Article
Pharmacology & Pharmacy
Zeyad Alehaideb, Ghada Alatar, Atef Nehdi, Abeer Albaz, Hamad Al-Eidi, Mansour Almutairi, Esraa Hawsa, Nora Alshuail, Sabine Matou-Nasri
Summary: This study investigated the effects of C. myrrha resin extracts on the expression of cytochrome P450 (CYP) drug-metabolizing isoenzyme in human hepatocellular carcinoma cell line HepG2. The results showed that both boiled and sonicated C. myrrha extracts modulated the gene expression of CYP 2C8, 2C9, 2C19, and 3A4 at clinically relevant concentrations. However, the extracts were found to be toxic to HepG2 cells at concentrations exceeding 150 mg/ml of the dry crude extract, indicating the need for further research.
SAUDI PHARMACEUTICAL JOURNAL
(2021)
Article
Biochemistry & Molecular Biology
Sonia J. Parikh, Sumit Kamat, Margaret Phillips, Samuel P. Boyson, Thomas Yarbrough, Dylan Davie, Qinghai Zhang, Karen C. Glass, Manish B. Shah
Summary: CYP2C9 enzyme plays a crucial role in metabolizing clinical drugs, and the variant CYP2C9*8 found in individuals of African ancestry affects the clearance of certain drug substrates. The structural and solution characterization of CYP2C9*8 provides valuable insights into the differences in drug binding compared to the wild-type enzyme.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Zelma Faisal, Violetta Mohos, Eszter Fliszar-Nyul, Katerina Valentova, Kristyna Kanova, Beata Lemli, Sandor Kunsagi-Mate, Miklos Poor
Summary: The study investigated the interactions of five silymarin components and their sulfate metabolites with human serum albumin and CYP enzymes. The results showed that each compound tested formed stable complexes with albumin, and certain components/metabolites could inhibit CYP enzymes, with 2,3-dehydrosilychristin-19-O-sulfate exhibiting the strongest inhibitory effect on CYP3A4. Hence, caution should be exercised when administering high doses of silymarin concurrently with medications, as interactions may interfere with drug therapy.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Biochemistry & Molecular Biology
Giovanna Gentile, Ottavia De Luca, Antonio Del Casale, Gerardo Salerno, Maurizio Simmaco, Marina Borro
Summary: Improper drug prescription is a major problem leading to drug-related harms and healthcare resource wastage. Through genomic profiling, we found that only 14.8% of Italian subjects had a fully normal cytochrome profile, while 26.5% had combined cytochrome dysfunction. The discussion focuses on the potential benefits of comprehensive pharmacogenomic testing in polytreated patients to improve drug selection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Yoo-Bin Lee, Vitchan Kim, Sung-Gyu Lee, Gyu-Hyeong Lee, Changmin Kim, Eunseo Jeong, Donghak Kim
Summary: This study demonstrates that allelic variations of human cytochrome P450 2C8 can significantly affect drug metabolism and the production of fatty acid-derived signal molecules. Functional analysis of four newly identified allelic variants showed that V181I, I244V, and L361F variants resulted in a significant reduction in enzyme activity. The L361F variant also exhibited a significant decrease in the efficiency of arachidonic acid epoxidation reactions. These findings suggest that individuals carrying these newly identified P450 2C8 allelic variations may have altered metabolism of clinical medicines and fatty acid-derived signal molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biotechnology & Applied Microbiology
Lihong Jiang, Lei Huang, Jin Cai, Zhinan Xu, Jiazhang Lian
Summary: This article discusses the strategies for improving the expression and activity of eukaryotic P450s in yeast, followed by examples of P450s involved in biosynthetic pathway engineering.
BIOTECHNOLOGY AND BIOENGINEERING
(2021)
Article
Biochemistry & Molecular Biology
Tianxiang Xiao, Kai Lu
Summary: The common cutworm, Spodoptera litura, has developed resistance to commonly used insecticides. Two P450 enzymes, CYP6AE43 and CYP6AE48, play a crucial role in detoxifying pyrethroids and promoting resistance development in S. litura.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Article
Plant Sciences
Hongming Song, Chuankui Wei, Wu Yang, Zhaohe Niu, Mingkai Gong, Haiyan Hu, Haibo Wang
Summary: This study assessed the effect of alpinetin on the activity of cytochrome P450 enzymes (CYP450s) and found that alpinetin inhibited the activity of CYP3A4, 2C9, and 2E1, suggesting potential drug interactions.
