Creatine kinase kinetics, ATP turnover, and cardiac performance in hearts depleted of creatine with the substrate analogue beta-guanidinopropionic acid.
Creatine kinase kinetics, ATP turnover, and cardiac performance in hearts depleted of creatine with the substrate analogue beta-guanidinopropionic acid.
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使用底物类似物 β-胍基丙酸耗尽肌酸的心脏中的肌酸激酶动力学、ATP 周转率和心脏性能。
DOI：
10.1016/0167-4889(85)90148-x
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Seymour,AM
中科院分区：
文献类型：
--
作者：
Shoubridge,EA;Jeffry,FM;Keogh,JM;Radda,GK;Seymour,AM
给大鼠喂食含有 1% 肌酸底物类似物 β-胍基丙酸的饮食，持续 6-10 周。对离体、葡萄糖灌注的工作心脏进行的 31P-NMR 研究表明，胍基丙酸喂养的动物中，[磷酸肌酸]从 22.2 μmol/g 干重降低了 90%，但 [Pi]、[ATP] 或细胞内 pH 值没有变化。肌酸激酶反应中的单向交换通量（磷酸肌酸 → ATP 方向）通过饱和转移 NMR 在 70 cm 水柱灌注压力下工作的心脏中测量。在对照心脏中，这种交换为 10 μmol/g 干重/秒，而在喂饲胍基丙酸的动物心脏中，这种交换降低了 4 倍，达到 2.5–2.8 μmol/g 干重/秒。 Oxygen consumption and cardiac performance were measured in parallel experiments at two perfusion pressures, 70 and 140 cm.在任一工作负荷下，对照大鼠和胍基丙酸喂养大鼠的心脏在摄氧量或任何性能标准方面均未观察到显着差异。 Assuming an ADP:O ratio of 3, the oxygen consumption measurements correspond to ATP turnover rates of 4.2–7.8 μmol/g dry per s. These rates are 1.5–3-times greater than the rate of the phosphocreatine → ATP exchange in hearts from guanidinopropionic acid-fed rats. These data suggest that phosphocreatine cannot be an obligate intermediate of energy transduction in the heart.
Rats were fed a diet containing 1% of the creatine substrate analogue β-guanidinopropionic acid for 6–10 weeks.31P-NMR investigation of isolated, glucose-perfused working hearts showed a 90% reduction in [phosphocreatine] from 22.2 to 2.5 μmol/g dry wt in guanidinopropionic acid-fed animals but no change in [Pi], [ATP], or intracellular pH. The unidirectional exchange flux in the creatine kinase reaction (direction phosphocreatine → ATP) was measured by saturation transfer NMR in hearts working against a perfusion pressure of 70 cm of water. This exchange was 10 μmol/g dry wt per s in control hearts and decreased 4-fold to 2.5–2.8 μmol/g dry wt per s in hearts from guanidinopropionic acid-fed animals. Oxygen consumption and cardiac performance were measured in parallel experiments at two perfusion pressures, 70 and 140 cm. No significant differences were observed in oxygen uptake or in any of the performance criteria between hearts from control and guanidinopropionic acid-fed rats at either workload. Assuming an ADP:O ratio of 3, the oxygen consumption measurements correspond to ATP turnover rates of 4.2–7.8 μmol/g dry per s. These rates are 1.5–3-times greater than the rate of the phosphocreatine → ATP exchange in hearts from guanidinopropionic acid-fed rats. These data suggest that phosphocreatine cannot be an obligate intermediate of energy transduction in the heart.