The Pivotal Role of One-Carbon Metabolism in Neoplastic Progression During the Aging Process DOI Creative Commons
Avisek Majumder,

Shabana Bano,

Kasturi Bala Nayak

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(11), P. 1387 - 1387

Published: Oct. 31, 2024

One-carbon (1C) metabolism is a complex network of metabolic reactions closely related to producing 1C units (as methyl groups) and utilizing them for different anabolic processes, including nucleotide synthesis, methylation, protein reductive metabolism. These pathways support the high proliferative rate cancer cells. While drugs that target (like methotrexate) have been used treatment, they often significant side effects. Therefore, developing new with minimal effects necessary effective treatment. Methionine, glycine, serine are main three precursors vital not only cells but also non-proliferative in regulating energy homeostasis aging process. Understanding potential role crucial advancing our knowledge neoplastic progression. This review provides comprehensive understanding molecular complexities context aging, paving way researchers explore avenues advanced therapeutic interventions cancer.

Language: Английский

Promoting cytidine biosynthesis by modulating pyrimidine metabolism and carbon metabolic regulatory networks in Bacillus subtilis DOI Creative Commons
Xiangjun Zhang, Lu Liu,

Pilian Niu

et al.

Microbial Cell Factories, Journal Year: 2025, Volume and Issue: 24(1)

Published: May 13, 2025

The modification of single or multiple genes via metabolic engineering can lead to the dysregulation central metabolism and affect bacterial growth metabolite accumulation. Meanwhile, transcription factor trigger network reprogramming at global systemic level, redirecting flux toward synthetic pathways target metabolites. In this study, we modulated pyrimidine carbon-nitrogen in Bacillus subtilis through promote synthesis cytidine, a drug intermediate. First, cytidine was enhanced by knocking out transcriptional regulator PyrR, which increased titer during shake flask fermentation 0.67 g/L. Second, mutations catabolite control protein A (CcpA) significantly promoted synthesis, increasing 2.03 Finally, after culture 5 L fermenter, reached 7.65 g/L, 3.77-fold that fermentation. Moreover, yield productivity 0.06 g/g glucose 0.16 g/L/h, respectively, were achieved. Subsequently, regulatory mechanisms PyrR CcpA biosynthesis explored multi-omics analysis. Transcriptome metabolome analysis revealed coordinated alterations carbon, nitrogen, nucleotide, amino acid essential synthesis. However, production recombinant strains attributed enhancement metabolism, Phosphotransferase (PTS) system, tricarboxylic (TCA) cycle, pentose phosphate (PP) pathway, nitrogen metabolism. These results indicate knockdown enhance pathway mutation reprogram network, change flow de novo nucleoside, increase supply precursors accumulation cytidine. Overall, regulation engineered carbon networks is for improving efficiency microbial cell factories.

Language: Английский

Citations

0
Mitochondrial choline import regulates purine nucleotide pools via SLC25A48 DOI Creative Commons
Anthony R.P. Verkerke,

Xu Shi,

Ichitaro Abe

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 1, 2024

ABSTRACT Choline is an essential nutrient for cellular metabolism, including the biosynthesis of phospholipids, neurotransmitters, and one-carbon metabolism. A critical step choline catabolism mitochondrial import synthesis chorine-derived methyl donors, such as betaine. However, underlying mechanisms biological significance remain insufficiently understood. Here, we report that a inner-membrane protein SLC25A48 controls transport in vivo . We demonstrate highly expressed brown adipose tissue required whole-body cold tolerance, thermogenesis, respiration. Mechanistically, uptake into matrix via facilitates betaine Importantly, cells lacking exhibited reduced purine nucleotides failed to initiate G1-to-S phase transition, thereby leading cell death. Taken together, present study identified carrier mediates plays role respiratory capacity, nucleotide synthesis, survival. Key points uptake. Mitochondrial regulates contribution synthesis. Brown fat thermogenesis requires capacity. Cancer require

Language: Английский

Citations

3
Association of Methyl Donor Nutrients’ Dietary Intake and Cognitive Impairment in the Elderly Based on the Intestinal Microbiome DOI Open Access
Qianqian Chen, Rui Fan,

Lixia Song

et al.

Nutrients, Journal Year: 2024, Volume and Issue: 16(13), P. 2061 - 2061

Published: June 28, 2024

Globally, cognitive impairment (CI) is the leading cause of disability and dependency among elderly, presenting a significant public health concern. However, there currently deficiency in pharmacological interventions that can effectively cure or significantly reverse progression impairment. Methyl donor nutrients (MDNs), including folic acid, choline, vitamin B12, have been identified as potential enhancers function. Nevertheless, remains dearth comprehensive research investigating connection between dietary intake MDNs CI. In our study, we comprehensively assessed relationship MDNs’ CI older adults, utilizing 16S rRNA gene sequencing to investigate underlying mechanisms. The results showed an obvious difference methyl-donor nutritional quality index (MNQI) dementia (D) group dementia-free (DF) group. Specifically, was lower MNQI D than DF For gut microbiome, beta diversity flora exhibited higher levels high (HQ) opposed low (LQ) group, comparison Subsequently, performed correlation analysis examine relative abundance microbiota, MDNs, Montreal Cognitive Assessment (MoCA) scores, ultimately identifying ten genera with regulatory functions. Additionally, KEGG pathway analyses suggested one-carbon metabolism, chronic inflammation, DNA synthesis potentially serve pathways through which may be promising for influencing These implied might enhance function regulation microbiota homeostasis. This study offers recommendations prevention management elderly.

