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Cofactors and cosubstrates of intermediary metabolism that are involved in chromatin regulation. Note that the schematic representation of key metabolic pathways is simplified. To emphasize the steps discussed in the text, we omitted multiple steps and connections between pathways. (3-PG) 3-phosphoglycerate; (3-P-PYR) 3-phosphopyruvate; (3-P-Ser) 3-phosphoserine; (THF) tetrahydrofolate; (10-fTHF) N 10 -formyl-THF; (ac) acetyl; (Ac-CoA) acetyl-CoA; (Acet.) acetate; (αKG) α-ketoglutarate; (ar) ADP-ribosyl; (βOHB) β-hydroxybutyrate ; (β-oxid.) β-oxidation; (but) butyrate; (CH 2 -THF) N 5 N 10 -methylene-THF; (CH 3 -THF) N 5 -methyl-THF; (cit) citrate; (FAD) Flavin adenine dinucleotide; (fum) fumarate; (HCO − 2 ) formate; (hCys) homocysteine; (icit) isocitrate; (JMJC) Jumonji C domain-containing demethylase ; (KMT) lysine methyltransferase; (lac) lactate; (LSD) lysine-specific demethylase; (Mal-CoA) malonyl-CoA; (me) methyl; (Met) methionine ; (NA) nicotinic acid; (NR) NAM riboside; (PARP) poly-ADP-ribose polymerase; (pep) phosphoenolpyruvate; (pyr) pyruvate; (PRMT) protein arginine methyltransferase; (R-2HG) R-enantiomer of 2-hydroxyglutarate; (SAM) S-adenosylmethionine; (SAH) S-adenosylhomocysteine ; (suc) succinate; (TET) TET DNA demethylase; (Trp) tryptophan;(vit) vitamin.
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To make the appropriate developmental decisions or maintain homeostasis, cells and organisms must coordinate the expression of their genome and metabolic state. However, the molecular mechanisms that relay environmental cues such as nutrient availability to the appropriate gene expression response remain poorly understood. There is a growing awaren...
Citations
... The generated inosine monophosphate can be further catalyzed into xanthosine monophosphate by inosine monophosphate dehydrogenase, followed by production of guanosine-5′-monophosphate [38]. Van der Knaap and Verrijzer [39] reported that the inosine monophosphate dehydrogenase can accumulate in response to oxidative or replicative stress. As described in previous work, TB has been shown to effectively enhance the total antioxidant capacity by improving the activity of antioxidative enzymes [28]. ...
Simple Summary
Tributyrin has been used as a feed additive to modify the gastrointestinal microflora structure of ruminants, whereas its potential impact on meat quality characteristics has not been well characterized. To fully investigate its potential, an experiment was performed to evaluate the effects of supplementary tributyrin on the meat quality characteristics of foreshank muscle of weaned lambs. When tributyrin was added into the diets of weaned lambs, we found that the meat quality characteristics of foreshank muscle, such as its pH value, redness, water-holding capacity, and intermuscular fat accumulation, as well as its contents of both amino acids and fatty acids, were significantly influenced by supplementing tributyrin. The current research related to the effects of supplementing tributyrin on meat quality characteristics of foreshank muscle of weaned lambs could help with the intensification of nutritional strategies for tributyrin-based livestock systems, improving the meat quality.
Abstract
This experiment aimed to evaluate the effects of supplementing tributyrin (TB) on the meat quality characteristics of foreshank muscle of weaned lambs. A total of 30 healthy weaned Small-Tailed Han female lambs with body weights ranging from 23.4 to 31.6 kg were selected and randomly divided into five groups, and each group consisted of 6 lambs. The control group was fed a basic total mixed ration, while other groups were fed the same ration supplemented with 0.5, 1.0, 2.0, and 4.0 g/kg TB, respectively. The experiment lasted 75 d, including 15 d of adaptation. Foreshank muscle obtained at the same position from each lamb was used for chemical analysis and sensory evaluation. The results showed that supplementing TB increased the muscle contents of ether extract (p = 0.029), calcium (p = 0.030), phosphorus (p = 0.007), and intermuscular fat length (p = 0.022). Besides, TB increased the muscle pH (p = 0.001) and redness (p < 0.001) but reduced the lightness (p < 0.001), drip loss (p = 0.029), cooking loss (p < 0.001), shear force (p = 0.001), hardness (p < 0.001), cohesiveness (p < 0.001), springiness (p < 0.001), gumminess (p < 0.001), and chewiness (p < 0.001). In addition, TB increased the muscle content of inosine-5′-phosphate (p = 0.004). Most importantly, TB increased the muscle contents of essential amino acids (p < 0.001). Furthermore, TB increased the saturated fatty acids level in the muscle (p < 0.001) while decreasing the unsaturated fatty acids content (p < 0.001). In conclusion, supplementing TB could influence the meat quality of foreshank muscle of weaned lambs by modifying the amino acid and fatty acid levels.
