Tetrahydrofolic acid and formaldehyde are key human metabolites but their physiologically relevant chemistry is undefined. Our NMR studies confirm formaldehyde as a product of tetrahydrofolic acid degradation but also reveal their reaction regulates the stability of tetrahydrofolic acid. These observations identify a novel non-enzymatic feedback mechanism regulating formaldehyde and folate metabolism that has important implications for folate-targeting chemotherapy in cancer and other diseases.
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http://dx.doi.org/10.1039/d1cc01425k | DOI Listing |
Int J Biol Macromol
December 2024
Key Laboratory of Industrial Fermentation Microbiology, Ministry of Education, Tianjin 300457, PR China; Tianjin Key Laboratory of Industrial Microbiology, Tianjin 300457, PR China; College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, PR China. Electronic address:
Soluble cytotoxic oligomers produced during the fibrillation of both α-synuclein (αS) and amyloid-β protein (Aβ) are key pathogenic factors in Parkinson's disease (PD) and Alzheimer's disease (AD). Reducing toxic oligomers by regulating the aggregation process of αS and Aβ is an important strategy for the treatment of PD and AD. Herein, tetrahydrofolic acid (THF) is found to accelerate amyloid fibrillization, decreases cytotoxic oligomers and suppresses their toxicity.
View Article and Find Full Text PDFMol Biol Rep
November 2024
Second School of Clinical Medicine, Henan University of Chinese Medicine, Zhengzhou, 450002, China.
Background: The currently used methods for the detection of methylene tetrahydrofolic acid reductase (MTHFR) C677T single nucleotide polymorphism (SNP) are either time-consuming or expensive. In this study, we devised an accurate, rapid and easy-to-use SNP detection system based on fluorescent primers amplification refractory mutation system qPCR, known as FP ARMS-qPCR.
Methods: Fluorescent primers (FPs) modified by fluorescent dye or quencher near the 3' terminal thymine were designed.
ACS Omega
October 2024
Department of Chemistry, College of Science, Bahir Dar University, Bahir Dar 6000, Ethiopia.
Synthetic antibiotics known as sulfonamides suppress the synthesis of tetrahydrofolic acid, which cures respiratory tract infections and protozoal infections by preventing the creation of dihydrofolic acid. Electrochemical sensors based on tetrakis(1,10-phenanthroline)-μ-(4,4'-bipyridine) dicopper(II) chloride monohydrate ([PCu-Bip-CuP]Cl·HO or simply CuPBCl) have been successfully applied for the determination of sulfamethoxazole (SMX) and trimethoprim (TMP) from samples. The experimental conditions and parameters were optimized to achieve the best electrode performances for simultaneous quantification of SMX and TMP.
View Article and Find Full Text PDFBMC Microbiol
September 2024
Department of Health Science and Technology, ETH Zurich, Institute of Food, Nutrition and Health, Laboratory of Food Biotechnology, Schmelzbergstrasse 7, Zurich, 8092, Switzerland.
Background: Folate (vitamin B9) occurs naturally mainly as tetrahydrofolate (THF), methyl-tetrahydrofolate (M-THF), and formyl-tetrahydrofolate (F-THF), and as dietary synthetic form (folic acid). While folate auxotrophy and prototrophy are known for several gut microbes, the specific folate forms produced by gut prototrophs and their impact on gut auxotrophs and microbiota remain unexplored.
Methods: Here, we quantified by UHPLC-FL/UV folate produced by six predicted gut prototrophs (Marvinbryantia formatexigens DSM 14469, Blautia hydrogenotrophica 10507 , Blautia producta DSM 14466, Bacteroides caccae DSM 19024, Bacteroides ovatus DSM 1896, and Bacteroides thetaiotaomicron DSM 2079 ) and investigated the impact of different folate forms and doses (50 and 200 µg/l) on the growth and metabolism of the gut auxotroph Roseburia intestinalis in pure cultures and during fecal anaerobic batch fermentations (48 h, 37 °C) of five healthy adults.
Int J Biol Macromol
October 2024
College of Chemistry & Pharmacy, Northwest A&F University, Yangling 712100, Shaanxi, China. Electronic address:
DNA damage-based therapy is widely used in cancer treatment, yet its therapeutic efficacy is constrained by the redox homeostasis and DNA damage repair mechanisms of tumor cells. To address these limitations and enhance the efficacy of DNA damage-based therapy, HA-CuH@MTX, a copper-histidine metal-organic complex (CuH) loaded with methotrexate (MTX) and modified with hyaluronic acid (HA), was developed to amplify the DNA damage induced. In vitro experiments demonstrated that the presence of both Cu and Cu in HA-CuH@MTX enables two-way regulated redox dyshomeostasis (RDH), achieved through Cu-catalyzed generation of •OH and Cu-mediated consumption of glutathione, thereby facilitating efficient DNA oxidative damage.
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