Search Results (241)

Oral squamous cell carcinoma (OSCC) represents a significant global health challenge characterized by high morbidity and mortality, frequently driven by therapeutic resistance and tumor aggressiveness. Metabolic reprogramming has emerged as a hallmark of OSCC, enabling tumor cells to sustain proliferation, survive under adverse microenvironmental conditions, and evade therapeutic stress. Recent advances in cancer metabolism have identified metabolic plasticity as a central determinant of OSCC progression and treatment failure, highlighting the need to integrate evidence on metabolic vulnerabilities and therapeutic opportunities. This narrative review aims to provide an updated overview of metabolic reprogramming in OSCC, with particular emphasis on the interplay between glycolysis, mitochondrial metabolism, glutamine metabolism, and fatty acid oxidation, and to discuss how these interconnected pathways may be therapeutically exploited. Although OSCC cells exhibit enhanced aerobic glycolysis, mitochondria remain functionally active and play critical roles in energy production, redox homeostasis, and metabolic adaptation. The therapeutic potential of targeting tumor metabolism is discussed, highlighting dichloroacetate (DCA) as a promising metabolic modulator capable of inhibiting pyruvate dehydrogenase kinase (PDK), restoring mitochondrial glucose oxidation, and partially reversing the glycolytic phenotype. The review also examines the current translational limitations of DCA, including toxicity, pharmacokinetic constraints, and compensatory metabolic adaptations that restrict its efficacy as a standalone therapy. Furthermore, potential synergistic strategies are explored, particularly the combination of DCA with paclitaxel, which enhances therapeutic efficacy through concurrent disruption of cytoskeletal integrity and metabolic homeostasis, thereby increasing cellular susceptibility to apoptosis and overcoming chemoresistance. Full article

Background/Objectives: Betanin (Bet), a natural compound, exhibits potent antioxidant and metabolic regulatory properties, yet its effect on cellular glucose utilization remains unclear. This study investigated, for the first time, the impact of Bet on glucose consumption and the activation of key carbohydrate–catabolic pathways in human erythrocytes. Methods: In vitro assays were performed to evaluate enzyme inhibition and activation. Human erythrocytes were incubated with Bet to assess glucose consumption. Enzyme activities were measured spectrophotometrically, and molecular docking was used to analyze binding interactions. Results: Our results demonstrate that Bet inhibits digestive enzymes in a dose-dependent manner, with maximal inhibition at 90 µg/mL for pancreatic lipase and 70 µg/mL for α-amylase, showing IC₅₀ values of 48.8 and 31.9 µg/mL, respectively, supported by strong binding affinities of −9.3 and −8.9 Kcal/mol. These interactions are stronger than those of orlistat (−6.9 Kcal/mol) and acarbose (−7.7 Kcal/mol). Bet also induced the activity of AMPK with an IC₅₀ of 1.83 µg/mL and a BE of −7.90 Kcal/mol, compared to the specific AMPK activator A-769662, which had an IC₅₀ of 1.29 µg/mL and a binding energy of −10.0 Kcal/mol. Consequently, Bet stimulated key glycolytic enzymes, reaching maximal activation (~62%) at 1.4 µg/mL for hexokinase (HK) and glucose-6-phosphate dehydrogenase (G6PD), and at 1.6 µg/mL for pyruvate kinase (PK), supported by binding energies of −7.2, −7.5, and −9.0 Kcal/mol and AC₅₀ values of 0.87, 0.98, and 0.91 µg/mL, respectively. Moreover, Bet enhanced key Krebs cycle enzymes (IDH, SDH, MDH, LDH) in a dose-dependent manner, with AC₅₀ values of 0.76, 0.80, 0.72, and 0.52 µg/mL and strong binding energies (−7.8, −7.8, and −8.4 Kcal/mol), reaching maximal activation near 1.4 µg/mL. Bet also increased glucose consumption by human erythrocytes. Conclusions: Bet enhances glucose utilization by inhibiting digestive enzymes and activating intracellular metabolic pathways, suggest potential metabolic regulatory effects. Full article

