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At least 19 recordsLinked to original sources
PubMed1975

Redox metabolism of glutathione in the red blood cell.

A theoretical study of the biochemical and clinical aspects of the reduction-oxidation metabolism of glutathione in the mature red blood cell is presented. A summarizing survey of the literature data has led to the formulation of a mathematical model which comprises the kinetic properties of the enzymes partaking in the hexose monophosphate pathway (HMP) and the oxidation of NADPH and GSH. The model takes the form of a system of differential equations describing the motion of metabolites in one cell. The interactions between metabolites ane enzymes, in particular between glutathione and the SH-dependent enzymes of glucose phosphorylation and HMP have been included into the model...

Disulfides↗
PubMed2026

Crosstalk between cysteine and lysine modifications: Integrating redox and metabolic regulation.

Protein post-translational modifications (PTMs) on amino acid residues enable dynamic cellular responses to changes in metabolic and redox state. Cysteine and lysine are among the most extensively modified amino acid residues, with both undergoing a diversity of acylation and oxidative modifications. Indeed, proximal (<10&#x202f;&#xc5;) cysteine and lysine residues may form integration nodes for crosstalk between metabolism and redox homeostasis pathways. This review highlights the interaction of proximal Cys-Lys residues, including influence on residue pKa by local electrostatics, cysteine-to-lysine transfer of PTM moieties, and covalent crosslinking. We discuss candidate Cys-Lys regulatory pairs in proteins involved in redox regulation, proteostasis, metabolic adaptation and inflammation. We further utilize computational modeling to identify proximity between cysteine and lysine residues in proteins known to be regulated by acylation and oxidative PTMs, and to demonstrate changes in these distances and local electrostatic potential due to lysine acetylation. Finally, we review how mass spectrometry-based proteomics and machine-learning PTM predictive tools can enable the identification, validation, and interpretation of proximal Cys-Lys interactions that regulate cellular responses to oxidative challenge and metabolic flux.

Cysteine↗
PubMed2026

Integrated salivary proteomic and metabolomic analyses reveal molecular characterization and novel biomarker panels of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by chronic inflammation, oxidative stress, and metabolic dysregulation. The lack of convenient and easily-accessible non-invasive diagnostic approaches remains a major clinical challenge. This study applied an integrated saliva-based proteomic and untargeted metabolomic strategy to identify potential biomarkers for COPD classification. Comprehensive multi-omics analyses identified 225 differentially abundant proteins and 60 differentially abundant metabolites between patients with COPD and healthy controls, including 24 biologically relevant endogenous metabolites. Functional enrichment analyses revealed pronounced dysregulation of mitochondrial energy metabolism, redox homeostasis, lipid remodeling, and inflammatory-related pathways in COPD. By integrating salivary proteomic and metabolomic biomarkers, a stepwise feature selection combined with LASSO logistic regression was used to construct diagnostic models, yielding an optimized biomarker panel consisting of 11 proteins and 2 endogenous metabolites. This integrated model achieved excellent diagnostic performance, with an area under the ROC curve of 0.96. Collectively, these findings demonstrate that integrated salivary proteomic and metabolomic profiling provides a robust, non-invasive approach for COPD classification and offers a promising foundation for the development of biosensor-based diagnostic platforms and early disease detection. SIGNIFICANCE: Chronic obstructive pulmonary disease (COPD) remains a major global health burden. Current diagnostic approaches rely largely on spirometry and clinical assessment, which are limited in sensitivity for early-stage disease and unsuitable for large-scale screening. This study employs an integrated saliva-based proteomic and metabolomic strategy to identify non-invasive biomarkers for COPD classification. Our findings reveal coordinated dysregulation of mitochondrial energy metabolism, redox homeostasis, and lipid remodeling in COPD, highlighting the interconnected roles of metabolic reprogramming, oxidative stress, and inflammation in disease pathophysiology. Notably, a robust diagnostic panel comprising 11 proteins and 2 endogenous metabolites was established, achieving excellent classification performance (AUC of 0.96). To our knowledge, the integrated application of salivary proteomics and metabolomics for COPD diagnosis remains largely unexplored, underscoring the significance and translational potential of our findings.

Humans↗
PubMed2026

Genome-resolved analysis reveals disruption of gut microbial vitamin B and K2 biosynthesis during Toxoplasma gondii infection in mice.

