Carbonic anhydrase deficiency

Shringarpure R, Grune T, Davies KJ (2001) Protein oxidation and 20S proteasome-dependent proteolysis in mammalian cells. CeU Mol Life Sci 58 1442-1450 Sly WS, Hu PY (1995) Human carbonic anhydrases and carbonic anhydrase deficiencies. Annu Rev Biochem 64 375 01... 

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... 

Sundaram, V., Rumbolo, P., Grubb, J., Strisciuglio, P, and Sly, W. S., Carbonic anhydrase II deficiency Diagnosis and carrier detection using differential enzyme inhibition and inactivation. Am. J. Hum. Genet. 38,125-136 (1986). 

Sly WS, Hewett-Emmett D, Whyte MP, Yu YS, Tashian RE (1983) Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Proc Natl Acad Sci USA 80 2752-2756... 

Acetazolamide is a carbonic anhydrase inhibitor, used primarily in glaucoma to reduce aqueous humour production. Acetazolamide may cause blood disorders including agranulocytosis (deficiency of neutrophils) as a side-effect. 

From a nutritional viewpoint, Cu2+ competes with zinc ion, as does the very toxic Cd2+. The latter accumulates in the cortex of the kidney. Dietary cadmium in concentrations less than those found in human kidneys shortens the lives of rats and mice. However, some marine diatoms contain a cadmium-dependent carbonic anhydrase.11 Although zinc deficiency was once regarded as unlikely in humans, it is now recognized as occurring mider a variety of circumstances0 p and is well-known in domestic animals.01 Consumption of excessive amounts of protein as well as alcoholism, malabsorption, sickle cell anemia, and chronic kidney disease can all be accompanied by zinc deficiency. 

Acetazolamide can produce severe lactic acidosis, with an increased lactaterpyruvate ratio, ketosis with a low beta-hydroxybutyrateracetoacetate ratio, and a urinary organic acid profile consistent with pyruvate carboxylase deficiency. The acquired enzymatic injury that results from inhibition of mitochondrial carbonic anhydrase V, which provides bicarbonate to pyruvate carboxylase, can damage the tricarboxylic acid cycle. 

Lai, L. W, Chan, D. M, Erickson, R. P, Hsu, S. J. and Lien, Y. H. (1998). Correction of renal tubular acidosis in carbonic anhydrase Il-deficient mice with gene therapy. J. Clin. Invest. 101, 1320-1325. 

Zn Zn2+ 16 mg Over 200 e.g., carbonic anhydrase, carboxypeptidases Sickle cell anemia causes a Zn deficiency... 

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). 

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. 

Reduced activity of carbonic anhydrase, another zinc metalloenzyme, has been reported in gastric and intestinal tissues and in erythrocytes when the activity of the enzyme was expressed per unit of erythrocytes (91), Recently in sickle-cell-disease patients, an example of a conditioned zinc-deficient state, the content of carbonic anhydrase in the red cells was found to be decreased, correlating with the zinc content of the red cells (10,75). Inasmuch as the technique measured the apoenzyme content, it appears that zinc may have a specific eflFect on the synthesis of this protein by some mechanism yet to be understood. 

Numerous metalloenzymes have the ability to remain functional even after the metal, which presumably is present at their active center, has been replaced by another metal (13). Thus in zinc deficiency, if the apoenzyme is synthesized, as has been observed in the case of . coli alkaline phosphatase (13), then other metals which might have accumulated or are normally within the cell could substitute for zinc and generate an active enzyme. Although this is a possibility in the case of microorganisms, it certainly does not appear to be true in the case of experimental animals and man, in that the apoenzymes of alkaline phosphatase, carbonic anhydrase, carboxypeptidase, alcohol dehydrogenase, and de-oxythymidine kinase do not accumulate in zinc-deficient tissues. Thus, one may conclude that a deficiency of zinc does specifically aflFect the activities of zinc-dependent enzymes in sensitive tissues. 

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). 

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