Catabolism of the hemoregulatory peptide N-Acetyl-Ser-Asp-Lys-Pro: a new insight into the physiological role of the angiotensin-I-converting enzyme N-active site.

The tetrapeptide N-Acetyl-Ser-Asp-Lys-Pro (AcSDKP) was first isolated from bone marrow extracts and shown to be involved in the negative control of hematopoiesis by preventing the recruitment of primitive stem cells into S-phase. In vitro studies on AcSDKP catabolism in human plasma revealed that AcSDKP was cleaved by plasmatic angiotensin-I converting enzyme (ACE). The evaluation of the respective involvement of the two active sites of ACE in AcSDKP degradation in vitro revealed that the N-active site was preferentially involved in this catabolism. Moreover, an in vivo study on healthy volunteers of the catalytic efficiency of ACE towards AcSDKP after administration of Captopril demonstrated that AcSDKP was a physiological substrate of ACE. AcSDKP might represent the first natural specific substrate of the N-active site of the enzyme. These results pose the question of a potential role of ACE in the control of hematopoiesis as well as possible applications of ACE inhibitors to cope with dysfunctions in which AcSDKP might exert physiological control.