The secretases that cleave angiotensin converting enzyme and the amyloid precursor protein are distinct from tumour necrosis factor‐α convertase

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Abstract
Angiotensin converting enzyme (ACE) and the Alzheimer's amyloid precursor protein are cleaved from the membrane by zinc metalloproteinases termed ACE secretase and α-secretase, respectively. Tumour necrosis factor-α (TNF-α) convertase (ADAM 17) is a recently identified member of the adamalysin family of mammalian zinc metalloproteinases that is involved in the production of TNF-α and possibly in the cleavage of other membrane proteins. Using two different cell-free assays we were unable to detect significant cleavage and secretion of ACE by TNF-α convertase. In addition, there was a different effect of three hydroxamic acid-based inhibitors (batimastat, compound 1 and compound 4) towards TNF-α convertase as compared to ACE secretase and α-secretase. Thus TNF-α convertase would appear to be distinct from, but possibly related to, the secretases that cleave ACE and the amyloid precursor protein.