Agaricus bisporus (A. bisporus) is susceptible to rapid postharvest deterioration. Although elevated CO₂ (6%) delays senescence, the metabolic mechanisms remain unclear. In this study, untargeted and targeted metabolomic analyses were employed to explore these pathways in A. bisporus. The results revealed that elevated CO₂ treatment promoted glycolysis by upregulating Hexokinase (HK), Phosphofructokinase (PFK), and Pyruvate Kinase (PK), accumulating Glucose-6-phosphate (G-6-P) and Fructose-6-phosphate (F-6-P). Concurrently, elevated CO₂ treatment upregulated the expression of genes associated with the tricarboxylic acid (TCA) cycle and increased the enzymatic activities of Malate Dehydrogenase (MDH) and Fumarate hydratase (FUM). These changes led to the rapid consumption of key intermediate metabolites (Fumarate (Fum), Malate (Mal), and α-Ketoglutarate (α-KG)), collectively enhancing the efficiency of the TCA cycle. Furthermore, elevated CO₂ treatment significantly suppressed the activities of Glutamine Synthetase (GS) and Xanthine Oxidase (XOD), inhibiting the synthesis of Glutamine (Gln) and Pyroglutamate (pGlu) while promoting the accumulation of Hypoxanthine (Hx). This coordinated reprogramming of amino acid metabolism and purine metabolism contributed to improved energy efficiency and enhanced cellular integrity in postharvest A. bisporus. This study elucidates the specific mechanism by which elevated CO₂ levels regulate the postharvest energy metabolism of A. bisporus from a metabolomics perspective, providing a theoretical basis for developing strategies to control its postharvest quality. Full article

The aim of this preliminary study was to determine the effect of taurine on the expression of genes involved in glycolysis, oxidative phosphorylation, inflammation, autophagy, and regenerative activity in cultured peripheral blood mononuclear cells (PBMCs) and articular cartilage explants from patients with end-stage rheumatoid arthritis (RA). PBMCs and knee articular cartilage were obtained from 20 patients with RA (3 men and 17 women) aged 62.2 ± 10.9 years, with a mean disease duration of 17.5 years (range: 2–43), prior to arthroplasty. PBMCs and cartilage explants were cultured in the presence of 50 µM taurine. Gene expression was determined using real-time reverse transcriptase polymerase chain reaction (RT-PCR). Protein expression of the examined genes in PBMCs was quantified using ELISA. In the presence of 50 µM taurine PBMCs from patients with RA demonstrated a significant increase in the expression of genes encoding pyruvate kinase (PKM2), succinate dehydrogenase (SDHB), uncoupler of oxidation and phosphorylation (UCP2), ATP synthase (ATP5B), and unc-51-like kinase 1 (ULK1). At the same time a significant decrease in tumor necrosis factor (TNF)α and interleukin (IL)-1β expression was noted. In cartilage explants, taurine upregulated SDHB, UCP2, ULK1, and type 2 collagen gene (COL2A1), and decreased TNFα expression. We concluded that, under in vitro conditions, taurine can influence the expression of genes involved in glycolysis, oxidative phosphorylation, inflammation, autophagy, and regenerative processes in PBMCs and articular chondrocytes from patients with end-stage RA. Full article

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, underscoring the need to better understand cardiovascular physiology. A key aspect involves identifying regulatory molecules that govern metabolic shifts. Forkhead box protein O1 (FoxO1) has emerged as a potential regulator; however, its role and underlying mechanisms remain unclear. This study investigated FoxO1 in metabolic adaptation using Wistar rats divided into age groups (fetal, postnatal day 1, postnatal day 7, adult) and treatment groups (control, hypoxia, FoxO1 inhibitor, combination). Hypoxia (12–14% O₂) and FoxO1 inhibitor (AS1842856, 10 mg/kgBW/day) were administered accordingly. Parameters assessed included hypoxia inducible factor 1 α (HIF-1α), FoxO1 mRNA and protein, glucose transporter type 1 (GLUT1), glucose transporter type 4 (GLUT4), cluster of differentiation 36 (CD36), hexokinase, pyruvate dehydrogenase kinase isoform 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), lactic acid, malonyl-CoA, carnitine palmitoyltransferase 1 (CPT1), citrate synthase, cytochrome c, and adenosine triphosphate (ATP). ATP production increased with age, associated with higher FoxO1 expression and metabolic shifts. Hypoxia in fetal hearts reduced HIF-1α and FoxO1. FoxO1 inhibition elevated glycolytic and oxidative markers. In conclusion, FoxO1 regulates glycolysis and lipid metabolism, offering insights into cardiac adaptation to hypoxia and potential therapeutic strategies. Full article

