N-acetyltransferase 1 (NAT1) is a xenobiotic metabolizing enzyme that uses acetyl coenzyme A (AcCoA) as a cofactor for -acetylation of many carcinogens including aromatic amines and alkylanilines. NAT1 is characterized by single nucleotide polymorphisms (SNPs) that may modulate affinity towards AcCoA. In the current study, we used Chinese hamster ovary (CHO) cells stably transfected with human (reference allele) or (variant allele) to measure AcCoA kinetic parameters for -acetyltransferase activity measurements towards -aminobenzoic acid (PABA), 4-aminobiphenyl (4-ABP), β-naphthylamine (BNA), benzidine and 3,4-dimethylaniline (3,4-DMA). Our results showed higher -acetylation rates for each substrate catalyzed by compared to . exhibited higher affinity to AcCoA when catalyzing the -acetylation of BNA and benzidine compared to . The results of the current study provide further insights into differences in carcinogen metabolism among individuals possessing the haplotype.
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http://dx.doi.org/10.3389/fphar.2022.931323 | DOI Listing |
Biomolecules
January 2025
Department of Entomology, University of Arizona, Tucson, AZ 85721, USA.
Pantothenate (Pan), or vitamin B5, is essential for the synthesis of co-enzyme A (CoA), acetyl-CoA, and numerous downstream physiological processes. We previously demonstrated that Pan is not only essential for mosquito survival, but also for the development of malaria parasites within the mosquito, suggesting that targeting Pan and CoA biosynthesis may be a novel approach for malaria control. However, little is known about how Pan is acquired and mobilized within the mosquito.
View Article and Find Full Text PDFSheng Wu Gong Cheng Xue Bao
January 2025
College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, Zhejiang, China.
O-acetyl-L-homoserine (OAH) is a promising platform compound for the production of L-methionine and other valuable compounds, while its low yield and low conversion rate limit the industrial application. To solve these problems, we constructed a strain for high OAH production with the previously constructed L-homoserine producer HS33 as the chassis by systematic metabolic engineering. Firstly, PEP accumulation, pyruvate utilization, and OAH synthesis pathway (overexpressing , , and ) were enhanced to obtain an initial strain accumulating 13.
View Article and Find Full Text PDFActa Biochim Biophys Sin (Shanghai)
January 2025
CAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Chinese Academy of Sciences (CAS), Shanghai 200032, China.
U32 is an industrial strain capable of producing therapeutically useful rifamycin SV. In early days of fermentation studies, nitrate was found to increase the yield of rifamycin along with globally, affecting both carbon and nitrogen metabolism in favor of antibiotic biosynthesis; thus, the (NSE) hypothesis was proposed. Although GlnR is likely the master regulator of the pleotropic effect of NSE, the global metabolism affected by NSE has never been systematically examined.
View Article and Find Full Text PDFSci Adv
January 2025
Laboratory of Mitochondrial Biology and Metabolism, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
Although lipid-derived acetyl-coenzyme A (CoA) is a major carbon source for histone acetylation, the contribution of fatty acid β-oxidation (FAO) to this process remains poorly characterized. To investigate this, we generated mitochondrial acetyl-CoA acetyltransferase 1 (ACAT1, distal FAO enzyme) knockout macrophages. C-carbon tracing confirmed reduced FA-derived carbon incorporation into histone H3, and RNA sequencing identified diminished interferon-stimulated gene expression in the absence of ACAT1.
View Article and Find Full Text PDFOsteoarthr Cartil Open
March 2025
Department of Regeneration Sciences and Engineering, Institute for Life and Medical Sciences, Kyoto University, 53 Shogoin-Kawahara-cho, Sakyo-Ku, Kyoto, 606-8507, Japan.
Objective: Osteoarthritis, a degenerative joint disease, requires innovative therapies due to the limited ability of cartilage to regenerate. Since mesenchymal stem cells (MSCs) provide a cell source for chondrogenic cells, we hypothesize that chemicals capable of enhancing the chondrogenic potential of MSCs with transforming growth factor-beta (TGFβ) in vitro may similarly promote chondrogenesis in articular cartilage in vivo.
Design: Chemical compounds that enhance the TGFβ signaling for chondrogenesis were investigated utilizing mesenchymal stem cells derived from human induced pluripotent stem cells.
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