Search Results (329)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency, the most common enzymatic disorder, affects over 500 million people worldwide and is often linked to exercise intolerance due to oxidative stress, but its true impact on physical performance remains unclear. This study aimed to evaluate the physiological and metabolic effects of G6PD deficiency on endurance capacity. Using humanized mice carrying the African G6PD variant [V68M; N126D] (hG6PD_A−), we show that despite reduced pentose phosphate pathway activity, these mice exhibit a 10.8% increase in treadmill critical speed (CS)—suggesting enhanced endurance capacity. Multi-omics profiling across red blood cells, plasma, skeletal muscle, spleen, kidney, and liver reveals metabolic adaptations, including elevated glycolysis, fatty acid oxidation, and increased mitochondrial activity, alongside heightened oxidative phosphorylation in muscle and accelerated red blood cell turnover in the spleen and liver. These findings indicate that systemic metabolic reprogramming may offset antioxidant deficiencies, potentially conferring a performance advantage. Given that G6PD deficiency affects up to 13% of African Americans and is associated with cardiovascular health disparities, our results challenge conventional exercise restrictions and highlight the need for personalized exercise guidelines for affected individuals. Full article

This study aimed to investigate the effects of adding 360 mg/kg niacinamide (NAM) to diets on nutrient metabolism, providing insights into how dietary NAM supplementation enhances nitrogen utilization and growth performance in pigs. Forty growing–finishing pigs were randomly assigned to one of four experimental diets as follows: basal diet + 30 mg/kg NAM (CON), basal diet + 360 mg/kg NAM (CON + NAM), low-protein diet + 30 mg/kg NAM (LP), and low-protein diet + 360 mg/kg NAM (LP + NAM). Results showed that supplementation of both the CON and LP diets with 360 mg/kg NAM resulted in decreased urea nitrogen concentrations and carbamyl phosphate synthetase-I activity (p < 0.05). The pyruvate dehydrogenase activity in the serum and liver, as well as the activity of pyruvate dehydrogenase, citrate synthase, and glutamate dehydrogenase 1 in the ileum mucosa, was increased by supplementing the LP diet with 360 mg/kg NAM (p < 0.05). The LP diet with 360 mg/kg NAM increased the villi length to crypt depth, mRNA expression of glucose transporters 1 and 2 and alanine-serine-cysteine transporter 1, and mRNA expression of mechanistic target of the rapamycin 1 in the ileum (p < 0.05). Additionally, 360 mg/kg NAM supplementation in the LP diet reduced ileal Lactobacillus abundance (LDA > 4) and increased ileal microbial nucleotide and purine metabolism (p < 0.05). Our findings suggest that addition of 360 mg/kg NAM to the LP diet reduced urea production in the liver, enhanced glucose and amino acid absorption and transport in the ileum, and improved glucose metabolism. Full article

Trypanosoma cruzi is a kinetoplastid parasite and etiological agent of Chagas disease. Given the significant morbidity and mortality rates of this parasitic disease, possible treatment alternatives need to be studied. 3-Bromopyruvate (3-BrPA) is a synthetic analog of pyruvate that was introduced in the early 21st century as an anticancer agent, affecting the proliferation and motility of certain microorganisms. Therefore, this work aims to evaluate the role of 3-BrPA in the energy metabolism, proliferation, and infectivity of T. cruzi, with a primary focus on the mitochondrial state, ATP production, and the key glycolytic pathway enzymes. It was observed that mitochondrial function in 3-BrPA cells was impaired compared to control cells. Accordingly, cells maintained in control conditions have a higher intracellular ATP content than cells maintained with 3-BrPA and higher ecto-phosphatase activity. However, the 3-BrPA reduced ecto-nuclease activity and was capable of hydrolyzing 5′-AMP, ADP, and ATP. When we evaluated two key glycolytic pathway enzymes, glucose kinase (GK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we observed that 3-BrPA induced higher GAPDH activity but did not alter GK activity. The compensatory energy mechanisms presented in T. cruzi may influence the process of cell metabolism and, consequently, the functional infectious process, suggesting the potential use of 3-BrPA in future clinical applications for Chagas disease. Full article

