Impact of angiotensin-converting enzyme substrate conformation on fractional hydrolysis in lung.
Impact of angiotensin-converting enzyme substrate conformation on fractional hydrolysis in lung.
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血管紧张素转换酶底物构象对肺中部分水解的影响。
DOI：
10.1152/ajplung.1996.270.2.l251
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Dawson,CA
中科院分区：
文献类型：
--
作者：
Merker,MP;Armitage,IM;Audi,SH;Kakalis,LT;Linehan,JH;Maehl,JR;Roerig,DL;Dawson,CA
为了证明血管紧张素转换酶(ACE)对反式异构体的优先水解性，我们研究了苯甲酰苯丙氨酰-甘氨酰-脯氨酸(BPGP)在离体肺和体外的水解动力学。核磁共振波谱表明，BPGP以顺式和反式异构体的形式存在，其比例为44：56。在大范围的BPGP灌流浓度范围内单次通过兔肺灌流后，42%的BPGP没有被水解性。在单次团注研究中，注射的BPGP中有41%没有被水解，在第二次通过肺部的团注中几乎没有发生进一步的水解。在大鼠肺再循环和血管紧张素转换酶体外水解BPGP的实验中，约60%的底物被快速水解，而其余约40%的底物被迅速水解，并且在这两种实验中，肽基-Pro-顺式-反式异构酶亲环素增加了反应的慢速。结果表明，BPGP的快速水解相主要代表反式异构体的水解率，慢速相主要代表顺式-反式异构化速率，提示BPGP的反式异构体在肺灌流和体外实验中优先被ACE水解。
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.