The processes preceding the detachment of cytochrome c (cyt c) from the inner mitochondrial membrane in intrinsic apoptosis involve peroxidation of cardiolipin (CL) catalyzed by cyt c-CL complex. In the present work, we studied the effect of 17 dietary flavonoids on the peroxidase activity of cyt c bound to liposomes. Specifically, we explored the relationship between peroxidase activity and flavonoids’ (1) potential to modulate cyt c unfolding, (2) effect on the oxidation state of heme iron, (3) membrane permeability, (4) membrane binding energy, and (5) structure. The measurements revealed that flavones, flavonols, and flavanols were the strongest, while isoflavones were the weakest inhibitors of the oxidation. Flavonoids’ peroxidase inhibition activity correlated positively with their potential to suppress Trp-59 fluorescence in cyt c as well as the number of OH groups. Hydrophilic flavonoids, such as catechin, having the lowest membrane permeability and the strongest binding with phosphocholine (PC) based on the quantum chemical calculations exhibited the strongest inhibition of Amplex Red (AR) peroxidation, suggesting a membrane-protective function of flavonoids at the surface. The results of the present research specify basic principles for the design of molecules that will control the catalytic oxidation of lipids in mitochondrial membranes. These principles take into account the number of hydroxyl groups and hydrophilicity of flavonoids.

细胞色素c脱离前的过程(cyt c) 来自线粒体内膜的内在细胞凋亡涉及由 cyt c-CL 复合物催化的心磷脂 (CL) 的过氧化。在目前的工作中，我们研究了 17 种膳食类黄酮对与脂质体结合的细胞色素 c 过氧化物酶活性的影响。具体来说，我们探讨了过氧化物酶活性与类黄酮之间的关系：（1）调节细胞色素 c 解折叠的潜力，（2）对血红素铁氧化态的影响，（3）膜通透性，（4）膜结合能，以及（5） ） 结构体。测量结果表明，黄酮、黄酮醇和黄烷醇是最强的，而异黄酮是最弱的氧化抑制剂。类黄酮的过氧化物酶抑制活性与其抑制细胞色素 c 中 Trp-59 荧光的潜力以及 OH 基团的数量呈正相关。亲水性黄酮类化合物，例如儿茶素，基于量子化学计算，具有最低的膜渗透性和最强的磷酸胆碱 (PC) 结合，表现出最强的 Amplex Red (AR) 过氧化抑制，表明类黄酮在表面具有膜保护功能。本研究的结果详细说明了设计分子的基本原则，这些分子将控制线粒体膜中脂质的催化氧化。这些原则考虑了羟基的数量和类黄酮的亲水性。本研究的结果详细说明了设计分子的基本原则，这些分子将控制线粒体膜中脂质的催化氧化。这些原则考虑了羟基的数量和类黄酮的亲水性。本研究的结果详细说明了设计分子的基本原则，这些分子将控制线粒体膜中脂质的催化氧化。这些原则考虑了羟基的数量和类黄酮的亲水性。