Nitrite is a common pollutant in aquaculture systems and can pose serious threats to fish health, especially under high-temperature conditions. This study aimed to investigate the impact of nitrite stress on the growth, glycolipid metabolism, and hepatic metabolomic profiles in the spotted seabass fry (Lateolabrax maculatus) under elevated temperature conditions at 33 °C. A total of 450 fish (28.52 ± 0.84 g) were randomly distributed into nine tanks and exposed to three nitrite concentrations (0, 8, and 16 mg/L), with samples collected on days 1, 3, 7, 14, 21, and 28. Results showed that higher nitrite levels significantly reduced final body weight, weight gain, survival rate, hepatosomatic index, and viscerosomatic index. Blood glucose and triglyceride levels, whole-body crude lipid, liver total cholesterol, and hepatic glycogen content also declined significantly under higher nitrite stress. In contrast, hepatic lactate and lactate dehydrogenase increased in the high-nitrite group. Gene expression analysis revealed suppressed lipid synthesis and enhanced lipolysis under nitrite exposure. Metabolomic analysis further demonstrated disruptions in key energy-related pathways, including the TCA cycle, pentose phosphate pathway, and insulin signaling. These findings indicate that nitrite stress impairs growth and energy metabolism in spotted seabass, which respond by mobilizing energy reserves to cope with combined stress of high temperature and nitrite. Full article

Glucose-6-phosphate dehydrogenase (G6PDH) is a critical enzyme in the pentose phosphate pathway, playing an essential role in plant growth, development, and adaptation to abiotic stress. In this study, we identified four members of the G6PDH gene family in the ‘Zunla-1’ genome, designating them as CaG6PDH1-CaG6PDH4. Multiple sequence alignment revealed that the four protein sequences of pepper contain three unique binding sites characteristic of G6PDH: the substrate binding site, the NADP binding site and the Rossmann fold. The phylogenetic tree, motifs, and gene structure analysis indicate that the CaG6PDH gene sequence is relatively conserved and structurally similar, with a close relationship to the sequence of Solanaceae G6PDH members. The collinearity analysis showed that there were two pairs of collinearity between the CaG6PDH genes and the AtG6PDH genes, as well as the SiG6PDH genes. Additionally, numerous cis-elements associated with stress responses, hormone regulation, development, and light responses were identified in the promoter region of the CaG6PDH gene. Furthermore, the various members of the pepper CaG6PDH gene family exhibit specific expression patterns across different tissues and demonstrate significant variations in response to abiotic stress and phytohormone treatments, particularly the CaG6PDH1 and CaG6PDH2 genes. Subcellular localization studies indicate that CaG6PDH2 is located in chloroplasts. We conducted further investigations into the role of CaG6PDH2 in response to cold stress using Virus-Induced Gene Silencing (VIGS) technology. The tissues of seedlings with silenced CaG6PDH2 exhibited significant damage and displayed a more pronounced cold damage phenotype. This observation is further supported by the accumulation of reactive oxygen species (ROS), the activity of antioxidant enzymes, and a reduction in the expression of cold-responsive genes. In conclusion, the findings of this study indicate that CaG6PDH2 plays an important role in cold stress response and may serve as a potential gene for cultivating cold-tolerant pepper varieties. Full article

Sub-optimal light environments in controlled agricultural settings often limit the productivity of plants. While LED supplementary lighting has been widely adopted to mitigate light deficiencies, the spatial arrangement of LED light sources remains a critical but under-explored factor affecting plant physiological responses. In this study, we used the affiliation function method to comprehensively analyze the effects of four spatial LED supplementary lighting configurations—top-down lighting (T1), mid-canopy upward lighting (T2), mid-canopy downward lighting (T3), and bottom-up lighting (T4)—on the growth and photosynthetic performance of tomato plants. Our findings reveal that the T1 treatment significantly increased light absorption in the upper and middle leaves, enhanced photosynthetic efficiency, promoted the CO₂ assimilation rate, and elevated the activities of key Calvin cycle enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), fructose-1,6-bisphosphatase (FBPase), transketolase (TK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and fructose-1,6-bisphosphate aldolase (FBA). These changes led to improved carbohydrate metabolism and biomass accumulation. Additionally, the T4 treatment markedly enhanced photosynthetic activity in the lower leaves, increasing sugar metabolism-related enzyme activities, such as sucrose synthase (SS), sucrose phosphate synthase (SPS), acid invertase (AI), and neutral invertase (NI). Consequently, compared with the CK treatment, the T4 treatment significantly increased the accumulation of glucose, fructose, and sucrose, with increases of 47.36%, 27.61%, and 87.21%, respectively. Furthermore, LED supplementation regulated endogenous hormone levels, thereby promoting overall plant growth. This study highlights the importance of the spatial arrangement of LEDs in optimizing light distribution and enhancing plant productivity, providing valuable theoretical and practical insights for improving agricultural practices in controlled environments. Full article

