Merker M P, Armitage I M, Audi S H, Kakalis L T, Linehan J H, Maehl J R, Roerig D L, Dawson C A
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee 53226, USA.
Am J Physiol. 1996 Feb;270(2 Pt 1):L251-9. doi: 10.1152/ajplung.1996.270.2.L251.
We examined the hydrolysis kinetics of benzoyl-phenylalanyl-glycyl-proline (BPGP) in the isolated perfused lung and in vitro for evidence of preferential hydrolysis of the trans isomer by angiotensin-converting enzyme (ACE). Nuclear magnetic resonance spectroscopy showed that BPGP exists as cis and trans isomers in a ratio of 44:56. After a single pass through the perfused rabbit lung over a wide range of infused BPGP concentrations, 42% of the BPGP was not hydrolyzed. In single-pass bolus-injection studies, 41% of the injected BPGP was not hydrolyzed, and very little further hydrolysis occurred in a second passage of the bolus through the lungs. In rat lung recirculation and in vitro studies of BPGP hydrolysis by ACE, approximately 60% of the substrate was hydrolyzed rapidly compared with the remaining approximately 40%, and the peptidyl-prolyl cis-trans isomerase cyclophilin increased the rate of the slower phase of the reaction in both kinds of experiments. We conclude that the rapid hydrolysis phase represents primarily the hydrolysis rate of the trans isomer and the slower phase the cis-trans isomerization rate, suggesting that the trans isomer of BPGP is preferentially hydrolyzed by ACE in the perfused lung and in vitro.
我们研究了苯甲酰 - 苯丙氨酰 - 甘氨酰 - 脯氨酸（BPGP）在离体灌注肺和体外的水解动力学，以寻找血管紧张素转换酶（ACE）对反式异构体优先水解的证据。核磁共振光谱显示，BPGP以顺式和反式异构体的形式存在，比例为44:56。在多种灌注BPGP浓度下单次通过灌注的兔肺后，42%的BPGP未被水解。在单次推注注射研究中，41%的注射BPGP未被水解，并且推注再次通过肺时几乎没有进一步的水解发生。在大鼠肺循环以及BPGP被ACE体外水解的研究中，与其余约40%相比，约60%的底物被快速水解，并且肽基 - 脯氨酰顺反异构酶亲环蛋白在两种实验中均增加了反应较慢阶段的速率。我们得出结论，快速水解阶段主要代表反式异构体的水解速率，而较慢阶段代表顺反异构化速率，这表明BPGP的反式异构体在灌注肺和体外被ACE优先水解。