Soil hypoxia caused by waterlogging severely restricts kiwifruit growth, and screening waterlogging-tolerant rootstocks and analyzing their mechanisms are of great significance for industrial development. In this study, waterlogging-tolerant Actinidia valvata ‘Shuixiu’ was used as the test material and Actinidia chinensis ‘Hongyang’ as the control. Waterlogging stress was simulated artificially, and physiological measurements combined with transcriptome sequencing were used to explore its waterlogging tolerance regulatory characteristics based on respiratory metabolism. The results showed that the waterlogging tolerance of ‘Shuixiu’ was significantly better than that of ‘Hongyang’. It upregulated sucrose synthase and α/β-amylase genes and inhibited the continuous up-regulation of trehalose-6-phosphate synthase genes, leading to significant accumulation of glucose-6-phosphate, a key glycolytic substrate. Some members of glycolytic key gene families, such as glucose-6-phosphate isomerase and phosphofructokinase, were upregulated in ‘Shuixiu’, which increased phosphoglycerate kinase activity and accumulated 3-phosphoglyceric acid and pyruvate, ensuring efficient conversion of carbon sources to ATP. Some members of core tricarboxylic acid cycle gene families, such as pyruvate dehydrogenase and citrate synthase, were upregulated in ‘Shuixiu’, with significantly higher pyruvate dehydrogenase activity and acetyl coenzyme A content, maintaining partial aerobic respiration capacity. Some members of the alanine transaminase gene family were upregulated in ‘Shuixiu’ to enhance alanine fermentation, resulting in a significant reduction in root ethanol accumulation. This study clarified the core respiratory metabolic regulatory characteristics of kiwifruit in response to waterlogging and provided key targets and a theoretical basis for molecular breeding of waterlogging-tolerant rootstocks. Full article

Hypoxia-dependent microRNAs play an important role in orchestrating a plant’s response to low-oxygen stress. To assess the regulatory mechanisms of the adaptive response of maize (Zea mays L.) to hypoxia, an antisense sequence was developed, and the short tandem target mimic (STTM) system was used to induce the loss of function of the mature microRNA775A (miR775a) in maize. A recombinant binary vector pBI121 cloned in E. coli cells containing the antisense sequence anti-miR775A to maize miR775A was acquired to create a line of modified A. tumefaciens EHA105. Using the puncturing method on soaked seeds, maize plants with an active anti-miR775A construct were obtained, as evidenced by a decrease of more than 10-fold in mature miR775A content and by developmental changes in the seedlings. The size of seedlings of the maize knockdown line was almost twice smaller than that of the wild-type (WT) plants. An assessment of the effects of hypoxic conditions induced by flooding of 14-day-old maize plants revealed differences in the expression and activity of several enzymes between WT and knockdown plants. The reduced miR775A levels led to a 2.1-fold drop in pyruvate levels, which resulted in decreased pyruvate kinase, pyruvate dehydrogenase, and lactate dehydrogenase activities as compared to WT plants. A decrease in miR775A content in the maize knockdown cell line also affected the function of mitochondrial and extramitochondrial isoenzymes of citrate synthase, aconitase, and fumarase under hypoxic conditions. Full article

Epstein–Barr virus (EBV) is a human pathogenic and oncogenic herpesvirus, with worldwide importance, at times associated with serious to life-threatening symptoms, especially in immunocompromised hosts. The available preventive options against EBV disease are limited to medically elaborate and cost-intensive measures of cell-based immunotherapy. The development of novel options of anti-EBV drug targeting is currently a matter of intense international efforts. A putative target of the antiviral therapy approach is the EBV-encoded protein kinase BGLF4, which fulfills a multifaceted role in productive viral replication. So far, viral BGLF4 interactor proteins and phosphorylated substrates have occasionally been reported, but in particular cellular interactors await further characterization concerning both, their relevance for BGLF4 functionality and their accessibility to antiviral drugs. In this study, we have analyzed host cell–BGLF4 interaction, BGLF4 kinase properties, and BGLF4-directed small molecules. The main results are as follows: (i) a mass spectrometry-based interactomic study was performed with EBV-producing Akata-BX1 cells, thereby identifying the human pyruvate dehydrogenase (PDH) as a relevant BGLF4 interactor; (ii) BGLF4–PDH interaction was confirmed by protein coimmunoprecipitation, subcellular cofractionation, and confocal imaging; (iii) the BGLF4-mediated phosphorylation of PDH was demonstrated by an in vitro kinase assay (IVKA); (iv) a reduction in PDH phosphorylation was shown for selected kinase inhibitors, which also exerted BGLF4-directed inhibitory potential in a quantitative qSox-IVKA, and (v) these hit compounds showed anti-EBV activity in lytically induced P3HR-1 cells using qPCR measurement, as well as PDH-inhibitory activity using standardized PDH assays. These data lead to an improved understanding of EBV–host interaction that may open novel anti-EBV preventive opportunities. Combined, the findings point to PDH as a new cellular interactor of the EBV kinase BGLF4. Also, notably, the data on pharmacological intervention with kinase activity or substrate phosphorylation may possibly provide as yet untapped options of antiviral drug targeting. Full article

