Carbonic anhydrases as disease markers

Abstract

Introduction: The physiologic importance of fast CO₂/HCO₃^- interconversion in various tissues requires the presence of carbonic anhydrase (CA, EC 4.2.1.1). Fourteen CA isozymes are present in humans, all of them being used as biomarkers.

Areas covered: A great number of patents and articles were focused on the use of CA isozymes as biomarkers for various diseases and syndromes in the recent years, in an ascending trend over the last decade. The review highlights the most important studies related with each isozyme and covers the most recent patent literature.

Expert opinion: The CAs biomarker research area expanded significantly in recent years, shifting from the predominant use of CA IX and CA XII in cancer diagnostic, staging, and prognosis towards a wider use of CA isozymes as disease biomarkers. CA isozymes are currently used either alone, in tandem with other CA isozymes and/or in combination with other proteins for the detection, staging, and prognosis of a huge repertoire of human dysfunctions and diseases, ranging from mild transformation of the normal tissues to extreme shifts in tissue organization and function. The techniques used for their detection/quantitation and the state-of-the-art in each clinical application are presented through relevant clinical examples and corresponding statistical data.

Keywords: Carbonic anhydrases; biomarker; pathology; physiology.

Figure 1.

Cartoon depicting the 14 human CA isozymes, their relative catalytic activity and subcellular localization. For a more detailed overview, see Table 1.

Figure 2.

CA inhibitors in clinical use, administered either systemically (compounds 1-5, 8, 9) or topically (antiglaucoma compounds 6 and 7, administered directly into the eye). One may notice that all compounds contain a primary sulfonamide/sulfamate group that binds the Zn (II) ion in the active site of CAs.