count source_label source_id relationship target_label target_id entity_type solr_id publication_id sentences 8 fructose metabolic process GO:0006000 activates GO:0009058 Phenotype 05287654-cd13-11ee-9aaa-0050569a1f61 10.1016/j.phanu.2014.12.001 Unlike glucose, fructose metabolism in the liver generates AMP and subsequently increased UA synthesis[128]. 4 fructose metabolic process GO:0006000 activates GO:0034418 Phenotype a48e70e6-c46a-11e5-9da3-001a4ae51247 24808490 In addition, unregulated hepatic fructose metabolism may lead to increased urate synthesis. 4 fructose metabolic process GO:0006000 activates GO:0006094 Phenotype 710451e4-3747-11e8-87fd-001a4a160176 26593707 Fructose metabolism induces gluconeogenesis in rat liver (Kinote et al., 2012).|||Betaine suppressed hepatic gluconeogenesis in fructose-fed rats by moderating the activity of AKT-FOXO1, as well as p38 MAPK and mTOR pathway Fructose metabolism induces gluconeogenesis in rat liver (Kinote et al., 2012). 4 UNIPROT:P50053 inhibits fructose metabolic process GO:0006000 Protein 1bc67fee-bc11-11e5-8abe-001a4ae51246 10.1016/j.compbiolchem.2007.06.001 This study shows that the expression of KHK, FBP1 and FBP2 was diminished in gastric cancer cells, suggesting a decelerated fructose metabolism. 4 UNIPROT:P50053 activates fructose metabolic process GO:0006000 Protein 275f8bb0-c6ea-11ee-9aaa-0050569a1f61 10.1016/j.tem.2023.08.007 Fructokinase or ketohexokinase (KHK) mediates the first step in fructose metabolism. 4 CHEBI:16024 activates fructose metabolic process GO:0006000 Chemical c569b76a-1b60-11f0-b759-0050569a791b 10.1016/j.scitotenv.2024.172318 D-mannose synergized with fructose metabolism (pfkfb2,khk) during glucose metabolism, thereby upregulating the expression of downstream D-mannose-1P metabolites in the treatment group and providing energy for body metabolism. 4 UNIPROT:P05062 activates fructose metabolic process GO:0006000 Protein 7c16db92-1bf1-11f0-b759-0050569a791b 10.1016/j.bbcan.2023.189062 Metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and fuels major proliferation pathways [90]. 4 CHEBI:8473 activates fructose metabolic process GO:0006000 Chemical 675bab8a-86ca-11f0-afc2-0050569a791b PMC8168776 Lastly, we sought to demonstrate the SSP-mediated fructose metabolism in patient-derived xenograft (PDX) models. 4 MESH:D000255 activates fructose metabolic process GO:0006000 Phenotype 675bab8a-86ca-11f0-afc2-0050569a791b PMC8168776 Our analysis of the intracellular level of ATP and AMP in MOLM13 cells cultured in glucose-rich or fructose-rich conditions showed that the ratio of ATP to AMP was similar between both conditions (Figure S3E), further supporting that KHK plays a minimal role in AML fructose metabolism. 4 CHEBI:16027 activates fructose metabolic process GO:0006000 Chemical 675bab8a-86ca-11f0-afc2-0050569a791b PMC8168776 Our analysis of the intracellular level of ATP and AMP in MOLM13 cells cultured in glucose-rich or fructose-rich conditions showed that the ratio of ATP to AMP was similar between both conditions (Figure S3E), further supporting that KHK plays a minimal role in AML fructose metabolism. 4 UNIPROT:P09467 inhibits fructose metabolic process GO:0006000 Protein 1bc67fee-bc11-11e5-8abe-001a4ae51246 10.1016/j.compbiolchem.2007.06.001 This study shows that the expression of KHK, FBP1 and FBP2 was diminished in gastric cancer cells, suggesting a decelerated fructose metabolism. 4 PF:PF01081 activates fructose metabolic process GO:0006000 ProteinFamily 7c16db92-1bf1-11f0-b759-0050569a791b 10.1016/j.bbcan.2023.189062 Metastatic cells in the liver upregulate the enzyme aldolase B (ALDOB), which enhances fructose metabolism and fuels major proliferation pathways [90]. 4 UNIPROT:O00757 inhibits fructose metabolic process GO:0006000 Protein 1bc67fee-bc11-11e5-8abe-001a4ae51246 10.1016/j.compbiolchem.2007.06.001 This study shows that the expression of KHK, FBP1 and FBP2 was diminished in gastric cancer cells, suggesting a decelerated fructose metabolism. 3 UNIPROT:P22732 activates fructose metabolic process GO:0006000 Protein 30bdb406-7c4f-11ee-add2-0050569a791b 10.1007/s12094-022-03015-2 However, the role of GLUT5-mediated fructose metabolism in lung cancer metastasis and its underlying molecular mechanisms are poorly addressed.|||Indeed, we accordingly explored the downstream signaling of enhanced fructose metabolism mediated by GLUT5.|||5Proposed model illustrates that GLUT5-mediated fructose metabolism promotes lung cancer cell migration Discussion discussion Accumulated evidences demonstrate that fructose transporter GLUT5 is significantly upregulated in various cancers, including clear renal cell carcinoma [32], glioma [19], lung adenocarcinoma [20], breast cancer [14], colorectal cancer [33], and so on. 2 fructose metabolic process GO:0006000 activates GO:0006094 Phenotype 5602526e-bc2a-11e5-8abe-001a4ae51246 10.1016/j.bbagen.2004.10.001 The current results complement these findings and suggest that increased fructose metabolism is contributing to gluconeogenesis in the liver of CR mice. 2 fructose metabolic process GO:0006000 activates GO:0008610 Phenotype 5587a96c-e9f5-11ef-b449-0050569a791b 10.1016/j.fbio.2024.105720 Fructose metabolism indirectly leads to hepatic insulin resistance through clear pathways, including the promotion of de novo lipogenesis and inducing liver inflammation. 