磷脂酰胆碱水溶性药物形式对细胞色素P450 2C9和2D6催化活性的作用评估
Role Assessment of Water-Soluble Pharmaceutical Form of Phosphatidylcholine on the Catalytic Activity of Cytochrome P450 2C9 and 2D6.
作者信息
Koroleva Polina I, Bulko Tatiana V, Kuzikov Alexey V, Gilep Andrei A, Romashova Yulia A, Tichonova Elena G, Kostrukova Lyubov V, Archakov Alexander I, Shumyantseva Victoria V
机构信息
Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia.
Faculty of Biomedicine, Pirogov Russian National Research Medical University, Ostrovitianov Street, 1, 117997 Moscow, Russia.
出版信息
Int J Mol Sci. 2024 Dec 24;26(1):4. doi: 10.3390/ijms26010004.
This study aimed to investigate whether the water-soluble pharmaceutical form of phosphatidylcholine nanoparticles (wPC) stimulated the catalytic activity of CYP enzymes 2C9 and 2D6. We have shown that electroenzymatic CYP2C9 catalysis to nonsteroidal anti-inflammatory drug naproxen as a substrate was enhanced from 100% to 155% in the presence of wPC in media. Electroenzymatic CYP2D6 activity in the presence of the adrenoceptor-blocking agent bisoprolol as a substrate was elevated significantly from 100% to 144% when wPC was added to potassium phosphate buffer solution. These results indicate the ability of wPC in the form of the phospholipid ultra-small nanoparticles to work as a membrane additive and crowding agent to accelerate the electroenzymatic reactions of cytochrome P450.
本研究旨在调查磷脂酰胆碱纳米颗粒的水溶性药物形式（wPC）是否能刺激细胞色素P450酶（CYP）2C9和2D6的催化活性。我们已经表明，在培养基中存在wPC的情况下，以非甾体抗炎药萘普生为底物的电酶CYP2C9催化作用从100%提高到了155%。当将wPC添加到磷酸钾缓冲溶液中时，以肾上腺素能受体阻滞剂比索洛尔为底物时的电酶CYP2D6活性从100%显著提高到了144%。这些结果表明，磷脂超小纳米颗粒形式的wPC能够作为膜添加剂和拥挤剂来加速细胞色素P450的电酶反应。
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