LAPSE:2023.3049v1
Published Article
LAPSE:2023.3049v1
Human Cytochrome P450 2C9 and Its Polymorphic Modifications: Electroanalysis, Catalytic Properties, and Approaches to the Regulation of Enzymatic Activity
February 21, 2023
Abstract
The electrochemical properties of cytochrome P450 2C9 (CYP2C9) and polymorphic modifications P450 2C9*2 (CYP2C9*2) and P450 2C9*3 (CYP2C9*3) were studied. To analyze the comparative electrochemical and electrocatalytic activity, the enzymes were immobilized on electrodes modified with a membrane-like synthetic surfactant (didodecyldimethylammonium bromide (DDAB)). An adequate choice of the type of modified electrode was confirmed by cyclic voltammetry of cytochromes P450 under anaerobic conditions, demonstrating well-defined peaks of reduction and oxidation of the heme iron. The midpoint potential, Emid, of cytochrome P450 2C9 is −0.318 ± 0.01 V, and Emid = −0.324 ± 0.01 V, and Emid = −0.318 ± 0.03 V for allelic variant 2C9*2 and allelic variant 2C9*3, respectively. In the presence of substrate diclofenac under aerobic conditions, cytochrome P450 2C9 and its polymorphic modifications P450 2C9*2 and P450 2C9*3 exhibit catalytic properties. Stimulation of the metabolism of diclofenac by cytochrome P450 2C9 in the presence of antioxidant medications mexidol and taurine was shown.
The electrochemical properties of cytochrome P450 2C9 (CYP2C9) and polymorphic modifications P450 2C9*2 (CYP2C9*2) and P450 2C9*3 (CYP2C9*3) were studied. To analyze the comparative electrochemical and electrocatalytic activity, the enzymes were immobilized on electrodes modified with a membrane-like synthetic surfactant (didodecyldimethylammonium bromide (DDAB)). An adequate choice of the type of modified electrode was confirmed by cyclic voltammetry of cytochromes P450 under anaerobic conditions, demonstrating well-defined peaks of reduction and oxidation of the heme iron. The midpoint potential, Emid, of cytochrome P450 2C9 is −0.318 ± 0.01 V, and Emid = −0.324 ± 0.01 V, and Emid = −0.318 ± 0.03 V for allelic variant 2C9*2 and allelic variant 2C9*3, respectively. In the presence of substrate diclofenac under aerobic conditions, cytochrome P450 2C9 and its polymorphic modifications P450 2C9*2 and P450 2C9*3 exhibit catalytic properties. Stimulation of the metabolism of diclofenac by cytochrome P450 2C9 in the presence of antioxidant medications mexidol and taurine was shown.
Record ID
Keywords
cytochrome P450 2C9, diclofenac, electrochemical analysis, mexidol, polymorphism, taurine
Suggested Citation
Shumyantseva VV, Bulko TV, Koroleva PI, Shikh EV, Makhova AA, Kisel MS, Haidukevich IV, Gilep AA. Human Cytochrome P450 2C9 and Its Polymorphic Modifications: Electroanalysis, Catalytic Properties, and Approaches to the Regulation of Enzymatic Activity. (2023). LAPSE:2023.3049v1
Author Affiliations
Shumyantseva VV: 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
Bulko TV: Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia
Koroleva PI: Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia [ORCID]
Shikh EV: Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, I.M. Sechenov First Moscow Medical State University (Sechenov University), Trubetskaya Str., 8/2, 119991 Moscow, Russia
Makhova AA: Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, I.M. Sechenov First Moscow Medical State University (Sechenov University), Trubetskaya Str., 8/2, 119991 Moscow, Russia
Kisel MS: Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220141 Minsk, Belarus [ORCID]
Haidukevich IV: Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220141 Minsk, Belarus
Gilep AA: Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia; Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220141 Minsk, Belarus
Bulko TV: Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia
Koroleva PI: Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia [ORCID]
Shikh EV: Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, I.M. Sechenov First Moscow Medical State University (Sechenov University), Trubetskaya Str., 8/2, 119991 Moscow, Russia
Makhova AA: Department of Clinical Pharmacology and Propaedeutics of Internal Diseases, I.M. Sechenov First Moscow Medical State University (Sechenov University), Trubetskaya Str., 8/2, 119991 Moscow, Russia
Kisel MS: Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220141 Minsk, Belarus [ORCID]
Haidukevich IV: Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220141 Minsk, Belarus
Gilep AA: Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia; Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus, 220141 Minsk, Belarus
Journal Name
Processes
Volume
10
Issue
2
First Page
383
Year
2022
Publication Date
2022-02-17
ISSN
2227-9717
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PII: pr10020383, Publication Type: Journal Article
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LAPSE:2023.3049v1
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https://doi.org/10.3390/pr10020383
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