Møss J, Bundgaard H
Royal Danish School of Pharmacy, Department of Pharmaceutical Chemistry, Copenhagen, Denmark.
Pharm Res. 1990 Jul;7(7):751-5. doi: 10.1023/a:1015875824238.
The kinetics and mechanism of degradation of the tripeptide TRH (pGlu-His-Pro-NH2) and its various primary and secondary degradation products (TRH-OH, His-Pro-NH2, and His-Pro) have been determined in human plasma at 37 degrees C. The rates of degradation of both TRH and TRH-OH (pGlu-His-Pro) showed mixed zero-order and first-order kinetics. At low substrate concentrations first-order kinetics occurred, with TRH and TRH-OH degradation half-lives of 9.4 and 27 min, respectively. The initial step in the plasma-catalyzed degradation of TRH is due to hydrolysis of the pGlu-His bond by the TRH-specific pyroglutamyl aminopeptidase serum enzyme, resulting in the exclusive formation of histidyl-proline amide (His-Pro-NH2). Using specific HPLC methods the major degradation route (67%) of this dipeptide in human plasma was hydrolysis of the peptide bond to yield His and Pro-NH2, whereas deamidation to yield His-Pro accounted for 29% of the total degradation. A minor pathway (less than or equal to 4%) was spontaneous cyclization to yield cyclo(His-Pro). Both His-Pro-NH2 and His-Pro degraded by first-order kinetics and faster than TRH, with half-lives of 5.3 and 2.2 min, respectively, in 80% plasma.
已在37℃的人血浆中测定了三肽TRH（焦谷氨酸-组氨酸-脯氨酸-酰胺）及其各种一级和二级降解产物（TRH-OH、组氨酸-脯氨酸-酰胺和组氨酸-脯氨酸）的降解动力学和机制。TRH和TRH-OH（焦谷氨酸-组氨酸-脯氨酸）的降解速率均呈现零级和一级混合动力学。在低底物浓度下发生一级动力学，TRH和TRH-OH的降解半衰期分别为9.4分钟和27分钟。血浆催化TRH降解的初始步骤是由TRH特异性焦谷氨酸氨肽酶血清酶水解焦谷氨酸-组氨酸键，导致唯一形成组氨酰-脯氨酸酰胺（组氨酸-脯氨酸-酰胺）。使用特定的高效液相色谱方法，该二肽在人血浆中的主要降解途径（67%）是肽键水解产生组氨酸和脯氨酸酰胺，而脱酰胺产生组氨酸-脯氨酸占总降解的29%。一条次要途径（小于或等于4%）是自发环化产生环（组氨酸-脯氨酸）。组氨酸-脯氨酸-酰胺和组氨酸-脯氨酸均通过一级动力学降解，且比TRH降解得更快，在80%血浆中的半衰期分别为5.3分钟和2.2分钟。
