{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:03:42Z","timestamp":1789585422510,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T00:00:00Z","timestamp":1757462400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012190","name":"Ministry of Science and Higher Education of the Russian Federation","doi-asserted-by":"publisher","award":["075-15-2024-643"],"award-info":[{"award-number":["075-15-2024-643"]}],"id":[{"id":"10.13039\/501100012190","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The activity of cytochrome P450 enzymes decreases in older adults, which can lead to toxic effects from polypharmacy. Cytochromes P450 are the most significant enzymes involved in the metabolism of foreign compounds, including pharmaceutical substances. Vitamin B2, or riboflavin (RF), is a potent antioxidant that is vital for the body and participates in numerous enzyme-catalyzed redox reactions. RF is phosphorylated intracellularly to form flavin mononucleotide (FMN), which is further metabolized into flavin adenine dinucleotide (FAD). The active site of the NADPH-dependent cytochrome P450 reductase (CPR), a redox partner of CYP enzymes, is necessary for the catalytic functions of cytochromes P450. The active site of reductase is a complex formed by two types of vitamin B2, such as flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). In our study, we investigated the impact of the phosphorylated form of vitamin B2, FAD, and FMN on the catalytic activity of cytochrome P450 2C9 (CYP2C9) towards non-steroidal anti-inflammatory medications diclofenac and naproxen. It was shown that FAD significantly enhanced the catalytic efficiency of CYP2C9. The 4-hydroxylation of diclofenac was enhanced by 148 \u00b1 10%. The O-demethylation of naproxen showed an increase of 120 \u00b1 14%. Based on these data, we can assume that intake of vitamin B2 (riboflavin) improves catalytic efficiency of CYP2C9. This finding is essential for the modulation of catalytic activity of CYP2C9. The proposed electroanalytic approach is a sensitive and robust method for drug metabolism assay.<\/jats:p>","DOI":"10.3390\/molecules30183673","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T08:43:54Z","timestamp":1757493834000},"page":"3673","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The Activation of Cytochrome P450 2C9 Is Facilitated by the Coenzyme Forms of Vitamin B2"],"prefix":"10.3390","volume":"30","author":[{"given":"Polina I.","family":"Koroleva","sequence":"first","affiliation":[{"name":"Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia"},{"name":"Faculty of Biomedicine, Pirogov Russian National Research Medical University, Ostrovitianov Street, 1, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8772-3214","authenticated-orcid":false,"given":"Alexey V.","family":"Kuzikov","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia"},{"name":"Faculty of Biomedicine, Pirogov Russian National Research Medical University, Ostrovitianov Street, 1, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3621-6482","authenticated-orcid":false,"given":"Andrei A.","family":"Gilep","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia"},{"name":"Institute of Bioorganic Chemistry, 220084 Minsk, Belarus"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0438-9108","authenticated-orcid":false,"given":"Sergey V.","family":"Ivanov","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander I.","family":"Archakov","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia"},{"name":"Faculty of Biomedicine, Pirogov Russian National Research Medical University, Ostrovitianov Street, 1, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1509-7218","authenticated-orcid":false,"given":"Victoria V.","family":"Shumyantseva","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Chemistry, Pogodinskaya Street, 10, Build 8, 119121 Moscow, Russia"},{"name":"Faculty of Biomedicine, Pirogov Russian National Research Medical University, Ostrovitianov Street, 1, 117997 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1921","DOI":"10.1111\/bcp.14094","article-title":"Prescribing medicines to older people\u2014How to consider the impact of ageing on human organ and body functions","volume":"86","author":"Maanen","year":"2020","journal-title":"Br. 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