Carbonic anhydrase

Carbonic anhydrase is an intracellularly localized enzyme (membrane-bound and cytosolic occurrence) that plays a very important role in human metabolism. Carbonic anhydrase catalyzes the reaction CO2 + 2 H2O ⇌ H2CO3 + H2O ⇌ H3O+ + HCO3-. It belongs to the enzyme class 4.2.1.1.

The term carbonic anhydrase does not refer to a single enzyme, but to a whole class of isoenzymes with slightly different protein structures.

In humans, there are 7 different isoenzymes, HCA I to HCA VII (HCA = Human Carbonic Anhydrase), of which HCA II is the best studied.

The enzyme contains a zinc ion as cofactor, which is responsible for the actual catalytic activity of the enzyme. The zinc ion is coordinated to the three nitrogen donor centres of the imidazole ring of the three histidine amino acids.

Carbonic anhydrase is involved in numerous physiological processes. It is one of the fastest enzymes and can hydrate up to 106 molecules of carbon dioxide per second. Its kcat value is 1,000,000 per second.

Carboanhydrase and mode of action in the proximal tubule of the kidney (see Fig.): In the proximal portion of the tubule of the kidneys, the interaction of the Na+-H+ antiporter (see transporter below) and carbonic anhydrase ensures the reabsorption of NaHCO3. In this process, the carbonic anhydrase inhibitors interfere with the renal excretion of HCO3- (mainly in the form of KHCO3) and cause a metabolic acidosis.

Via carbonic anhydrase, hydrogen carbonate is reabsorbed as follows: an Na+ ion enters the cell interior in exchange for an H+ ion, and the proton in the primary urine reacts with HCO3- to form carbonic acid. Under the action of carbonic anhydrase, CO2 is formed and enters the cell directly. Here, an opposite reaction occurs. CO2 is converted back to H2CO3 by the same enzyme, carbonic anhydrase. This intracellular carbonic acid dissociates into an H+ ion, which in turn can be used to exchange for an Na+ ion, and into an HCO3- ion, which is released into the interstitium. It serves as an alkaline reserve for the organism. In addition, the proximal tubule is involved in the resorption of other cations, such as K+, Ca2+ and Mg2+, as well as glucose, amino acids and proteins.

The isoenzyme- and species-specific carbonic anhydrase autoantibodies may inhibit the activity of the enzyme. Some of the antibodies may be directed against the catalytically active epitope of the enzyme. In patients with systemic lupus erythematosus , antibodies against carbonic anhydrase I and II were found in a higher percentage in those patients who had concomitant anti-U1-snRNP and anti-SS-A /Ro.

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