Article
Chemistry, Analytical
Bassam Lajin, Natascha Schweighofer, Walter Goessler, Barbara Obermayer-Pietsch
Summary: The developed UHPLC-ESIMS/MS method enables the rapid and sensitive determination of caffeine and paraxanthine in biological samples. It offers a 10-fold improvement in detection limit, rapid chromatographic separation, the use of a green chromatographic solvent, direct determination with little sample preparation, and accuracy ensured by isotopically labeled internal standards and qualifier ions. This method is suitable for large clinical studies and provides multiple advantages over current methods.
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)
Article
Environmental Sciences
Teng Wang, Yiqun Han, Haonan Li, Yanwen Wang, Tao Xue, Xi Chen, Wu Chen, Yunfei Fan, Xinghua Qiu, Jicheng Gong, Yifan Xu, Junxia Wang, Weiju Li, Tong Zhu
Summary: Short-term exposure to ambient air particulate matter (PM) is associated with changes in polyunsaturated fatty acids (PUFAs) and oxylipins derived from lipoxygenase (LOX), cytochrome P450 (CYP), and cyclooxygenase (COX) pathways in humans. These findings suggest that bioactive oxylipins could potentially serve as biomarkers and play a crucial role in mediating PM-associated systemic cardiometabolic effects.
ENVIRONMENT INTERNATIONAL
(2021)
Article
Immunology
Ronald Lucarelli, Norma Gorrochotegui-Escalante, Jessica Taddeo, Bettina Buttaro, Joris Beld, Vincent Tam
Summary: Secondary bacterial infection after influenza is a serious clinical complication that may lead to pneumonia and death. Excessive production of CYP450 metabolites during this infection increases vulnerability to secondary bacterial infection. Activation of PPAR alpha inhibits inflammatory signaling and antibacterial activities, while enhancing macrophage polarization to an anti-inflammatory subtype. Partially lacking PPAR alpha in mice during superinfection results in increased lipid metabolism responses and decreased M2-like macrophages.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Biochemical Research Methods
Naifu Zhang, Xiaohe Yu, Xinchao Zhang, Sheena D'Arcy
Summary: Hydrogen-Deuterium eXchange coupled to mass spectrometry is a powerful tool for protein dynamics and interaction analysis. Bottom-up experiments are common for observing deuterium uptake differences, producing multi-dimensional data that can be challenging to visually depict. The HD-eXplosion application fills a gap in available software, generating customizable, publication-quality plots with statistical filters.
Article
Toxicology
Michaela Sadibolova, Risto O. Juvonen, Seppo Auriola, Iva Bousova
Summary: This study investigates the metabolism of helenalin, a sesquiterpene lactone used in European and Chinese folk medicine, revealing differences in metabolic pathways between rats and humans. In humans, hepatic enzymes CYP2B6, CYP3A4, CYP3A5, and CYP3A7, as well as extrahepatic CYP2A13, play significant roles in metabolizing helenalin. The study also shows that helenalin acts as an inhibitor of CYP3A4, CYP3A5, and a mechanism-based inhibitor of CYP2A13.
ARCHIVES OF TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
James F. Markworth, Kristoffer B. Sugg, Dylan C. Sarver, Krishna Rao Maddipati, Susan V. Brooks
Summary: This study found that tendon overuse can lead to a delayed and prolonged local inflammatory response, characterized by an increase in pro-inflammatory eicosanoids and a relative lack of specialized pro-resolving lipid mediators.
Article
Chemistry, Medicinal
Satish R. Malwal, Matthew D. Zimmerman, Nadine Alvarez, Jansy P. Sarathy, Veronique Dartois, Carol A. Nacy, Eric Oldfield
Summary: The study found that SQ109's antibacterial activity against TB is not likely contributed by its metabolites, but rather by the gradual accumulation of non-metabolized SQ109 in tissues to therapeutic levels. This sheds new insights into how SQ109 binds to its target MmpL3.
ACS INFECTIOUS DISEASES
(2021)
Article
Microbiology
Saurav Howlader, Min-Jung Kim, M. Rasheduzzaman Jony, Nguyen Phuoc Long, Yong-Soon Cho, Dong-Hyun Kim, Jae-Gook Shin
Summary: This study characterized the metabolic pathways and enzymes responsible for the metabolism of clofazimine in human liver microsomes. Eight metabolites, including oxidative metabolites, glucuronide conjugates, and sulfate conjugates, were identified. CYP1A2 and CYP3A were involved in the formation of oxidative metabolites, while UGT1A1, 1A3, 1A4, 1A9, and 2B4 were involved in the formation of glucuronide conjugates of oxidative metabolites of clofazimine.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Review
Biochemistry & Molecular Biology
Mariya Misheva, Jethro Johnson, James McCullagh
Summary: Oxylipins play crucial regulatory roles in inflammation, with different classes of oxylipins exerting opposite effects during different stages of inflammation. Understanding the role of oxylipins in inflammatory diseases is essential for elucidating disease onset and prevention.
Article
Chemistry, Multidisciplinary
Jing Liu, Lauritz Harken, Yiling Yang, Xiulan Xie, Shu-Ming Li
Summary: This study reports two important gene clusters involved in the biosynthesis of mycocyclosin and guatyromycine. By reconstructing the biosynthetic pathways and conducting biochemical investigations, it was found that the enzymes encoded by these genes can catalyze both intramolecular oxidation and intermolecular nucleobase transfer reactions, leading to the synthesis of specific natural products.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Chemistry, Analytical
Hugo Jaegler, Alkiviadis Gourgiotis
Summary: The uranium isotope composition in environmental samples can be used to trace its origin. Researchers in the analytical community have been working to improve the detection limit of the U-236/U-238 isotopic ratio using mass spectrometry, specifically the ICP-MS/MS technology. The latest generation of ICP-MS/MS has shown improved performance and can accurately measure U-236/U-238 isotope ratios as low as 10(-11), which is a significant advancement and has various geochemical applications.
JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY
(2023)
Article
Environmental Sciences
Mohd Faheem Khan, Cormac D. Murphy
Summary: This study reports the biotransformation of 6:2 FTOH by Cunninghamella elegans and identifies 5:3 FTCA as the main product. It also confirms the essential role of cytochrome P450 enzymes in this process.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2023)
Article
Multidisciplinary Sciences
Leila Navapour, Navid Mogharrab
Summary: CYP1A2 nsSNPs may affect cancer susceptibility and drug efficiency, with 18 nsSNPs found to be associated with pathogenicity. Further analysis suggests possible association of 9 nsSNPs with the risk of hepatocellular carcinoma.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Sarah M. Glass, Stephany N. Webb, F. Peter Guengerich
Summary: Among the 57 human cytochrome P450 enzymes, seven are mitochondrial and utilize an electron transport system with adrenodoxin (Adx) and NADPHadrenodoxin reductase (AdR) to mediate protein interactions through electrostatic interactions. Experimental and computational studies have shown that despite some differences in interactions, the binding between P450 and Adx is P450-specific.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2021)