The intensification of aquaculture often leads to dissolved oxygen depletion, posing a significant hypoxic stress to aquatic organisms such as the mudskipper (Boleophthalmus pectinirostris). Identifying compounds that can mitigate hypoxic damage is therefore of great importance. This study investigated the protective effects of puerarin and dexamethasone against acute hypoxic stress in mudskippers. Four experiment groups were formulated: fish in the control group (HC) and the hypoxia group (HH) were injected with NaCl, fish in the puerarin group (HP) were injected with puerarin, and fish in the dexamethasone group (HD) were injected with dexamethasone, then the HH, HP, and HD groups were treated with a hypoxia condition sustained for 48 h. Compared with the HC and HP groups, the HH group showed significantly reduced activities of protein kinase B (Akt), glycogen synthase kinase (GSK-3β), lactate dehydrogenase (LDH), and pyruvate kinase (PK) in the liver at 24 and 48 h. The gene transcription levels of GSK-3β and Akt in the liver and gill of mudskipper were the smallest, but p53, VEGF, HIF-1, and BNIP3 in the liver of fish in the HH group were significantly highest. The gene transcription levels of GSK-3β and Akt in the liver of mudskippers in the HP group were observably lower than those of mudskippers in the HD group at 24 h, but HIF-1 was significantly higher. On the contrary, at 48 h, the mRNA expression levels of GSK-3β and Akt in the liver of fish in the HP group were significantly higher than those of fish in the HD group, but HIF-1 was significantly lower. The results indicated that mudskippers suffering from hypoxia led to oxygen homeostasis disturbances and apoptosis, but exogenous puerarin or dexamethasone could mitigate the adverse effects. The mRNA of HIF-1 regulation has an important role in enhancing hypoxia tolerance. Full article

Reactive oxygen species (ROS) are an essential component for the maintenance of cellular function. However, if produced in excess, ROS can drive cellular dysfunction and compromise cell viability. Indeed, uncontrolled ROS production plays a pivotal role in the pathogenesis of type 2 diabetes (T2D), contributing to the loss of β-cell function and the impairment in insulin signalling, as well as driving the development of diabetic complications, which can severely compromise quality of life. T2D is characterised by persistent hyperglycaemia, which is a leading contributor to ROS overproduction in this disease state. This enhanced, almost uncontrolled, increase in glucose metabolism upregulates several ROS-producing pathways, including the hexosamine pathway, protein kinase C, NADPH oxidase and the mitochondrial electron transport chain. There is accumulating evidence to suggest that in a bid to preserve redox homeostasis, ROS acts to suppress glucose metabolism by inactivating several enzymes involved in the regulation of glycolytic flux, including glucokinase, glyceraldehyde 3-phosphate dehydrogenase, phosphofructokinase-1 and pyruvate kinase. Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) is a multi-faceted transcription factor, with a central role in ROS signalling and redox homeostasis. Whilst NF-κB mediates the transcriptional regulation of many pro-oxidants, NF-κB activity is also regulated by the oxidative status, with ROS having both inhibitory and stimulatory roles in these signalling pathways. Interestingly, NF-κB is also involved in controlling the delicate balance between glycolytic flux and mitochondrial respiration. This review will summarise the interplay linking hyperglycaemia with ROS formation, emphasising the role of glucose metabolism in the process, and the crosstalk of these pathways with NF-κB. Full article