UNLABELLED: Toxoplasma gondii infection remodels the gut microbiome, yet its impact on microbial vitamin biosynthetic potential and host redox metabolism remains unclear. Here, we integrated mouse gut metagenomes with publicly available metagenome-assembled genomes (MAGs) to construct a genome-resolved atlas of B-vitamin and vitamin K2 biosynthesis. From 45,697 MAGs, we curated 4,771 representative genomes, of which 2,682 met high-quality criteria (completeness &#x2265;90%, contamination <5%). Functional annotation identified 229,717 vitamin-related genes corresponding to 177 Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologs across de novo pathways for eight B vitamins, thiamine (B1), riboflavin (B2), niacin (B3), pantothenate (B5), pyridoxine (B6), biotin (B7), folate (B9), cobalamin (B12), and vitamin K2. Among the high-quality genomes, 1,665 encoded complete de novo pathways for at least one vitamin, highlighting functional specialization and community-level complementarity. Transcripts per million-normalized metagenomic read counts revealed significant differences in KEGG ortholog abundances across six of the nine vitamin pathways. Reanalysis of metagenomic data from infected mice (acute, chronic, and control; n = 10 per group) revealed a stage-dependent reduction in &#x3b1;-diversity of vitamin biosynthesis pathways during acute infection, and a clear &#x3b2;-diversity separation from chronic and control groups. Core niacin biosynthesis genes (nadB, nadA, nadC) displayed phylum-specific redistribution, indicating selective remodeling of microbial NAD+ precursor production under infection-induced metabolic stress. These results suggest that T. gondii infection disrupts cooperative vitamin biosynthetic networks while specifically modulating niacin pathways linked to host NAD+ metabolism. IMPORTANCE: Gut microbes can synthesize essential vitamins, but how infection alters this function is poorly understood. By integrating mouse gut metagenomes with genome-resolved microbial data, we show that Toxoplasma gondii infection reshapes the vitamin biosynthetic potential of the gut microbiome in a stage-dependent manner. Acute infection reduces the diversity of vitamin biosynthesis pathways and shifts the taxonomic distribution of key niacin biosynthesis genes involved in microbial NAD+ precursor production. These findings identify vitamin metabolism, especially niacin-related pathways, as a sensitive functional axis of microbiome remodeling during infection. Our work links microbial taxonomic changes to functional metabolic consequences and suggests that microbiome-mediated regulation of NAD+-related metabolism may contribute to host redox adaptation during T. gondii infection.

B vitamins↗
PubMed2025

The impact of Iso-mukaadial acetate on Plasmodium falciparum transcriptional gene regulation.

Malaria remains prevalent globally despite various intervention strategies aimed at preventing its transmission. With the decreasing effectiveness of antimalarial drugs, medicinal plant extracts have been proposed as alternatives. Iso-mukaadial acetate extracted from Warburgia salutaris has shown anti-plasmodial activity, but the mechanism of inhibition is unknown. In this study, RNA sequencing analysis of P. falciparum NF54 strain treated with IMA was conducted to determine the possible targets of IMA. The expression profiles of P. falciparum genes regulated by IMA and chloroquine (antimalarial control) during the intraerythrocytic stage were analyzed with gene ontology tools, including PlasmoDB, ShinyGO and g: Profiler. IMA and chloroquine upregulated genes linked to parasite biological processes and cell adhesion molecular binding functions, including PfEMP1, RIFIN, and STEVOR. Chloroquine specifically downregulated DNA replication processes involving DNA replication licensing factors MCM3 and DNA helicase, while IMA downregulated peptidyl-proline modification and glycolytic pathways. KEGG analysis suggested glycolysis-gluconeogenesis and pentose phosphate pathway enzymes (e.g., glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glucose-6-phosphate dehydrogenase (G6PD)-6-phosphogluconolactonase) as theoretical IMA targets, whose suppression could hypothetically reduce ATP and NADPH production, weakening parasite energy supply and antioxidant defenses. The inhibition of DNA replication components (MCM complex, DNA topoisomerases) by IMA, and the downregulation of DNA replication/repair proteins by chloroquine, may both impair genome integrity, contributing to the observed anti-plasmodial effects. IMA treatment was assumed to be associated with impairment of parasite energy metabolism, redox balance and DNA replication machinery. These effects differ from chloroquine, which primarily targeted DNA replication and repair processes, yet both drugs upregulated adhesion-associated gene families. Changes in the expression of metabolic and replication genes induced by IMA suggest the compounds potential as an anti-plasmodial candidate, warranting further biochemical validation of its mechanism of effect.

Plasmodium falciparum↗
PubMed2026

Multi-omics identification of therapeutic targets of compound sappan decoction in hepatocellular carcinoma.

