亚离子/酸如何通过生物膜:一项实验和计算研究
Simona Lojevec Hartl1,2, Simon Žakelj2, Marija Sollner Dolenc2
1National Institute of Chemistry, Center for Validation Technologies and Analytics, Ljubljana, Slovenia.
The protein journal
|June 8, 2023
概括
酸 (AHA) 很容易透到生物膜中,但其运输并不是抑制细胞染色体c氧化酶IV的速度限制步骤. 循环传输,而不是膜透性,决定了阿齐德中毒的速度.
科学领域:
- 生物化学 生物化学
- 毒理学 毒理学 毒理学
- 膜生物物理学 膜生物物理学
背景情况:
- 酸 (HN3) 和酸离子 (N3-) (AHA) 是有毒的,在细胞呼吸中抑制细胞染色体c氧化酶复合物IV (CoX IV).
- 在中枢神经和心血管系统中,AHA的毒性尤为重要.
- 由于AHA的电离性,其膜透性取决于pH值.
研究的目的:
- 为了研究亚类物种 (AHA) 穿过生物膜的透性.
- 为了确定AHA的毒性机制中的速度限制步骤,特别是CoX IV抑制.
- 为了将膜传输速率与化学抑制速率相关联.
主要方法:
- 在pH值2.0和8.0下测量了AHA的八醇/水分区系数.
- 利用并行人工膜透性测试 (PAMPA) 来确定生理pH的有效透性.
- 经过验证的实验透率数据与使用Smoluchowski方程的理论估计.
主要成果:
- 八醇/水分区系数为2.01 (pH2.0) 和0.00034 (pH8.0). 这两种分区系数均为2.01 (pH2.0).
- 有效透率 (logPe) 的值为 -4.97 (pH 7.4) 和 -5.26 (pH 8.0).
- 通过细胞膜的透率 (8.46·10^4 s^-1) 显著超过了CoX IV抑制率 (200 s^-1).
结论:
- AHA的膜传输是快速的,而不是CoX IV抑制的速度限制步骤.
- CoX IV 抑制的速度不受 AHA 通过生物膜的传递控制.
- 亚中毒的动态主要由循环运输控制,发生在几分钟内.
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