Endothelin-1 (ET-1)-converting enzyme (ECE) activity in the human serum lipoprotein fraction was studied using a sensitive enzyme immunoassay and reverse-phase high performance liquid chromatography. The ECE activity of cleaving synthetic human big ET-1 into ET-1 by the serum lipoprotein fraction was about 14-times greater than that by whole serum, and the activity was closely associated with lipoprotein itself. The lipoprotein ECE activity, which was optimal at pH 7.0, was inhibited by EDTA, o-phenanthroline, phosphoramidon, thiorphan, phenylmethane-sulfonyl fluoride and chymostatin, but not by cysteine or aspartic proteinase inhibitors, suggesting metalloproteinase- and chymotrypsin-like properties. These results suggest that the serum lipoprotein ECE may be involved in the processing of big ET-1 to ET-1 in the circulatory system.