... PGCs are specified as early as E7.5, i.e. mid-gastrulation and as the development proceeds, they migrate to the genital ridge and differentiate according to sex [58]. During their development, PGCs undergo various epigenetic changes, and it is known that epigenetic changes are linked to metabolic pathways that provide methyl, acetyl, etc. groups to modify the histone and the DNA, thus regulating gene expression in these cells [59,60]. However, very little is known about the metabolic signature of the PGCs. ...
Metabolic networks are well placed to orchestrate the coordination of multiple cellular processes associated with embryonic development such as cell growth, proliferation, differentiation and cell movement. Here, we discuss the advantages that gastruloids, aggregates of mammalian embryonic stem cells that self-assemble a rudimentary body plan, have for uncovering the instructive role of metabolic pathways play in directing developmental processes. We emphasise the importance of using such reductionist systems to link specific pathways to defined events of early mammalian development and their utility for obtaining enough material for metabolomic studies. Finally, we review the ways in which the basic gastruloid protocol can be adapted to obtain specific models of embryonic cell types, tissues and regions. Together, we propose that gastruloids are an ideal system to rapidly uncover new mechanistic links between developmental signalling pathways and metabolic networks, which can then inform precise in vivo studies to confirm their function in the embryo.
... The process of ATP hydrolysis causes the accumulation of hydrogen ions and a shift in the pH of the sarcolemma of muscle fibers to the acidic side, which is associated with rapid fatigue during intense physical activity due to the parallel formation of lactate in skeletal muscles, which is the end product of anaerobic glycolysis. Low lactate clearance leads to an increase in osmotic pressure, resulting in water entering the muscle fibers, swelling of the muscle fibers with subsequent compression of muscle pain receptors [16], [17]. ...
When performing maximum loads, an important criterion for assessing prospects is the achievement of the best result with the least metabolic changes in the body of athletes, which indicates the possibility of further increasing physical performance. The study of the mechanisms of energy supply and the reaction of body systems when testing performance under special conditions is one of the important conditions for the development of additional biochemical criteria for assessing the prospects of athletes. Purpose: To study genetic and physiological predictors of bioenergetic adaptation of skeletal muscles in athletes of cyclic sports. Methods: 76 athletes of cyclic sports (speed skating, running disciplines in track-and-field) of European origin who lived in the Southern Urals region took part in the study. The average age of the study participants was 22.1 ± 2.5 y.o. Experience in sports was at least 5 years. We used the Step One Real-Time PCR System (Applied Biosystems, USA) device for real-time polymerase chain reaction. The study of bio-energetic indicators of athletes' physical performance was carried out using the bicycle ergometry method (test with maximum load). Biochemical studies were carried out using a Lactate Scout Plus lactometer. Results: Significant differences were found in the ΔLa (%) indicator: in athletes with a dominant homozygous genotype R/R, lactate clearance during a 10-minute rest after performing a bicycle ergometer load is statistically significantly higher than in athletes with a recessive homozygous genotype X/X (20.14±12.74%, versus 11.11±3.12%; p<0.05). The major allele C (R) was associated with moderate and high lactate clearance (OR = 2.25 [95% CI: 0.99 – 5.11] and OR = 2.24 [95% CI: 0.91 – 5.51], respectively). At the same time, a statistically significant association was identified between the minor allele T(X) and the homozygous genotype TT (XX) with low lactate clearance (OR = 12.14 [95% CI: 1.30 – 13.55]). High values of lactate clearance indicate the utilization of lactate from peripheral blood and more efficient recovery processes in carriers of the major allele C (R). Conclusions: lactate clearance during a 10-minute rest period after a bicycle ergometer test with maximum load and DNA profiling of the ACTN3 gene rs1815739 can be recommended as significant physiological and genetic predictors of bioenergetic adaptation of skeletal muscles in cyclical sports athletes of Caucasian origin in the Southern Urals.
... Besides local fast-acting flux adjustment, global metabolic homeostasis is achieved through transcriptional regulation 9,[26][27][28][29][30] , which accounts for the majority (about 70%) of the changes in gene expression between growth conditions 29 . The gene expression profiles are primarily regulated by the global growth state via the sequestration or release of transcription factors (TFs) with the variation in the concentration of growth indicator metabolites 28,29 , as shown in the activities of over 200 TFs showing strong correlations with few cognate metabolites following the transition from starvation to growth in E. coli 9 . ...
