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The catalytic mechanism of mammalian carbonic anhydrases

  • Chapter
The Carbonic Anhydrases

Part of the book series: EXS 90 ((EXS,volume 90))

Abstract

The physiological reaction catalyzed by carbonic anhydrase (CA) involves only six atoms at the substrate level: CO2 + H2O ↔ HCO –3 + H+ Despite this simplicity, some aspects of the catalytic mechanism have been elusive, and it is not until recently that a rather detailed picture has emerged of the molecular events taking place in the enzymic active site during a catalytic cycle. These advances are the results of the application of a combination of techniques, such as x-ray crystallography, site-specific mutagenesis, enzyme kinetics and computer simulations. Most of this work concerns the cytosolic high-activity isozyme, human CA II (HCA II), but available evidence indicates that all CAs of the animal type (α-CAs) share the same general mechanism, usually called the zinc-hydroxide mechanism (Silverman and Lindskog, 1988; Silverman, 1991; Lindskog and Liljas, 1993; Liljas et al., 1994; Lindskog 1997). Thus, it is believed that the central catalytic step in all a-CAs is a reaction between CO2 and a zinc-bound OH– ion yielding a coordinated HCO –3 ion, which is displaced from the metal ion by a water molecule. The subsequent regeneration of OH– involves the transfer of H+ from this zinc-bound water molecule to the bulk solution. In this chapter, we will focus on these events as they occur in the active site of HCA II, but specific features of the mechanisms of other mammalian CA isozymes will also be discussed.

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Authors and Affiliations

  1. Department of Biochemistry, Umeå University, S-90187, Umeå, Sweden

    Sven Lindskog

  2. Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL, 32610-0267, USA

    David N. Silverman

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  1. Sven Lindskog
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Editors and Affiliations

  1. Lake Erie College of Osteopathic Medicine, 1858 West Grandview Boulevard, Erie, PA, 16509, USA

    W. Richard Chegwidden

  2. Medical Genetics Unit, St George’s Hospital Medical School, London, SW17 0RE, UK

    Nicholas D. Carter

  3. MRC Human Biochemical Genetics Unit, Wolfson House, University College London, 4, Stephenson Way, London, NW1 2HE, UK

    Yvonne H. Edwards

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Lindskog, S., Silverman, D.N. (2000). The catalytic mechanism of mammalian carbonic anhydrases. In: Chegwidden, W.R., Carter, N.D., Edwards, Y.H. (eds) The Carbonic Anhydrases. EXS 90, vol 90. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8446-4_10

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  • DOI: https://doi.org/10.1007/978-3-0348-8446-4_10

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