BACKGROUND: Compound sappan decoction (CSD) is a multi-herbal traditional Chinese medicine formulation with clinical relevance in hepatocellular carcinoma (HCC). However, its therapeutic mechanisms remain unclear. METHODS: Bioactive compounds of CSD were identified and standardized using pharmacological and chemical databases. Potential targets were predicted via multiple target inference platforms. HCC-related genes were curated from comprehensive disease databases. Summary-data-based Mendelian randomization (SMR) was conducted to infer causal relationships between compound targets and HCC risk using large-scale quantitative trait loci (QTL) datasets and HCC genome-wide association study data. Colocalization analysis, protein-protein interaction (PPI) network construction, and GO/KEGG enrichment were performed on SMR-identified targets. Molecular docking evaluated binding affinities of representative compounds to prioritized targets. RESULTS: A total of 784 overlapping genes between predicted CSD targets and HCC-related genes were subjected to SMR analysis. Among these, 22 targets were significantly associated with HCC risk based on transcriptomic or proteomic QTLs and showed colocalization evidence. Notably, four targets (ADRB2, APOE, SYK, and PGF) were supported by both replication in an independent cohort and strong colocalization. These 22 targets were enriched in apoptosis, PI3K-Akt signaling, redox metabolism, and detoxification pathways. PPI analysis revealed central hubs including MMP9, BCL2, CASP1, and MCL1. Molecular docking demonstrated strong binding of APOE to quercetin, PGF to luteolin-7-olate, and SYK to kaempferol. CONCLUSIONS: CSD may exert therapeutic effects on HCC through modulation of genetically validated targets involved in tumor progression, inflammation, and metabolic reprogramming, supporting its potential clinical utility as an adjunctive treatment strategy. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s12672-026-04740-8.

Caesalpinia↗
PubMed2026

Metagenome-resolved evidence that soluble factors in granular activated carbon-amended reactor effluent reprogram propionate metabolism and methanogenic pathways.

Granular activated carbon (GAC) enhances anaerobic digestion performance, yet the mechanisms underlying reactor-scale improvements remain incompletely understood, particularly how GAC affects biomass not attached to its surface. Here, sludge from a non-GAC up-flow anaerobic sludge blanket reactor was incubated with 0.45-&#x3bc;m-filtered effluents from non-GAC and GAC-amended reactors under repeated propionate loading, followed by genome-resolved metagenomics. GAC-reactor effluent increased methane yield from 64&#x202f;&#xb1;&#x202f;3% to 76&#x202f;&#xb1;&#x202f;3% (p&#x202f;<&#x202f;0.01) in the absence of GAC particles. A non-redundant catalog of 170 quality-filtered metagenome-assembled genomes (MAGs) was recovered, enabling pathway- and gene-set quantification. Genomic potential for both major propionate-oxidation routes increased in the GAC-effluent group relative to the non-GAC group, with a larger increase for the methylmalonyl-CoA (MMC) route than for the dismutation route (1.289- versus 1.221-fold). Accordingly, the MMC-to-dismutation preference ratio was 5.60% higher in the GAC-effluent group, alongside a broader carrier base. Cobamide potential shifted toward remodeling and cobamide-dependent use rather than increased de novo corrin-ring synthesis. Candidate electron-transfer architectures were also rebalanced: PilA-associated carriers became less prominent, whereas maturation-supported multiheme cytochrome carriers increased from 22.96% to 34.90% of community abundance, although H2/formate-module carriers remained prevalent. Quorum-sensing systems underwent pathway- and carrier-specific redistribution, while all eight curated extracellular-polysaccharide modules showed higher mean gene abundance in the GAC-effluent composite. These findings show that a filter-passing effluent fraction can extend GAC-associated effects beyond direct particle contact and link enhanced methanogenesis to a broader, redistributed network of metabolic, redox, and coordination capacities. This expands the mechanistic framework of conductive-material-assisted anaerobic digestion and provides a basis for harnessing GAC-derived functions throughout the reactor.

Extracellular polymeric substances (EPS)↗
PubMed2026

Unraveling anaerobic indole degradation in an acclimated sludge consortium: Candidate pathways and microbial division of labor inferred from metagenomic and metatranscriptomic analyses.

