Ectoenzymes: Their Modulation and Similarity to Certain Enzymes of Intracellular Membranes

Abstract

About a decade ago an attempt was made to lay down a definition of ectoenzymes, and to establish criteria by which one might judge whether an enzyme belongs to this category or not (DePierre and Karnovsky 1974a). The statement of definition read “The plasma membrane of cells may contain enzymes whose active sites face the external medium rather than the cytoplasm, and these enzymes are reffered to as ectoenzymes.” The criteria for ectoenzymes given below are slightly altered from the original wording, but they are, in principle, unchanged from those earlier stated (DePierre and Karnovsky 1973, 1974a, b). They may be outlined as follows, and it is realized that not all criteria have been tested for every enzyme considered to be “ecto”:

• 1) Detection of the enzyme should be possible using intact cells.

• 2) The question must be answered in the negative as to whether the enzyme under examination was released from the cells into the external medium.

• 3) The substrate employed should preferably be one that does not enter the cells. However, if criterion 2 above has not been definitively statisfied, one should guard against a circular argument in which an enzymatic activity is revealed with a substrate that is unable to penetrate into the cells, and this fact is then interpreted to indicate an ectoenzyme based solely on the nature of the substrate.

• 4) When the cells are broken, one should be able to account for any increase in enzymatic activity observed.

• 5) The products of the enzyme reaction should be localized to the exterior of the cell.

• 6) One should be able to inhibit the enzyme, selectively, with a nonpenetrating, covalently linking, reagent.