ISSN Print 2500–1094
ISSN Online 2542–1204
BIOMEDICAL JOURNAL OF PIROGOV UNIVERSITY (MOSCOW, RUSSIA)
ORIGINAL RESEARCH
Analysis of mildronate effect on the catalytic activity of cytochrome Р450 3А4
About authors
1 Laboratory of Bioelectrochemistry, Department of Personalized Medicine,
Institute of Biomedical Chemistry, Moscow, Russia
2 Department of Biochemistry, Biomedical Faculty,
Pirogov Russian National Research Medical University, Moscow, Russia
3 Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, Faculty of General Medicine,
I. M. Sechenov First Moscow State Medical University, Moscow, Russia
4 Institute of Bioorganic Chemistry of the National Academy of Sciences, Minsk, Republic of Belarus
Correspondence should be addressed: Victoria Shumyantseva
ul. Pogodinskaya, d. 10, Moscow, Russia, 119121; ur.liam@avestnaymuhs_v
About paper
Funding: this work was conducted under the Federal Fundamental Scientific Research Program for 2013–2020.
Received: 2016-11-28
Accepted: 2016-12-06
Published online: 2017-01-19
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Fig. 1. Electron transfer in a P450-containing monooxygenase system (top) and an electrochemical system (bottom)
Protein structure images — courtesy of PDB database [16], NADPH image — courtesy of PubChem [17].
Fig. 2. Cyclic voltammograms of cytochrome Р450 3A4 (––) and in the presence
of 75 μM mildronate (– –)
The enzyme was immobilized on the electrode modified with DDAB. Scan range: from 0 to –0.6 V (vs. Ag/AgCl); scan rate: 0.05 V/s.
Fig. 3. Dependence of Р450 3A4 reduction current (%) on mildronate concentration (μM), obtained from cyclic voltammetry data. Scan range: from 0 to –0.6 V (vs. Ag/AgCl); scan rate: 0.05 V/s
Fig. 4. Peak currents on square-wave voltammograms under aerobic conditions: (1) P450 3А4; (2) P450 3А4 + diclofenac; (3) P450 3А4 + itraconazole; (4) P450 3А4 + itraconazole + diclofenac; (5) P450 3А4 + erythromycin; (6) P450 3А4 + L-carnitine; (7) P450 3А4 + L-carnitine + diclofenac; (8) P450 3А4 + lipoic (thioctic) acid
Values of current amplitudes were baseline-corrected.
Kinetic parameters of P450 3А4-dependent electrocatalytic N-demethylation of erythromycin
Note. Electrolysis was performed at controlled voltage of –0.5 V (vs. Ag/AgCl) for 20 min in the presence of 100 μM erythromycin.