Indole is a widespread nitrogen-containing heterocyclic compound in manure, sludge, and wastewater systems, yet the enzymes and microbial populations involved in its anaerobic transformation remain poorly resolved. Here, we established a long-term acclimated anaerobic sludge consortium and combined degradation assays, metabolite profiling, metatranscriptomics, and genome-resolved metagenomics to investigate the functional basis of anaerobic indole degradation. After 120 days of acclimation, the consortium stably degraded 100&#x202f;mg/L indole, whereas skatole was not effectively removed under the same strategy, indicating substrate-specific adaptation of the microbial community. Metabolite profiling detected oxindole, dioxindole, isatin, and anthranilic acid, supporting a putative transformation route involving pyrrole-ring oxidation and ring cleavage toward anthranilate-like intermediates. Metatranscriptomic analysis identified 16,660 differentially expressed genes after indole addition, with strong transcriptional responses involving oxidoreductases, hydrolases, cofactor-dependent redox metabolism, aromatic-CoA-related metabolism, and methane metabolism-associated pathways. Transcriptional responses highlighted the xanthine dehydrogenase-like molybdenum-enzyme system and isatin hydrolase as candidate contributors to upstream indole transformation, whereas those of abmG-like, bcrC, and oah genes were consistent with possible anthranilic acid activation and downstream CoA-type processing. MAG-resolved analysis further suggested that these candidate functions may be distributed among populations affiliated with Bacteroidota, Chloroflexota, Desulfobacterota, and Methanobacterium. Together, these findings establish a stable anaerobic indole-degrading consortium and provide a testable functional framework for syntrophic interactions linking upstream indole transformation, aromatic-CoA metabolism, and methanogenesis-associated carbon flow.

Anaerobic degradation↗
PubMed2026

Proteomic characterization of ocular tear fluid reveals preclinical markers of sulfur mustard toxicity.

Sulfur mustard (SM) vapor causes ocular injury after a short latent period, when molecular damage has occurred, but clinical signs are not yet apparent. Characterizing ocular responses during this early phase is important for understanding SM pathogenesis, identifying molecular readouts of injury progression, and developing biomarkers of exposure. Tear fluid is well-suited for this purpose because it can be collected noninvasively and captures responses from injured ocular tissues. We tested whether temporal changes in the tear fluid proteome reflect cellular and molecular responses to corneal SM exposure. Rabbits were exposed to SM vapor using a corneal vapor cap, and tear fluid was collected at baseline, 4&#x2009;h, 1 d, and 5 d, corresponding to the latent period, acute lesion, and early recovery. A large proteomic response was detected at 4&#x2009;h, involving extracellular injury signaling, epithelial injury, and innate immune activation. By 1 d, the tear fluid proteome transitioned to inflammatory cell activation with metabolic, redox, and proteostasis stress. By 5 d, evidence of acute injury response was reduced but the proteome retained a residual signature of immune, epithelial, and stress responses. This temporal progression is consistent with the molecular mechanisms of SM toxicity and provides insight into acute ocular vesicant injury. These findings establish tear fluid as a noninvasive molecular reporter of ocular SM injury progression. They also reveal a molecular signature of vesicant exposure, which emerges prior to clinical signs, and provide foundational data for developing tear-based biomarkers of chemical exposure, injury assessment, and therapeutic testing.

Animals↗
PubMed1976

Effect of haematocrit value and pO2 on the redox state and metabolism of the perfused liver.

1. The haematocrit value and pO2 of blood perfusing the isolated liver were varied. Provided O2 content of the blood was not rate-limiting, O2 consumption was related to haemotocrit value rather than O2 saturation or pO2. 2. Hypoxia caused the blood-glucose concentration and ketogenesis to increase and the output of very-low-density (d less than 1.006) lipoproteins to decrease. 3. A decrease in pO2 caused an increase in both the (lactate)/(pyruvate) and (3-hydroxybutyrate)/(acetoacetate) and a decrease in (ATP)/(ADP) ratios, independently of O2 consumption. 4. The more reduced redox state was associated with a shift in the balance between the oxidation and esterification of free fatty acids in favour of oxidation. 5. Acetoacetate may be an important hydrogen acceptor during hypoxia of the liver.

Acetoacetates↗
PubMed2018

Signaling Pathways Regulating Redox Balance in Cancer Metabolism.

The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells' demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions.

OXPHOS↗
PubMed1978

Metabolic adaptation to hypoxia. Redox state of the cellular free NAD pools, phosphorylation state of the adenylate system and the (Na+-K+)-stimulated ATP-ase in rat liver.

