Pancreas carbonic anhydrase

Carbonic anhydrase Flavodoxin Hemoglobin Hexokinase Insulin Rubredoxin Superoxide dismutase Bovine erythrocytes Megasphaera elsdenii Bovine blood Yeast Bovine pancreas M. elsdenii Bovine erythrocytes TOMAC/Rewopal HVS/octanol/ isooctane Solubilization [105]... 

Figure 10-5. The environment of the metal in a series of zinc metalloproteins. The proteins are (a) human carbonic anhydrase II, (b) thermolysin from Bacillus thermoproteolyticus, and (c) bovine pancreas carboxypeptidase. Each of these enzymes is, essentially, hydrolytic.

The enzyme carbonic anhydrase facilitates the reaction between carbon dioxide and water to form carbonic acid, which then breaks down to hydrogen (H" ) and bicarbonate (HCOj") ions. This process is fundamental to the production of either acid or alkaline secretions and high concentrations of carbonic anhydrase are present in the gastric mucosa, pancreas, eye and kidney. Because the number of available to exchange with Na" in the proximal tubule is reduced, sodium loss and diuresis occur. But HCOg reabsorption from the tubule is also reduced, and its loss in the urine leads within days to metabolic acidosis, which attenuates the diuretic... 

One of the most important discoveries concerning the biological role of zinc occurred in 1940 when Keilin and Mann showed that zinc is an essential compound of erythrocyte carbonic anhydrase, an enzyme cata-lytically involved in the transport of CO2 in blood (6). Following the 70-year interval between the initial recognition of a metabolic zinc deficiency and the characterization of the first zinc metalloenzyme, there was a period of about 15 years before the second zinc enzyme was identified. In 1955, Vallee and Neurath reported that carboxypeptidase A from bovine pancreas contained 1 g-atom Zn per mol of protein and was essential to the function of the enzyme (7). The presence of zinc in carbonic anhydrase and carboxypeptidase A indicated that a primary role of zinc would be to function in zinc metalloenzymes (62). However, it seemed unhkely that disrupting the activity of carboxypeptidase A or carbonic anhydrase would have profound eflFects on growth. 

The bicarbonate ion (HCO3A is the second-largest anionic contributor to maintaining acid-base balance, and its secretion from the pancreas helps to neutralize the contents of the small intestine. Respiration controlling the carbon dioxide concentration of the blood (PaCOj) and renal excretion of bicarbonate are the two main homeostatic influences on plasma bicarbonate. Within the renal tubular lumen, carbonic anhydrase converts carbonic acid into carbon dioxide, which diffuses into the epithelial cells and forms carbonic acid, which later dissociates to bicarbonate. 

Fig. 1 Active site structures of four zinc-containing enzymes (a) carboxypeptidase A from bovine pancreas, (b) (3-lactamase from Bacteroides fragilis, (c) human carbonic anhydrase. and (d) horse liver alcohol dehydrogenase.

The following three characteristic mammalian liver and kidney enzymes are absent from muscle catalase, xanthine oxidase, and D-amino oxidase. The distribution of many other enzymes in mammals is limited to particular organs. Thus arginase occurs only in the liver, alkaline phosphatase in the intestinal mucosa, acid phosphatase in kidney, spleen, and prostate, 5-nucleotidase in the testis, and a-mannosidase in the epididymis (see Table 4.6). The blood is disproportionately rich in carbonic anhydrase, and the pancreas in ribonuclease. Glutamine synthetase, which condenses... 

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