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The Taste and Smell Clinic

March 2012

Carbonic Anhydrases: Their Roles in Taste and Smell Function


Carbonic anhydrases (CA) are a family of enzymes which initiate and perpetuate taste and smell function. They do this by acting as growth factors which stimulate stem cells in taste buds and olfactory epithelium to develop the complex panoply of structures by which tastants and odorants are perceived.

The presence of CA in taste buds and olfactory epithelium was discovered by histochemical analysis of these enzymes, initially in taste buds, and later in the olfactory epithelium. However, their presence was not initially related to their function in these organs.

We discovered the function of CA VI in taste and smell function by identifying its presence in saliva and nasal mucus. We did this by discovering that patients with loss of taste and smell had diminished quantities of CA VI in saliva and nasal mucus and later we discovered that CA VI was diminished in taste buds of these patients. Serum zinc is a key cofactor in all CA activity. Thus, treating these sensory deficient patients with exogenous zinc increased CA synthesis and restored taste and smell function. In an analogous set of studies making humans and animals zinc deficient inhibited their taste and smell function by inhibiting synthesis of CA VI as shown by decreased CA VI in their saliva and nasal mucus and decreased CA VI in taste buds and olfactory epithelium. Treating humans with drugs which interfered with zinc metabolism (e.g., acetazolamide), used to treat glaucoma, or causing acute zinc depletion (e.g., l-histidine administration) induced taste and smell loss in humans but zinc treatment corrected these losses.

These results only tell part of the story. Other CAs also appear to play a role in taste and/or smell function. CA IV, CA I and CA II have been found in sensory organs, particularly in taste buds. Patients with CA II deficiency, although they commonly exhibit mental retardation, have been reported to exhibit loss of smell. These observations tell us that several CAs play a role in taste and smell function. These CAs, while quite different in their primary protein structure, all have a zinc molecule at their active functional site. If this zinc molecule were inhibited then the function of these enzymes in relationship to their action in promoting taste and smell is inhibited and these sensory functions in humans and animals are lost.

The questions raised by these studies are multiple but one important one is how do these structurally dissimilar enzymes each alter taste and smell function?

I will deal with the answer to this question in April’s What’s New.

References to assist in understanding these processes have been published and reflect a significant series of studies performed in our laboratory and in many other laboratories in the world.

Some of these studies are as follows:

  1. Henkin RI. Growth factors in olfaction. In: Preedy VR, Ed. The Handbook of Growth and Growth Monitoring in Health and Disease. Vol II. New York: Springer-Verlag; 2011, p. 1417-1436.

  2. Henkin RI, Martin BM, Agarwal RP. Efficacy of exogenous zinc in treatment of patients with carbonic anhydrase VI deficiency. Am J Med Sci. 1999;318:392-405.

  3. Thatcher BJ, Doherty AE, Orvisky E, Martin BM, Henkin RI. Gustin from human parotid saliva is carbonic anhydrase VI. Biochem Biophys Res Commun. 1998;250:635-641.

  4. Henkin RI, Patten BM, Re P, Bronzert D. A syndrome of acute zinc loss. Arch Neurol. 1975;32:745-751.

  5. Brown D, Garcia-Segura LM, Orci L. Carbonic anhydrase is associated with taste buds in rat tongue. Brain Res. 1984;324:346-348.

  6. Kimoto M, Iwai S, Maeda T, Yura Y, Fernley RT, Ogawa Y. Carbonic anhydrase VI in the mouse nasal gland. J Histochem Cytochem. 2004;52:1057-1062.

  7. Daikoku H, Morisaki I, Ogawa Y, Maeda T, Kurisu K, Wakisaka S. Immunohistochemical localization of carbonic anhydrase isozyme II in the gustatory epithelium of the adult rat. Chem Senses. 1999;24:255-261.

  8. Leinonen J, Parkkila S, Kaunisto K, Koivunen P, Rajaniemi H. Secretion of carbonic anhydrase isoenzyme VI (CA VI) from human and rat lingual serous von Ebner’s glands. J Histochem Cytochem. 2001;49(5):657-662.