Coggins P J, McDermott J R, Snell C R, Gibson A M
MRC Neuroendocrinology Unit, Newcastle General Hospital, UK.
Neuropeptides. 1987 Aug-Sep;10(2):147-56. doi: 10.1016/0143-4179(87)90016-3.
The dipeptide, His-Pro, is the major product of the degradation of TRH by rat synaptic membranes in vitro. A small amount of His-Pro is also formed from TRH by the synaptosomal soluble fraction. From inhibitor studies, the main route to His-Pro appears to involve removal of the pGlu residue by membrane-bound metal-dependent pyroglutamylaminopeptidase followed by deamidation. The deamidation step is not mediated by proline endopeptidase (EC3.4.21.26) nor dipeptidylpeptidase-IV (EC3.4.14.5) since it is insensitive to bacitracin and diprotin-A, and may therefore involve a novel membrane-bound TRH metabolizing enzyme. His-Pro is degraded rapidly by the soluble synaptosomal fraction, presumably by prolidase (EC3.4.13.9) and more slowly by the synaptic membrane fraction.
二肽His-Pro是大鼠突触膜在体外降解促甲状腺激素释放激素(TRH)的主要产物。突触体可溶部分也能从TRH生成少量His-Pro。从抑制剂研究来看,生成His-Pro的主要途径似乎是先通过膜结合的金属依赖性焦谷氨酰氨基肽酶去除焦谷氨酸(pGlu)残基,然后进行脱酰胺作用。脱酰胺步骤不是由脯氨酸内肽酶(EC3.4.21.26)或二肽基肽酶-IV(EC3.4.14.5)介导的,因为它对杆菌肽和二肽素-A不敏感,因此可能涉及一种新的膜结合TRH代谢酶。His-Pro被突触体可溶部分迅速降解,推测是由脯氨酰肽酶(EC3.4.13.9)介导,而被突触膜部分降解得较慢。