Send to

Choose Destination
Bioorg Med Chem Lett. 2009 Oct 15;19(20):5825-8. doi: 10.1016/j.bmcl.2009.08.088. Epub 2009 Aug 31.

The proteoglycan region of the tumor-associated carbonic anhydrase isoform IX acts as anintrinsic buffer optimizing CO2 hydration at acidic pH values characteristic of solid tumors.

Author information

Universita degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Rm. 188, Via della, Lastruccia 3, I-50019, Sesto Fiorentino (Firenze), Italy.


The enzymatic activities of carbonic anhydrase (CA, EC isozymes CA I, II, IX (catalytic domain (cdCA IX) and catalytic domain plus proteoglycan, flCA IX), XII and XIV were investigated as a function of pH for the CO2 hydration to bicarbonate and a proton. The cytosolic isoforms CA I and II as well as the catalytic domain of CA IX, together with the transmembrane isoforms CA XII and XIV showed sigmoid pH dependencies of k(cat)/KM, with a pKa of 6.90-7.10, showing thus optimal catalytic efficiency around pH 7. The full length CA IX had a similar shape of the pH dependency curve but with a pKa of 6.49, having thus maximal catalytic activity at pH values around 6.5, typical of hypoxic solid tumors in which CA IX is overexpressed. The proteoglycan domain of CA IX (present only in this transmembrane isoform) may thus act as an intrinsic buffer promoting efficient CO2 hydration at acidic pH values found in hypoxic tumors.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center