**5.3 Endothelin-converting enzymes**

Endothelin-converting enzymes (ECE-1 and ECE-2) are type II membrane-bound zinc metalloproteases that cleave the low-activity precursor, Big ET-1 between Trp21 and Val22 to produce mature ET-1 [33]. The two enzymes have 59% overall homology [24–26, 34–36] but differ in pH for maximal activity. ECE-1 has a pH optimum of 7.0, whereas ECE-2 has an optimum pH of 5.5 for its activity. ECE-2 is 250 times more sensitive to the metalloprotease inhibitor phosphoramidon. In humans, ECE-1 has four isoforms, ECE1a-d [34, 37], derived from a single gene by differential splicing of mRNA transcripts. These isoforms differ only in the aminoacid sequence of N-terminus and show comparable efficiency in catalyzing the cleavage of Big ET-1 into mature ET-1. ECE-1 is the main enzyme responsible for the transformation of big ETs into ETs [38].
