Recently we noted (Hollak, C. E. M., van Weely, S., van Oers, M. H. J., and Aerts, J. M. F. G.(1994) J. Clin. Invest. 93, 1288-1292) that the clinical manifestation of Gaucher disease is associated with a several hundred-fold increase in chitotriosidase activity in plasma. We report on the purification and characterization of the protein.

Two major isoforms of chitotriosidase with isoelectric points of 7.2 and 8.0 and molecular masses of 50 and 39 kDa, respectively, were purified from the spleen of a Gaucher patient. The N-terminal amino acid sequence of the two forms proved to be identical. An antiserum raised against the purified 39-kDa chitotriosidase precipitated all isozymes. Chitotriosidase activity was earlier found to be completely absent in some individuals. These findings in combination suggest that a single gene may encode the different isoforms of chitotriosidase.

Both the N-terminal sequence and an internal sequence chitotriosidase proved to be homologous to sequences in proteins that are members of the chitinase family (Hakala, B. E., White, C., and Recklies, A. D. (1993) J. Biol. Chem. 268, 25803-25810). The human chitotriosidase described here showed chitinolytic activity toward artificial substrates as well as chitin and may therefore be considered to be a chitinase.

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