Erythritol has been widely used in the food industry, which predominantly synthesizes it via microbial fermentation, in which Yarrowia lipolytica serves as the preferred candidate chassis strain. However, the wild-type strain of Y. lipolytica exhibits several limitations, including suboptimal industrial performance and elevated levels of by-products, which pose significant challenges in biomanufacturing processes. It is significant to understand the synthesis mechanism of erythritol for improving the capacity of erythritol production by Y. lipolytica. In this study, a mutant exhibiting high erythritol production and stable genetic performance was obtained via a combination of UV and atmospheric and room-temperature plasma mutagenesis. Some key genes related to erythritol production were identified through comparative transcriptome analysis of the mutant strain, revealing significant changes in their expression levels. Individual overexpression of the genes encoding ribose-5-phosphate isomerase, glucose-6-phosphate-1-epimerase, adenylate kinase, and alcohol dehydrogenase in Y. lipolytica Po1g enhanced erythritol production, demonstrating the critical role of each gene in erythritol production. This finding elucidates the molecular mechanism underlying the improved erythritol yield in the mutant strain. The Y. lipolytica mutant C1 produced 194.47 g/L erythritol in a 10 L fermenter with a productivity of 1.68 g/L/h during batch fermentation, surpassing the wild-type strain and reducing the cultivation time by 21 h. It is significant to understand the mechanism of erythritol synthesis for improving erythritol production and its application in industrial-scale production. Full article

Damp-heat diarrhea (DHD) in piglets presents as diarrhea and intestinal bleeding, significantly affecting both piglet health and the pig industry. Pulsatilla powder (PP), a herbal formulation composed of Pulsatilla, Rhizoma Coptidis, Phellodendron Bark, and Fraxini Cortex, has proven to be an effective treatment for DHD. Although the pentose phosphate pathway (PPP) has been associated with its therapeutic effects, the exact mechanism of action remains unclear. In this study, the DHD model in piglets was established to evaluate clinical symptoms, organ index, serum index, histological changes, colonic metabolites, and molecular mechanisms using techniques such as QPCR, ELISA, WB and metabolomics. PP improved intestinal health by restoring spleen and lung index, increasing LDL-C and HDL-C levels (HDL-C: p < 0.05), decreasing mRNA expression levels of IFN-γ and TNF-α mRNA (p < 0.01), and increasing MUC1 and MUC2 expression. Metabolomics analysis has identified 44 pathways, including pentose phosphate and glutathione pathways, and 132 differential metabolites have involved in DHD treatment. PP significantly reduced G6PD (p < 0.01), inhibited the pentose phosphate pathway, reduced NOX production (p < 0.01), and suppressed ROS production (p < 0.01). These effects alleviated oxidative stress and intestinal damage, demonstrating PP’s effectiveness in treating DHD by targeting critical enzymes and ROS levels. Full article

Crop rotation and microbial driving force significantly influence soil phosphorus (P) bioavailability and crop yield. However, differences in underlying microbial mechanisms in rotations remain unclear. We examined rice yield, P uptake, soil and microbial P contents, enzyme activity, and P functional genes over six years (2016–2022) to elucidate microbial mechanisms driving rice yield in rice–wheat (RW) and rice–oilseed rape (RO) rotations. RO significantly increased rice yield and plant P uptake by 9.17% and 20.70%, respectively, compared to RW. Soil total (TP) and available (AP) P contents were significantly lower (4.83% and 18.31%, respectively) under RO than RW, whereas microbial biomass phosphorus (MBP) and acid phosphatase activity (EP) were greater (39.40% and 128.45%, respectively). PICRUSt2 results revealed that RO increased phoA phoB (alkaline phosphatase), phnX (phosphonoacetaldehyde hydrolase [EC:3.11.1.1]), gcd (Quinoprotein glucose dehydrogenase [EC:1.1.5.2]), and ppaC (manganese-dependent inorganic pyrophosphatase) and decreased phnD (phosphonate transport system substrate-binding protein), ugpE (sn-glycerol 3-phosphate transport system permease protein), ugpA (sn-glycerol 3-phosphate transport system permease protein), and phnO ((aminoalkyl)phosphonate N-acetyltransferase [EC:2.3.1.280]) abundance. Random forest analysis showed that ppaC, phnD, gcd, and phnX were important for rice yield and plant P uptake. Partial least squares analysis revealed that RO indirectly increased rice yield by influencing MBP and affecting plant P uptake through P functional genes. Overall, RO improves rice yield and P bioavailability by altering P functional genes (ppaC, phnD, gcd, and phnX), providing new perspectives on crop–microorganism interactions and resource use efficiency. Full article