... Step 2: The optimal strategy of the linearized kinetic model. In this section, we sought the simplified Eq. (27) representation based only on the associated metabolite concentrations. Firstly, we took the negative logarithmic operation of both sides of the Eq. ...
... Firstly, we took the negative logarithmic operation of both sides of the Eq. (27) and reorganized the right-hand terms: ...
Genome-scale metabolic networks (GSMs) are fundamental systems biology representations of a cell’s entire set of stoichiometrically balanced reactions. However, such static GSMs do not incorporate the functional organization of metabolic genes and their dynamic regulation (e.g., operons and regulons). Specifically, there are numerous topologically coupled local reactions through which fluxes are coordinated; the global growth state often dynamically regulates many gene expression of metabolic reactions via global transcription factor regulators. Here, we develop a GSM reconstruction method, Decrem, by integrating locally coupled reactions and global transcriptional regulation of metabolism by cell state. Decrem produces predictions of flux and growth rates, which are highly correlated with those experimentally measured in both wild-type and mutants of three model microorganisms Escherichia coli , Saccharomyces cerevisiae , and Bacillus subtilis under various conditions. More importantly, Decrem can also explain the observed growth rates by capturing the experimentally measured flux changes between wild-types and mutants. Overall, by identifying and incorporating locally organized and regulated functional modules into GSMs, Decrem achieves accurate predictions of phenotypes and has broad applications in bioengineering, synthetic biology, and microbial pathology.
... Emerging evidence indicates that chromatin modifications are determined by cell metabolic status, which then affects gene expression and cell fates [6][7][8] . Cell metabolism can impact on chromatin modifications via the activity of metabolic enzymes and metabolites 9 . Several metabolites serve as substrates for chromatin modifications, such as acetyl-CoA for acetylation, S-adenosylmethionine (SAM) for methylation, and ATP for phosphorylation 10,11 . ...
How cells adapt their gene expression to nutritional changes remains poorly understood. Histone H3T11 is phosphorylated by pyruvate kinase to repress gene transcription. Here, we identify the protein phosphatase 1 (PP1), Glc7 as the enzyme that specifically dephosphorylates H3T11. We also characterize two novel Glc7-containing complexes and reveal their roles in regulating gene expression upon glucose starvation. Specifically, the Glc7–Sen1 complex dephosphorylates H3T11 to activate the transcription of autophagy-related genes. The Glc7–Rif1–Rap1
complex dephosphorylates H3T11 to derepress the transcription of telomere-proximal genes. Upon glucose starvation, Glc7 expression is up-regulated and more Glc7 translocates into the nucleus to dephosphorylate H3T11, leading to induction of autophagy and derepressed transcription of telomere-proximal genes. Furthermore, the functions of PP1/Glc7 and the two Glc7-containing complexes are conserved in mammals to regulate autophagy and telomere structure. Collectively, our results reveal a novel mechanism that regulate gene expression and chromatin structure in response to glucose availability.
... Cells follow a strict mechanism to regulate metabolic fluxes to maintain metabolic homeostasis [140]. This involves the regulation of gene expression, mRNA transcription and translation, and the expression of transporter proteins and metabolic enzymes in response to extracellular factors such as hormones and intertissued signals [141]. In this way, metabolic activities and pathways are regulated to support desired physiological functions. ...
Treatment of large bone defects represents a great challenge in orthopedic and craniomaxillofacial surgery. Traditional strategies in bone tissue engineering have focused primarily on mimicking the extracellular matrix (ECM) of bone in terms of structure and composition. However, the synergistic effects of other cues from the microenvironment during bone regeneration are often neglected. The bone microenvironment is a sophisticated system that includes physiological (e.g., neighboring cells such as macrophages), chemical (e.g., oxygen, pH), and physical factors (e.g., mechanics, acoustics) that dynamically interact with each other. Microenvironment-targeted strategies are increasingly recognized as crucial for successful bone regeneration and offer promising solutions for advancing bone tissue engineering. This review provides a comprehensive overview of current microenvironment-targeted strategies and challenges for bone regeneration and further outlines prospective directions of the approaches in construction of bone organoids.
... The microbial population of the digestive tract creates postbiotics, which have numerous biological functions, such as acting as direct gene expression regulators. These might potentially act as catalysts for molecular processes causing disease [44]. As was already mentioned, important postbiotics include SCFA, plasmalogens, teichoic acids, vitamins, peptides, and enzymes. ...
... Specific molecules, such as sclerostin, regulate bone formation and phosphate metabolism (S. Vimalraj, 2020;Uda et al., 2017). ...
