Biomedical Chemistry: Research and Methods 2024, 7(1), e00210

Comparative Analysis of Bioelectrocatalytic Cytochrome P450 3A4 Systems

P.I. Koroleva, V.V. Shumyantseva*

Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Moscow 119121, Russia; *e-mail: viktoria.shumyantseva@ibmc.msk.ru

Keywords:electroanalysis, drugs, cytochrome P450 3A4, bioreactor, enzymatic catalysis, electroenzymatic systems, flavin nucleotides, bactosomes

DOI:10.18097/BMCRM00210

The whole version of this paper is available in Russian.

This article describes the approaches developed by the authors with the aim to increase the efficiency of electro enzymatic reactions catalyzed by cytochrome P450 3A4. A comparative analysis of cytochrome P450 3A4 systems was carried out during the formation of functional complexes hemoprotein - flavin nucleotides as low-molecular models of NAD(P)H-dependent cytochrome P450 reductase. The formation of a productive enzyme-substrate complex before the stage of receiving electrons from the modified electrode was studied from electocatalytic viewpoint. Incorporation of the enzyme into nanopores of different nature on the electrode (2D-3D transition) was also studied. The results on the electrochemical reduction of bactosomes as functionally active models of the microsomal monooxygenase system are also considered. The electrochemical and electrocatalytic parameters of cytochrome P450

Figure 1. Prospects for application of cytochrome P450 as biosensors and bioreactors.
Figure 2. Enzyme-substrate complex formation as the first stage of CYP catalytic cycle and the subsequent addition of an electron.
Figure 3. Cyclic voltammograms of CYP3A4 immobilized on SPE modified with DDAB, under aerobic conditions and in the presence of the substrate erythromycin in the potential range from 0.1 to - 0.6 V (vs Ag/AgCl) at a scan rate of 0.1 V/s.
Figure 4. Electron transfer pathway in the CYP system.
Figure 5. Immobilization of CYP3A4 according to the strategy of transition from 2D to 3D surface.

CLOSE
Table 1. Comparison of electroanalytical and electrocatalytical characteristics of the proposed modifications of the electrode surface in order to increase the efficiency of electrocatalysis.

FUNDING

The work was performed within the framework of the Program for Basic Research in the Russian Federation for a long-term period (2021-2030) (№122030100168-2).

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