Cytochrome P450 3A4 electrochemical sensor for testing testosterone metabolism: modulation by luteolin and relevance for food-drug interactions

• Tipo: Artigo em Revista Científica Internacional
• Data: 2025

Autores

Vieira, CSP (Autor) Outra; Cravo, S (Autor) Outra; Emilia Sousa (Autor) FFUP; Marcela A Segundo (Autor) FFUP; Araujo, AN (Autor) FFUP

Revista

Título: Electrochimica Acta

Vol. 540

ISSN: 0013-4686

Editora: Elsevier

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 0 Citações

Outras Informações

ID Authenticus: P-019-XS4

DOI: 10.1016/j.electacta.2025.147201

Abstract (EN): The human body relies on enzymes to carry out biochemical processes. A prime example regarding metabolism of foreign substances is CYP3A4, a major Cytochrome P450 enzyme isoform having testosterone as its natural substrate. This work uses electrochemical biosensing to show, for the first time, how natural compounds modulate testosterone transformation, providing real-time mechanistic insights into enzyme-inhibitor interactions. Commercial carbon screen printed electrodes were modified with a mixture of a synthesized pyrenelinear poly(ethyleneimine) solution, multi-walled carbon nanotubes and CYP3A4 enzyme solution to evidence the catalytic response towards testosterone. The modifications enhanced the electroactive area by 150% compared to the bare electrode, enabled maximal sensitivity of 0.21 A.L.mol-1 in the range from 2.5 to 10 mu M testosterone. The sigmoidal relationship between peak current and testosterone concentration confirmed positive cooperativity in substrate catalysis by CYP3A4, with a Hill number of 2.37+0.18, and apparent Imax of 2.57+0.13 mu A and Km of 7.00+4.00 mu M values. This study also highlights the impact of enzyme activity loss, oxygen levels, and substrate concentration on the experimental results. Importantly, we evaluated luteolin, a dietary flavonoid, for its ability to modulate CYP3A4 activity. The biosensor captured a concentration-dependent decrease in testosterone turnover, suggesting that luteolin can act as an allosteric modulator, altering enzyme-substrate interactions without following classical inhibition kinetics. Altogether, this platform offers a new pathway for rapid assessment of CYP3A4 function and its modulation by small molecules, contributing to drug metabolism studies, nutraceutical screening, and personalized medicine development.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 15