymes. Some coenzymes are metal ions. An example is the carbonic anhydrase in human erythrocytes. The apoenzyme has molecular mass 28,000 d. It combines with one zinc ion, Zn" " , to form the active enzyme, which catalyzes the decomposition of carbonic acid to water and carbon dioxide. Another example is the amylase in human saliva, which helps digest starch. It has molecular mass 50,000 d, and requires one calcium ion, Ca" " , as coenzyme. Many enzymes have vitamins or derivatives of vitamins as coenzymes. 

Carbonic anhydrase is a zinc-based enzyme that catalyzes the conversion of carbon dioxide to carbonic acid. In an experiment to study its effect, it was found that the molar concentration of carbon dioxide in solution decreased from 220 mmol dm" to 56.0 mmol dm" in 1.22 x 10 s. What is the rate constant of the first-order reaction ... 

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. 

L-amino acids as effident activators of zinc enzyme carbonic anhydrase. Liebigs Annalen der Chemie,... 

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. 

The Bronsted relationship can be strictly accurate only over a certain range of acid and base strengths. When has diffusion-controlled values, which of course cannot be exceeded, the linear plot of log k/ y vs log must level off to a zero slope, that is a = 0. As well as being reported, although rarely, in simple metal complexes, the resultant curvature in the Bronsted plot is also shown by the zinc enzyme carbonic anhydrase (Chap. 8. Zn(II)). In... 

Zinc is a microelement essential for proper functioning of the human body. The level of daily demand for zinc was established as 13 to 16 mg (Ziemlahski, 2001). Zinc plays a role in protein and carbohydrate metabolism and is a component of over 60 metaloenzymes, including alkaline phosphatase, pancreatic carboxypeptidases A and B, alcoholic and lactic dehydrogenases, carbonate anhydrase, and proteases. It also forms bonds with nucleic acids -which is very important for their functioning (Prasad, 1983 Valee and Falchuk, 1993). 

Figure 7.1 (a) The denatured conformation of the zinc metalloenzyme carbonic anhydrase and the ESI mass spectra obtained under acidic denaturing conditions, (b) The ESI mass spectra obtained under native-state conditions. The decon-voluted ESI mass spectra of carbonic anhydrase reveals the protein molecular weight. The three dimensional structure is protein Data Bank ID IBNl. 

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