Rousseau-Plasse A, Lenfant M, Potier P
Centre National de la Recherche Scientifique, Institut de Chimie de Substances Naturelles, Gif sur Yvette, France.
Bioorg Med Chem. 1996 Jul;4(7):1113-9. doi: 10.1016/0968-0896(96)00104-6.
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.
四肽N-乙酰基-丝氨酸-天冬氨酸-赖氨酸-脯氨酸（AcSDKP）最初是从骨髓提取物中分离出来的，并被证明通过阻止原始干细胞进入S期参与造血的负调控。对人血浆中AcSDKP分解代谢的体外研究表明，AcSDKP被血浆中的血管紧张素I转换酶（ACE）裂解。对ACE的两个活性位点在体外AcSDKP降解中各自作用的评估表明，N-活性位点优先参与这种分解代谢。此外，一项对健康志愿者在服用卡托普利后ACE对AcSDKP催化效率的体内研究表明，AcSDKP是ACE的生理底物。AcSDKP可能是该酶N-活性位点的首个天然特异性底物。这些结果提出了ACE在造血调控中的潜在作用问题，以及ACE抑制剂在应对AcSDKP可能发挥生理调控作用的功能障碍方面的可能应用。