Background: Obesity is a multifactorial chronic disease resulting from sustained energy imbalance and modulated by environmental and demographic factors, and it is associated with numerous comorbidities. DNA methylation is an epigenetic modification associated with obesity. Modulation of DNA methylation is a viable target for obesity control strategies. The flavanol (-)-epicatechin (EC) exerts beneficial effects in overweight individuals, suggesting that EC may influence gene regulation through signaling pathways and epigenetic mechanisms. We evaluated whether EC modulates obesity-associated DNA methylation changes using complementary in silico, in vitro, and in vivo approaches. Methods. In silico analyses were performed to explore potential EC interactions with the DNA methyltransferases DNMT1, DNMT3A, and DNMT3B. DNMT activity was measured in nuclear extracts of 4T1 cells in the presence of EC. Finally, in a C57BL/6 mouse model of diet- induced obesity, we assessed global DNA methylation and the expression of the DNA methyltransferases, as well as metabolism-related genes; peroxisome proliferator-activated receptor gamma coactivator 1 alpha (Pgc-1α), pyruvate dehydrogenase kinase isozyme 4 (Pdk4), and nuclear factor erythroid 2–related factor 2 (Nrf2) and relative mitochondrial DNA content (mtDNA/nDNA ratio) in visceral adipose tissue (VAT) and skeletal muscle. Results. EC showed stable in silico interactions within catalytic/cofactor-binding regions of DNMTs and inhibited DNMT activity in vitro in a concentration-dependent manner. In vivo, the obesogenic diet reduced global DNA methylation and decreased transcript levels of Dnmt1, Dnmt3a, and Dnmt3b in skeletal muscle and adipose tissue. EC counteracted obesity-associated DNA methylation changes in skeletal muscle, restoring global methylation and Dnmt expression toward control levels, whereas effects in VAT were limited. EC increased mitochondrial DNA content. Discussion. In silico and enzymatic data suggest that EC may bind DNMT active sites and inhibit DNMT activity in a concentration-dependent manner, supporting a role for EC in obesity-related epigenetic remodeling, particularly in skeletal muscle. EC also increased relative mitochondrial DNA content in VAT and skeletal muscle despite no obesogenic diet effect on relative mitochondrial abundance, consistent with favorable mitochondrial modulation. In conclusion, EC is an epigenetic modulator and may have positive effects in obesity related dysfunctional tissues. Full article

Targeting the Warburg effect (aerobic glycolysis) in tumor cells represents a promising metabolic therapeutic strategy in cancer research. This review analyzes the regulatory mechanisms and therapeutic potential of key glycolysis pathway components, including glucose transporters (GLUTs) and glycolytic enzymes such as hexokinase 2 (HK2), phosphofructokinase (PFK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA). We evaluate the molecular mechanisms of various inhibitors and the current clinical development landscape, noting that limitations of monotherapy stem not only from tumor metabolic plasticity but also largely from the unacceptable toxicity of many inhibitors due to the essential role of glycolysis in normal cell metabolism. Furthermore, we explore the molecular basis of synergistic interactions between glycolysis inhibitors and chemotherapy, radiotherapy, immunotherapy, photothermal therapy, and targeted therapy, proposing that rational combination strategies may help overcome resistance and improve therapeutic efficacy. Finally, the review outlines future challenges and directions, emphasizing that the primary obstacle in metabolic treatments is achieving selective inhibition of glycolytic enzymes in cancer cells while sparing normal cells. To address this challenge, the development of high-selectivity agents, cancer-specific nanodelivery systems, precise biomarker identification, and innovative combination regimens based on metabolic-immune regulation is crucial for advancing glycolysis-targeted therapy toward clinical translation. Full article

Metabolic reprogramming is a fundamental hallmark and a key driver of malignant tumors. By reshaping glucose, lipid, and amino acid metabolism, as well as mitochondrial function, it sustains the abnormal proliferation and survival of tumor cells, making it a crucial target for anti-tumor therapy. Curcumin, a natural multi-target compound, exhibits unique advantages in intervening in tumor metabolic reprogramming due to its low toxicity and broad-spectrum regulatory properties. In various tumor models, it can directly modulate the activity of key glycolytic enzymes, such as hexokinase 2, lactate dehydrogenase A, and pyruvate kinase M2, as well as transporters like glucose transporter 1. Furthermore, it inhibits the expression of proteins related to lipid metabolism, including fatty acid synthase and stearoyl-CoA desaturase 1, while also intervening in amino acid metabolic networks, such as glutaminase and branched-chain amino acid transaminase. Additionally, curcumin targets mitochondrial function and reactive oxygen species balance, creating multi-dimensional intervention effects through various pathways, including the induction of ferroptosis by regulating the SLC7A11/GPX4 axis and modulating gut microbiota metabolism. Its mechanism of action involves the synergistic regulation of key signaling pathways, including phosphoinositide 3-kinase/Akt, NF-κB, AMP-activated protein kinase, and hypoxia-inducible factor-1alpha. Furthermore, its specific effect profile demonstrates significant dependency on cell type and tumor model. This article systematically reviews the regulatory effects of curcumin on these critical metabolic processes and pathways in tumor metabolic reprogramming, revealing its molecular mechanisms in disrupting tumor growth and progression by targeting energy and biosynthetic metabolism. These findings provide a significant theoretical foundation and a preclinical research perspective for the development of natural antitumor drugs based on metabolic regulation, as well as for optimizing combination therapy strategies. Full article