Glucose is the preferred carbon source for most cells. However, cells may encounter other carbon sources that can be utilized. How cells match their metabolic gene expression to their carbon source, beyond a general glucose repressive system (catabolite repression), remains little understood. By studying the effect of up to seven different carbon sources on Snf1 phosphorylation and on the expression of downstream regulated genes, we searched for the mechanism that identifies carbon sources. We found that the glycolysis metabolites glucose-6-phosphate (G6P) and glucose-1-phosphate (G1P) play a central role in the adaptation of gene expression to different carbon sources. The ratio of G1P and G6P activates analogue calcium signaling via the proton-exporter Pma1 to regulate downstream genes. The signaling pathway bifurcates with calcineurin-reducing ADH2 (alcohol dehydrogenase) expression and with Cmk1-increasing ZWF1 (glucose-6-phosphate dehydrogenase) expression. Furthermore, calcium signaling is not only regulated by the present carbon source; it is also regulated by past carbon sources. We were able to manipulate this ionic memory mechanism to obtain high expression of ZWF1 in media containing galactose. Our findings provide a universal mechanism by which cells respond to all carbon sources. Full article

Metabolic reprogramming in cancer cells involves changes in glucose metabolism, glutamine utilization, and lipid production, as well as promoting increased cell proliferation, survival, and immune resistance by altering the tumor microenvironment. Our study analyzes metabolic reprogramming in neoplastically transformed cells, focusing on changes in glucose metabolism, glutaminolysis, and lipid synthesis. Moreover, we discuss the therapeutic potential of targeting cancer metabolism, focusing on key enzymes involved in glycolysis, the pentose phosphate pathway, and amino acid metabolism, including lactate dehydrogenase A, hexokinase, phosphofructokinase and others. The review also highlights challenges such as metabolic heterogeneity, adaptability, and the need for personalized therapies to overcome resistance and minimize adverse effects in cancer treatment. This review underscores the significance of comprehending metabolic reprogramming in cancer cells to engineer targeted therapies, personalize treatment methodologies, and surmount challenges, including metabolic plasticity and therapeutic resistance. Full article

The prevalence of human intestinal helminth parasitic infections is extensive, with over half of the global population estimated to suffer from these infections. Traditionally, various plant species, including Ricinus communis L. (Euphorbiaceae), are used to treat helminth infections. In this study, ricinoleic acid was isolated from the base hydrolysate of the petroleum ether seed extract of R. communis using column chromatography and transformed into ricinoleic acid methyl ester through esterification. The extract, ricinoleic acid and its methyl ester were evaluated for their anthelmintic activities against the model organism Caenorhabditis elegans. The results revealed that at a concentration of 1 mg/mL, ricinoleic acid and its methyl ester killed 97.40% and 97.83% of C. elegans worms, respectively. Molecular docking studies of ricinoleic acid on succinate dehydrogenase (SDH), glucose-6-phosphate 1-dehydrogenase (G6PD), and tubulin beta-2 chain (TBB2C) revealed that ricinoleic acid has a more favorable interaction with succinate dehydrogenase (−5.408 kcal/mol) compared to glucose-6-phosphate 1-dehydrogenase (−3.758 kcal/mol) and tubulin beta-2 chain (−1.444 kcal/mol). Furthermore, Absorption, Distribution, Metabolism, and Excretion (ADME) analyses unveiled that ricinoleic acid adheres to Lipinski’s rule of five, positioning it as a potential compound to treat helminths. The current study demonstrated that R. communis seed oil possesses genuine anthelmintic activity against C. elegans, which is likely due to ricinoleic acid. Full article