The repair of bone defects resulting from high-energy trauma, infection, or pathological fracture remains a challenge in the field of medicine. The development of biomaterials involved in the metabolic regulation provides a promising solution to this problem and has emerged as a prominent research area in regenerative engineering. While recent research on cell metabolism has advanced our knowledge of metabolic regulation in bone regeneration, the extent to which materials affect intracellular metabolic remains unclear. This review provides a detailed discussion of the mechanisms of bone regeneration, an overview of metabolic regulation in bone regeneration in osteoblasts and biomaterials involved in the metabolic regulation for bone regeneration. Furthermore, it introduces how materials, such as promoting favorable physicochemical characteristics (e.g., bioactivity, appropriate porosity, and superior mechanical properties), incorporating external stimuli (e.g., photothermal, electrical, and magnetic stimulation), and delivering metabolic regulators (e.g., metal ions, bioactive molecules like drugs and peptides, and regulatory metabolites such as alpha ketoglutarate), can affect cell metabolism and lead to changes of cell state. Considering the growing interests in cell metabolic regulation, advanced materials have the potential to help a larger population in overcoming bone defects.
... Metabolomics and proteomics can help identify potential biomarkers of high aggressiveness in patients with BC [202][203][204]. Certain metabolic pathways may be associated with the regulation of chemosensitivity and immunotherapy in BC and may serve as potential biomarkers for identifying high-risk patients [205,206]. ...
Bladder cancer (BC) is a clinical challenge worldwide with late clinical presentation, poor prognosis, and low survival rates. Traditional cystoscopy and tissue biopsy are routine methods for the diagnosis, prognosis, and monitoring of BC. However, due to the heterogeneity and limitations of tumors, such as aggressiveness, high cost, and limited applicability of longitudinal surveillance, the identification of tumor markers has attracted significant attention in BC. Over the past decade, liquid biopsies (e.g., blood) have proven to be highly efficient methods for the discovery of BC biomarkers. This noninvasive sampling method is used to analyze unique tumor components released into the peripheral circulation and allows serial sampling and longitudinal monitoring of tumor progression. Several liquid biopsy biomarkers are being extensively studied and have shown promising results in clinical applications of BC, including early detection, detection of microscopic residual disease, prediction of recurrence, and response to therapy. Therefore, in this review, we aim to provide an update on various novel blood-based liquid biopsy markers and review the advantages and current limitations of liquid biopsy in BC therapy. The role of blood-based circulating tumor cells, circulating tumor DNA, cell-free RNA, exosomes, metabolomics, and proteomics in diagnosis, prognosis, and treatment monitoring, and their applicability to the personalized management of BC, are highlighted.
... As a result of epigenetic modifications, metabolic enzyme genes expressed differently might contribute to metabolic reprogramming, which is necessary for glucose metabolism, lipid metabolism, and amino acid metabolism [10]. In addition, research has indicated the direct involvement of the metabolome in genome regulation [11]. Metabolomics also serves as an input that influences genomic alteration to form a feedback loop [12,13]. ...
Background:
The metabolome is the best representation of cancer phenotypes. Gene expression can be considered a confounding covariate affecting metabolite levels. Data integration across metabolomics and genomics to establish the biological relevance of cancer metabolism is challenging. This study aimed to eliminate the confounding effect of metabolic gene expression to reflect actual metabolite levels in microsatellite instability (MSI) cancers.
Methods:
In this study, we propose a new strategy using covariate-adjusted tensor classification in high dimensions (CATCH) models to integrate metabolite and metabolic gene expression data to classify MSI and microsatellite stability (MSS) cancers. We used datasets from the Cancer Cell Line Encyclopedia (CCLE) phase II project and treated metabolomic data as tensor predictors and data on gene expression of metabolic enzymes as confounding covariates.
Results:
The CATCH model performed well, with high accuracy (0.82), sensitivity (0.66), specificity (0.88), precision (0.65), and F1 score (0.65). Seven metabolite features adjusted for metabolic gene expression, namely, 3-phosphoglycerate, 6-phosphogluconate, cholesterol ester, lysophosphatidylethanolamine (LPE), phosphatidylcholine, reduced glutathione, and sarcosine, were found in MSI cancers. Only one metabolite, Hippurate, was present in MSS cancers. The gene expression of phosphofructokinase 1 (PFKP), which is involved in the glycolytic pathway, was related to 3-phosphoglycerate. ALDH4A1 and GPT2 were associated with sarcosine. LPE was associated with the expression of CHPT1, which is involved in lipid metabolism. The glycolysis, nucleotide, glutamate, and lipid metabolic pathways were enriched in MSI cancers.
Conclusions:
We propose an effective CATCH model for predicting MSI cancer status. By controlling the confounding effect of metabolic gene expression, we identified cancer metabolic biomarkers and therapeutic targets. In addition, we provided the possible biology and genetics of MSI cancer metabolism.