Language: Английский

Citations

3
Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism DOI Creative Commons
Baoyi Liu, Ang Li, Yi Liu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: May 31, 2024

SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs the B12-binding protein family responsible for cellular uptake of B12. The role TCN2 in still unclear.

Language: Английский

Citations

2
20-Hydroxyecdysone Boosts Energy Production and Biosynthetic Processes in Non-Transformed Mouse Cells DOI Creative Commons
Oleg Shuvalov,

Yulia Kirdeeva,

Elizaveta Fefilova

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(11), P. 1349 - 1349

Published: Nov. 2, 2024

20-Hydroxyecdysone (20E) is an arthropod steroid hormone that possesses a number of beneficial pharmacological activities in humans, including anabolic, antioxidant, hypoglycemic, cardioprotective, hepatoprotective, neuroprotective, and antineoplastic properties, etc. While several studies have explored the anabolic activity 20E muscle cells, they concentrated on its effects myofibril size, protein biosynthesis intensity, myostatin expression, without assessing energy metabolism. In this research, we demonstrated boosts both catabolism anabolism, coupling energy-producing biosynthetic metabolic processes mouse myoblasts fibroblasts same way. Using transcriptomic approach, identified 20E-mediated up-regulation genes involved different processes. Further experiments revealed increased levels enzymes glycolysis one-carbon It also uptake glucose, glycolysis, respiration, production ATP, global fibroblasts. This phenomenon involves PI3K/AKT/mTOR signaling pathway. Taken together, observed 20E-dependent upregulation metabolism may be main reason for 20E's well-known activity.

Language: Английский

Citations

2
PGD: Shared gene linking polycystic ovary syndrome and endometrial cancer, influencing proliferation and migration through glycometabolism DOI Creative Commons

Jia‐ming Chen,

Weihong Chen, Zhiyi Wang

et al.

Cancer Science, Journal Year: 2024, Volume and Issue: 115(9), P. 2908 - 2922

Published: July 9, 2024

Abstract The relationship among polycystic ovary syndrome (PCOS), endometrial cancer (EC), and glycometabolism remains unclear. We explored shared genes between PCOS EC, using bioinformatics to unveil their pathogenic connection influence on EC prognosis. Gene Expression Omnibus datasets GSE226146 (PCOS) GSE196033 (EC) were used. A protein–protein interaction (PPI) network was constructed identify the central genes. Candidate markers screened dataset GSE54250. Differences in marker expression confirmed mouse human tissues RT‐PCR immunohistochemistry. effect of PGD proliferation migration Ki‐67 Transwell assays. 's impact glycometabolic pathway within carbon metabolism assessed by quantifying glucose content lactic acid production. R software identified 31 common GSE196033. Ontology functional classification revealed enrichment “purine nucleoside triphosphate process,” with key Kyoto Encyclopedia Genes Genomes pathways related “carbon metabolism.” PPI 15 hub HK2 , NDUFS8 PHGDH SMAD3 as candidate markers. analysis validated distinct patterns ovarian tissue tissue, well normal cells. Transfection experiments Ishikawa cells further PGD's cell migration. Suppression impeded cells, suggesting a significant risk factor impacting through modulation single metabolism. These findings highlight pivotal role onset

Language: Английский

Citations

1
Molecular Mechanisms Linking Genes and Vitamins of the Complex B Related to One-Carbon Metabolism in Breast Cancer: An In Silico Functional Database Study DOI Open Access
José María Gálvez-Navas, Esther Molina‐Montes, Miguel Rodríguez‐Barranco

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(15), P. 8175 - 8175

Published: July 26, 2024

Carcinogenesis is closely related to the expression, maintenance, and stability of DNA. These processes are regulated by one-carbon metabolism (1CM), which involves several vitamins complex B (folate, B2, B6, B12), whereas alcohol disrupts cycle due inhibition folate activity. The relationship between nutrients 1CM (all aforementioned alcohol) in breast cancer has been reviewed. interplay genes was also analyzed. Single nucleotide polymorphisms located those were selected considering minor allele frequency Caucasian population linkage disequilibrium. used perform silico functional analyses (considering corrected

Language: Английский

Citations

1
Associations between Circulating Biomarkers of One-Carbon Metabolism and Mitochondrial D-Loop Region Methylation Levels DOI Creative Commons
Andrea Stoccoro,

Martina Lari,

Lucia Migliore

et al.

Epigenomes, Journal Year: 2024, Volume and Issue: 8(4), P. 38 - 38

Published: Oct. 9, 2024

One-carbon metabolism is a critical pathway for epigenetic mechanisms. Circulating biomarkers of one-carbon have been associated with changes in nuclear DNA methylation levels individuals affected by age-related diseases. More and more studies are showing that even mitochondrial (mtDNA) could be methylated. In particular, the displacement (D-loop) region modulates gene expression replication mtDNA and, when altered, can contribute to development human illnesses. However, no study until now has demonstrated an association between circulating D-loop levels.

Language: Английский

Citations

1
Dietary nutrients involved in one-carbon metabolism and colorectal cancer risk DOI Creative Commons
Lin Deng,

Yuchan Huangfu,

Yanhui Ma

et al.

LabMed discovery., Journal Year: 2024, Volume and Issue: unknown, P. 100022 - 100022

Published: Nov. 1, 2024

Language: Английский

Citations

1
Metabolomic Effects of Folic Acid Supplementation in Adults: Evidence from the FACT Trial DOI Creative Commons
Irene Martinez‐Morata,

Haotian Wu,

Marta Gálvez-Fernández

et al.

Journal of Nutrition, Journal Year: 2023, Volume and Issue: 154(2), P. 670 - 679

Published: Dec. 12, 2023

Language: Английский

Citations

3