The effect of hypoxia (30 min 10% or 8% O2) on the phosphorylation state and redox state of the cytosol and mitochondria of rat liver were studied. Measurements were made both from normal animals and animals which had been exposed to the reduced partial pressure of oxygen (50.5 kPa or 40.8 kPa of air) for one or seven days. Cytostolic free NAD was reduced in the liver both in acute hypoxia and in hypoxia after one or seven days, i.e. the lactate/pyruvate and sn-glycerol-3-phosphate/dioxyacetonephosphate ratios increased markedly. A marked reduction in the mitochondrial free NAD pool occurred only in acute hypoxia and only a slight reduction was observed in animals kept at 40.8 kPa for one or seven days, as evaluated from the hepatic hydroxybutyrate/acetoacetate ratio. Liver ATP concentration decreased rapidly in acute hypoxia without any significant recovery during one or seven days at 40.8 kPa. The hepatic ATP/ADP X Pi ratio decreased significantly, with a simultaneous decrease in the total adenine nucleotide concentration. A tendency was observed for the ATP/ADP X Pi ratio to return to normal after seven days, i.e. the values in acute hypoxia were significantly smaller than those noted in hypoxia after seven days, demonstrating an adaptation of the energy metabolism during prolonged hypoxia. Hepatic (Na+-K+)-stimulated ATP-ase activity was not affected by hypoxia.

Acetates↗
PubMed2026

Integrating transcriptomics and metabolomics reveals the molecular landscape of sperm maturation driven by regional differentiation in the epididymis of Guizhou-Guiqian semi-fine wool sheep.

Epididymal regionalized differentiation is crucial for sperm maturation. However, little is known about the synergistic remodeling mechanisms of different epididymal segments at the transcriptional and metabolic levels during sexual maturation in ruminants (especially sheep). We investigated the caput, corpus, and cauda epididymidis of pre-pubertal (2-month-old) and post-pubertal (7-month-old) Guizhou-Guiqian semi-fine wool sheep using histology, RNA sequencing, and metabolomics. Post-pubertal tissues exhibited increased luminal diameters, cilia lengths, and abundant cauda spermatozoa. Transcriptomic analysis revealed increasing differentially expressed genes (DEGs) along the caput-corpus-cauda axis (4642, 6103, and 7698 DEGs, respectively). Metabolomics detected 786 unique differentially accumulated metabolites (DAMs). Region-specific analysis showed that in the caput, up-regulated pathways (fructose/mannose metabolism; HK2, ALDOA, HKDC1) provide energy and substrates for initial sperm motility. In the corpus, down-regulated genes associated with extracellular matrix and tight junctions suggested epithelial barrier remodeling to establish an immune-tolerant microenvironment. The cauda specifically up-regulated the pentose phosphate pathway (FBP1, GPI) and glutathione metabolism, maintaining redox homeostasis for long-term sperm storage. Additionally, glycerophospholipid metabolism was enriched across all segments, where PEMT, AGPAT5, and LCAT likely regulate sperm plasma membrane fluidity. In conclusion, during sexual maturation, the caput drives energy metabolism and glycosylation, the corpus establishes immune tolerance, and the cauda maintains antioxidant homeostasis. The glycerophospholipid network throughout the across all epididymal segments synergistically remodels sperm membrane. This study reveals the underlying multi-omics regulatory mechanisms of epididymal functional differentiation, providing a theoretical basis for elucidating the molecular mechanisms of sperm maturation in this breed and for the molecular breeding of early reproductive performance in rams.

Animals↗
PubMed1979

Redox potential-dependent nitrite metabolism by Salmonella typhimurium.

Salmonellae are generally resistant to the inhibitory effects of NaNO2. Removal of the lipopolysaccharide of Salmonella typhimurium by ethylenediaminetetraacetic acid pretreatment did not result in subsequent inhibtion of growth by NaNO2, indicating that lipopolysaccharide does not function to exclude NaNO2 from the cell. NaNO2 disappeared from the medium while the cells were growing, but, after stationary phase was reached, no further losses were observed unless the pH was maintained above 7.0. Similar losses were observed in a cell-free system if the redox potential of the medium was between -250 and -175 mV. If the disrupted cell suspension was first heated in a boiling water bath for 15 to 18 min, no NaNO2 loss was observed regardless of the redox potential. S. typhimurium is capable of metabolizing NaNO2, possibly by means of a nitrite-reducing enzyme function which is redox controlled.

Drug Resistance, Microbial↗
PubMed1979

Investigation of the significance of a carbon and redox balance to the measurement of gaseous metabolism of Saccharomyces cerevisiae.

A complete carbon and redox balance for Saccharomyces cerevisiae grown in batch culture with ethanol as the limiting carbon and energy source is reported. A novel method, which allowed the determination of carbon dioxide contained in the culture medium and biomass, is described and revealed amounts considerably in excess of what was expected from equilibrium data. Furthermore, elemental composition of the biomass was used to calculate the amount of oxygen required for biosynthetic reactions. When these corrections are applied to experimentally measured gas metabolism data, apparently anomalous results are shown to be consistent with the overall metabolism of bakers' yeast. These findings have wide implications to the quantitative study of the metabolism and energetics of facultative aerobes.

Carbon↗