The development of males and females of the cephalopod Amphioctopus fangsiao is asynchronous. The male produces sperm after maturity for storage in a spermatophore prior to mating. After mating, the sperm enter the female spermatheca for storage until ovulation occurs, a period that lasts for 8 months. This is a biologically uncommon phenomenon because sperm cells generally fail to maintain their ability to fertilize for a long time after being ejaculated. However, the molecular mechanisms of this phenomenon are still not clear. Sperm cells are stored in the male spermatophore and the female spermatheca, each of which provides a suitable environment. To determine the molecular basis of the sperm storage mechanisms in A. fangsiao, protein profiles from spermathecal fluid and seminal plasma were characterized separately using mass spectrometry-based proteomics. The antioxidant enzymes superoxide dismutase (SOD), glutathione S-transferase (GST), and Thioredoxin (Trx), and the glycolytic enzymes lactate dehydrogenase (LDH), hexokinase (HK), pyruvate dehydrogenase kinase (PDK), and ATP synthase were significantly enriched in the spermathecal fluid. Catalase (CAT), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), triosephosphate isomerase (TIM), phosphoglycerate kinase (PGK), and Chitinase were significantly enriched in the seminal plasma. The antimicrobial proteins transforming growth factor beta regulator 1 (TBRG1) and interleukin enhancer binding factor 2 (ILF2) and the extracellular matrix-related proteins transforming growth factor beta induced protein (TGFBIp) and thrombospondin type-1 domain-containing protein 4 (THSD4) were also significantly expressed in the spermathecal fluid. These proteins may be crucial for successful long-term sperm storage. We measured the activities of four antioxidant enzymes based on the proteomic results, supporting the antioxidant mechanism during the sperm storage process. This study enhances our understanding of the sperm storage ability of A. fangsiao. Full article

Fructophilic lactic acid bacteria (FLAB), Apilactobacillus kunkeei strains AG8 and AG9 were selected in the current study for in-depth analysis. Cultivation on fructose yeast peptone (FYP) medium with varying fructose concentrations (1%, 10%, and 30%) revealed that higher fructose levels promoted acetate production over lactate, confirming a heterofermentative metabolic profile. Ethanol production was negligible, consistent with the absence of alcohol dehydrogenase (ADH) activity. Enzyme assays showed fructokinase activity doubled at 30% fructose, while acetate kinase activity increased and L-lactate dehydrogenase activity decreased. This shift in enzyme ratios from 1:1 at 1% fructose to 10:1 or 15:1 at higher concentrations explains the metabolic preference for acetate. Apb. kunkeei is an obligate FLAB, growing poorly on glucose unless supplemented with external electron acceptors like pyruvate or oxygen. It lacks ADH, but retains acetaldehyde dehydrogenase (ALDH), enabling acetate production and additional ATP generation, enhancing biomass yield. The absence of the adhE gene contributes to NAD+/NADH imbalance and favors acetate production. Gene expression studies targeting fructose transport enzymes showed elevated expression of ABC transporters and carbohydrate metabolism genes in response to fructose. ADH expression remained low across sugar concentrations. Fructokinase gene expression was shown to be strain specific. Neither strain expressed the ABC transporter ATP-binding protein gene on glucose, nor the bacteriocin ABC transporter gene, correlating with the absence of antibacterial activity. These findings underscore the metabolic specialization of Apb. kunkeei, its reliance on fructose, and the role of ABC transporters in optimizing fermentation. The strain-specific gene expression and metabolic flexibility highlight its potential as a probiotic and feed additive in apiculture and biotechnology. Full article