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Revisiting the Metabolism of Donepezil in Rats Using Non-Targeted Metabolomics and Molecular Networking.
Pharmaceutics
January 2025
BK21 FOUR KNU Community-Based Intelligent Novel Drug Discovery Education Unit, College of Pharmacy and Research Institute of Pharmaceutical Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
: Although donepezil, a reversible acetylcholinesterase inhibitor, has been in use since 1996, its metabolic characteristics remain poorly characterized. Therefore, this study aims to investigate the in vivo metabolism of donepezil using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) based on a molecular networking (MN) approach integrated with a non-targeted metabolomics approach. : After the oral administration of donepezil (30 mg/kg) in rats, urine, feces, and liver samples were collected for LC-HRMS analysis.
View Article and Find Full Text PDFA High-Fat Diet Induces Epigenetic 1-Carbon Metabolism, Homocystinuria, and Renal-Dependent HFpEF.
Nutrients
January 2025
Department of Physiology, University of Louisville School of Medicine, Louisville, KY 40202, USA.
Background/objectives: Chronic gut dysbiosis due to a high-fat diet (HFD) instigates cardiac remodeling and heart failure with preserved ejection fraction (HFpEF), in particular, kidney/volume-dependent HFpEF. Studies report that although mitochondrial ATP citrate lyase (ACLY) supports cardiac function, it decreases more in human HFpEF than HFrEF. Interestingly, ACLY synthesizes lipids and creates hyperlipidemia.
View Article and Find Full Text PDFRadical -Adenosylmethionine Sulfurtransferase MybB Catalyzed Formation of the 4-Thiazolidinone Core in Mycobacidin Represents an Intersection between Primary and Secondary Metabolism.
J Am Chem Soc
January 2025
Department of Chemistry, University of Texas at Austin, Austin, Texas 78712, United States.
Mycobacidin is an antitubercular antibiotic structurally composed of a sulfur-containing 4-thiazolidinone ring, yet its biosynthesis including the mechanism of sulfur incorporation has remained an open question since its discovery in 1952. In this study, the mycobacidin biosynthetic gene cluster is identified from soil-dwelling , and the corresponding biosynthetic pathway starting with 7-oxoheptanoate is characterized. The radical SAM enzyme MybB catalyzes two sulfur insertion reactions, thereby bridging C and C to complete the 4-thiazolidinone heterocycle as the final step in mycobacidin maturation.
View Article and Find Full Text PDFHeterologous and High Production of Ergothioneine in by Using Genes from Anaerobic Bacteria.
Metabolites
January 2025
School of Biotechnology, Key Laboratory of Carbohydrate Chemistry, Biotechnology of Ministry of Education, Jiangnan University, Wuxi 214122, China.
Purpose: This study aimed to utilize genetically engineered for the production of ergothioneine (EGT). Given the value of EGT and the application of in enzyme preparation production, we cloned the key enzymes (EanA and EanB) from . Through gene alignment, new ergothioneine synthase genes (EanAN and EanBN) were identified and then expressed in to construct strains.
View Article and Find Full Text PDFImproved protocol for metabolite extraction and identification of respiratory quinones in extremophilic Archaea grown on mineral materials.
Front Microbiol
January 2025
UPR4301 Centre de Biophysique Moléculaire (CBM), Orléans, France.
We investigated the metabolome of the iron- and sulfur-oxidizing, extremely thermoacidophilic archaeon grown on mineral pyrite (FeS). The extraction of organic materials from these microorganisms is a major challenge because of the tight contact and interaction between cells and mineral materials. Therefore, we applied an improved protocol to break the microbial cells and separate their organic constituents from the mineral surface, to extract lipophilic compounds through liquid-liquid extraction, and performed metabolomics analyses using MALDI-TOF MS and UHPLC-UHR-Q/TOF.
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