Interactions between carbon and nitrogen metabolism are essential for balancing source–sink dynamics in plants. Frequent cold stress disrupts these metabolic processes in rice and reduces grain yield. Two rice cultivars (DN428: cold-tolerant; SJ10: cold-sensitive) were subjected to 19 °C low-temperature stress at full-heading for varying lengths of time to analyze the effects on leaf and grain metabolism. The objective was to track carbon–nitrogen flow and identify factors affecting grain yield. Low-temperature stress significantly reduced the activity of nitrate reductase (NR), glutamine synthetase (GS), glutamate synthase (GOGAT), glutamate dehydrogenase (GDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT), in functional leaves compared to the control. This reduction decreased nitrogen accumulation, inhibited chlorophyll synthesis, and slowed photosynthesis. To preserve intracellular osmotic balance and lessen the effects of low temperatures, sucrose, fructose, and total soluble sugar levels, as well as sucrose synthase (SS) and sucrose phosphate synthase (SPS) activities, surged in response to low-temperature stress. However, low-temperature stress significantly reduced the activity of adenosine diphosphate glucose pyrophosphorylase (AGPase), granule-bound starch synthase (GBSS), soluble starch synthase (SSS), and starch branching enzyme (SBE). At the same time, low-temperature stress reduced the area of vascular bundles and phloem, making it difficult to transport carbon and nitrogen metabolites to grains on time. The response of grains to low-temperature stress differs from that of leaves, with prolonged low-temperature exposure causing a gradual decrease in carbon and nitrogen metabolism-related enzyme activities and product accumulation within the grains. The insufficient synthesis of starch precursors and carbon skeletons results in significantly lower thousand-grain weight and seed-setting rates, ultimately contributing to grain yield loss. This decline was more pronounced in inferior grains compared to superior grains. Compared to SJ10, DN428 exhibited higher values across various indicators and smaller declines under low-temperature stress, suggesting enhanced cold-tolerance and a greater capacity to maintain grain yield stability. Full article

Malic enzyme 1 (ME1) plays a key role in promoting malignant phenotypes in various types of cancer. ME1 promotes epithelial–mesenchymal transition (EMT) and enhances stemness via glutaminolysis, energy metabolism reprogramming from oxidative phosphorylation to glycolysis. As a result, ME1 promotes the malignant phenotypes of cancer cells and poor patient prognosis. In particular, ME1 expression is promoted in hypoxic environments associated with hypoxia-inducible factor (HIF1) α. ME1 is overexpressed in budding cells at the cancer invasive front, promoting cancer invasion and metastasis. ME1 also generates nicotinamide adenine dinucleotide (NADPH), which, together with glucose-6-phosphate dehydrogenase (G6PD) and isocitrate dehydrogenase (IDH1), expands the NADPH pool, maintaining the redox balance in cancer cells, suppressing cell death by neutralizing mitochondrial reactive oxygen species (ROS), and promoting stemness. This review summarizes the latest research insights into the mechanisms by which ME1 contributes to cancer progression. Because ME1 is involved in various aspects of cancer and promotes many of its malignant phenotypes, it is expected that ME1 will become a novel drug target in the near future. Full article

Insects often rely on symbiotic bacteria and fungi for various physiological processes, developmental stages, and defenses against parasites and diseases. Despite their significance, the associations between bacterial and fungal symbionts in Apis mellifera are not well studied, particularly in the Philippines. In this study, we collected A. mellifera from two different sites in the Municipality of Bacnotan, La Union, Philippines. A gut microbiome analysis was conducted using next-generation sequencing with the Illumina MiSeq platform. Bacterial and fungal community compositions were assessed using 16S rRNA and ITS gene sequences, respectively. Our findings confirm that adult worker bees of A. mellifera from the two locations possess distinct but comparably proportioned bacterial and fungal microbiomes. Key bacterial symbionts, including Lactobacillus, Bombilactobacillus, Bifidobacterium, Gilliamella, Snodgrassella, and Frischella, were identified. The fungal community was dominated by the yeasts Zygosaccharomyces and Priceomyces. Using the ENZYME nomenclature database and PICRUSt2 software version 2.5.2, a predicted functional enzyme analysis revealed the presence of β-glucosidase, catalase, glucose-6-phosphate dehydrogenase, glutathione transferase, and superoxide dismutase, which are involved in host defense, carbohydrate metabolism, and energy support. Additionally, we identified notable bacterial enzymes, including acetyl-CoA carboxylase and AMPs nucleosidase. Interestingly, the key bee symbionts were observed to have a negative correlation with other microbiota. These results provide a detailed characterization of the gut microbiota associated with A. mellifera in the Philippines and lay a foundation for further metagenomic studies of microbiomes in native or indigenous bee species in the region. Full article