Carbonic anhydrase, proton transport

The enzyme carbonic anhydrase promotes the hydration of COg. Many of the protons formed upon ionization of carbonic acid are picked up by Hb as Og dissociates. The bicarbonate ions are transported with the blood back to the lungs. When Hb becomes oxygenated again in the lungs, H is released and reacts with HCO3 to re-form HgCOj, from which COg is liberated. The COg is then exhaled as a gas. 

Tripp BC, Ferry JG. 2000. A structure-function study of a proton transport pathway in a novel gamma-class carbonic anhydrase from Methanosarcina thermophila. Biochemistry 39 9232 0. 

Human carbonic anhydrase II, found primarily in the erythrocyte, is the prototypical member of the family of carbonic anhydrases and has been extensively reviewed (Pocker and Sarkanen, 1978 Lindskog, 1983, 1986 Silverman and Lindskog, 1988). Within the erythrocyte carbonic anhydrase II hydrates CO2 to form bicarbonate ion plus a proton via tandem chemical processes (Silverman and Lindskog, 1988) (Scheme 2). Most of the carbon dioxide generated during the process of respiration requires this carbonic anhydrase Il-catalyzed event for transport out of the cell. The resultant protons of CO2 hydration are taken up by His-146)8, His-122a, and the amino terminus of the a subunits of the hemoglobin tetramer. As a reference. Scheme 3 outlines the interconversions... 

In the red blood cell this reaction plays an important role in COj transport from the tissues to the lungs. In the kidney, the protons of the H3O+ are exchanged for Na+ ions, which are reabsorbed, while HCO3 is decomposed through a shift of the equilibrium to the left. Carbonic anhydrase therefore plays a crucial role in maintaining the ion and water balance between the tissues and urine. 

FIGURE 2.51 A mechanism for sodium chloride uptake, as explained in four steps of increasing complexity (a) The sodium/proton exchanger, (b) The sodium/proton exchanger with catalysis of add production by carbonic anhydrase. (c) The sodium/proton exchanger with catalysis of acid production and utilization of bicarbonate by the bicarbonale/chioride exchanger, (d) The finished model for transport of sodium and chloride ions. 

Proton transport in carbonic anhydrase as an example of the difference between microscopic and phenomenological LFERs 212... 

Braun-Sand, S., Strajbl, M. and Warshel, A. (2004). Studies of proton translocations in biological systems simulating proton transport in carbonic anhydrase by EVB based models. Biophys. J. 87, 2221-2239... 

A small isotope effect for proton transport through a water chain is also observed for catalytic conversion of CO2 to HCO by carbonic anhydrase II [68, 69]. The rate-determining step in this process is the transfer of a proton from the H2O ligand of a four-coordinated zinc ion to a histidine residue located at a distance of about 8 A. The proton conduit is known to consists of water molecules located in a pocket that can contain several such molecules, which are freely exchanged with... 

The gastric mucosa is able to generate a proton gradient of 10 1. The energy required for this transport can in principle be delivered by an ATPase and a search for such an enzyme was indicated. The earlier suggestion that a membrane-bound anion-sensitive ATPase in cooperation with carbonic anhydrase would be responsible, has been considered in Section 2 and found to be unlikely. 

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