PHARMACEUTICAL BIOLOGY
(2022)
Review
Entomology
Ralf Nauen, Chris Bass, Rene Feyereisen, John Vontas
Summary: Insect cytochrome P450 monooxygenases (P450s) play important physiological roles and are particularly involved in the detoxification of xenobiotics. Recent advances in insect genomics and functional approaches have shed light on the evolution of insect P450s, their regulation mechanisms, and the genetic alterations leading to insecticide resistance. Additionally, studies on the sensitivity of beneficial insects to insecticides have provided valuable knowledge for managing P450-mediated resistance and safeguarding their health.
ANNUAL REVIEW OF ENTOMOLOGY
(2022)
Review
Biotechnology & Applied Microbiology
Yifeng Zhang, Lin Ma, Ping Su, Luqi Huang, Wei Gao
Summary: Terpenoids, as the largest family of natural products, play significant roles in medicine, agriculture, cosmetics, and food. Traditional extraction methods have low yields, waste resources, and are not suitable for endangered species. Modern biotech approaches are promising in discovering and characterizing plant terpenoid-related P450 enzymes, and metabolic engineering strategies can be employed to increase terpenoid production.
CRITICAL REVIEWS IN BIOTECHNOLOGY
(2023)
Article
Engineering, Environmental
Toshio Mori, Haruka Ohno, Hirofumi Ichinose, Hirokazu Kawagishi, Hirofumi Hirai
Summary: In this study, it was found that the white-rot fungus P. chrysosporium degrades neonicotinoid insecticides through the activity of at least two different CYP isozymes.
JOURNAL OF HAZARDOUS MATERIALS
(2021)
Article
Chemistry, Multidisciplinary
Peng Jiang, Hongbo Jin, Guangtao Zhang, Wenjun Zhang, Wei Liu, Yiguang Zhu, Changsheng Zhang, Liping Zhang
Summary: This study provides mechanistic understanding of the functional differences between the homologous cytochrome P450 enzymes IkaD and CftA, which catalyze multiple C-H oxidations on the same substrate with distinct regio- and chemoselectivity. The crystal structures reveal that the differences in the conformation of the F/G region in IkaD and CftA control the substrate orientation and determine their binding patterns with polar moieties. Fine-tuning the polar subpocket of IkaD can alter its regioselectivity.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2023)
Article
Agriculture, Multidisciplinary
Jianyi Li, Long Jin, Yuntong Lv, Yaping Ding, Kunpeng Yan, Hang Zhang, Yiou Pan, Qingli Shang
Summary: This study identifies the important roles of cytochrome P450 genes in detoxification of xenobiotics, particularly cyantraniliprole and gossypol, in Spodoptera litura. Several candidate genes were found to confer tolerance to these substances, while knockdown of certain genes increased mortality. Homology modeling and molecular docking analysis indicate the potential of these genes to bind with cyantraniliprole. Overall, this research provides important insights into the detoxification mechanisms and tolerance of S. litura.
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Lisa Marie Schmitz, Felix Hageneier, Katrin Rosenthal, Tobias Busche, David Brandt, Jorn Kalinowski, Stephan Luetz
Summary: Cytochrome P450 monooxygenases play a major role in drug metabolism, and microbial P450s offer advantages in drug synthesis. Actinosynnema mirum strain has been found to have the ability to catalyze reactions on a wide range of substrates, with one substrate, ritonavir, being studied for its metabolic mechanism.
BIOORGANIC & MEDICINAL CHEMISTRY
(2021)
Article
Microbiology
Wadzani Palnam Dauda, Daji Morumda, Peter Abraham, Charles Oluwaseun Adetunji, Shakira Ghazanfar, Elkanah Glen, Shittu Emmanuel Abraham, Grace Wabba Peter, Israel Ogwuche Ogra, Ulasi Joseph Ifeanyi, Hannatu Musa, Mawuli Kwamla Azameti, Bilal Ahamad Paray, Aneela Gulnaz
Summary: This study investigates the diversity, abundance, evolutionary relationships, and cellular localization of 372 cytochrome P450 in 13 Alternaria species. It reveals the expansion of cytochrome P450s in these fungal genera and provides insights into their biology and toxigenic potentials.