2 fructose metabolic process GO:0006000 activates GO:0009414 Phenotype cb0fb31c-c72f-11ee-b346-0050569a791b 10.1016/j.jprot.2023.105010 Proteomic analyses suggested that Z-3-HAC might enhance the drought tolerance of LJCY by fructose metabolism while enhancing the drought tolerance of ZC108 by promoting glucan biosynthesis and galactose metabolism. 2 fructose metabolic process GO:0006000 activates GO:0009058 Phenotype bade522a-5c13-11e7-8c5f-001a4ae51246 PMC5430158 Fructose metabolism leads to increased intracellular uric acid (UA) synthesis[15]. 2 fructose metabolic process GO:0006000 activates GO:0009058 Phenotype 8a548136-8d84-11e7-a20e-001a4ae51247 PMC5512153 Intracellular fructose metabolism leads to increased UA synthesis[112],[113]. 2 fructose metabolic process GO:0006000 activates GO:0008283 Phenotype 6462ed38-1b1f-11f0-b759-0050569a791b 10.1016/j.apsb.2024.04.024 ALDOB is also a key enzyme in fructose metabolism, which converts fructose-1-phosphate into glyceraldehyde and dihydroxyacetone phosphate and is upregulated after colorectal cancer cells colonize in the liver and accelerate cancer cell proliferation in livers. 2 fructose metabolic process GO:0006000 inhibits GO:0008152 Phenotype ffb172a8-c8de-11ee-b346-0050569a791b PMC10196606 Unlike glucose, which is a source for immediate energy needs, fructose metabolism results in an orchestrated response to encourage food and water intake, reduce resting metabolism, stimulate fat and glycogen accumulation, and induce insulin resistance as a means to reduce metabolism and preserve glucose supply for the brain. 2 fructose metabolic process GO:0006000 activates GO:0006950 Phenotype 4bb8a7e8-c835-11ee-b346-0050569a791b 10.1016/j.ijfoodmicro.2023.110165 Lactose and fructose metabolism are known to activate the general stress response regulator SigB and upregulate stress response geneclpC, respectively (Liu et al., 2017;Tapia et al., 2020), while glycerol metabolism is impaired in the absence ofsigB(Abram et al., 2008). 2 UNIPROT:P50053 activates fructose metabolic process GO:0006000 Protein 1a0abd20-f58b-11eb-8c07-001a4a160175 30778703 In particular, metastatic cells in the liver up-regulate the enzyme aldolase B (ALDOB) and ketohexokinase (KHK), which enhances fructose metabolism and provides fuel for major pathways of central carbon metabolism, nucleotide synthesis, and lipid synthesis during tumor cell proliferation. 2 MESH:D013395 activates fructose metabolic process GO:0006000 Phenotype 1722e6f2-0550-11f0-9c9e-0050569a1f61 10.1016/j.fbio.2024.104368 High sucrose diet increased the fructose metabolism and glycolysis (KHK and PKLR), resulting in production of pyruvate, a crucial precursor for de novo lipogenesis (Fig. 2a and b). 2 UNIPROT:P05062 activates fructose metabolic process GO:0006000 Protein 6462ed38-1b1f-11f0-b759-0050569a791b 10.1016/j.apsb.2024.04.024 Colorectal cancer cells undergo metabolic reprogramming after colonization in the liver, and the upregulation of aldolase B (ALDOB) enhances fructose metabolism and provides carbon source for tumor cell proliferation10. 2 UNIPROT:P05062 activates fructose metabolic process GO:0006000 Protein 7efa50a0-ae94-11ec-b4ed-0050569a1f61 PMCPMC8110832 However, another study found that ALDOB is significantly up-regulated by GATA6 in metastatic liver cancer cell HCT116 to accelerate fructose metabolism, which is beneficial to tumor cell proliferation and metastasis (Li et al., 2017). 2 MESH:D009362 activates fructose metabolic process GO:0006000 Phenotype 952c6ed6-4562-11f0-afc2-0050569a791b 10.1016/j.humimm.2022.03.007 Goncalves et al. studied primary colon carcinoma and liver metastasis samples and found that the upregulation of aldolase B expression in liver metastases enhanced fructose metabolism compared with primary tumors, while GLUT5 levels were not significantly different[114]. 2 GO:0008152 activates fructose metabolic process GO:0006000 Phenotype 76facf5c-1b14-11f0-b759-0050569a791b 10.1016/j.carres.2024.109169 Nonetheless, it is described that the associated neighbouring pathways (Pentose Phosphate Pathway, Fatty Acid Synthesis, Hexosamine biosynthesis, glutaminolysis, fructose metabolism, mannose metabolism, galactose metabolism, etc) can be modulated by the central biochemical metabolism. 2 UNIPROT:Q92908 activates fructose metabolic process GO:0006000 Protein 7efa50a0-ae94-11ec-b4ed-0050569a1f61 PMCPMC8110832 However, another study found that ALDOB is significantly up-regulated by GATA6 in metastatic liver cancer cell HCT116 to accelerate fructose metabolism, which is beneficial to tumor cell proliferation and metastasis (Li et al., 2017). 2 PF:PF01081 activates fructose metabolic process GO:0006000 ProteinFamily 6462ed38-1b1f-11f0-b759-0050569a791b 10.1016/j.apsb.2024.04.024 Colorectal cancer cells undergo metabolic reprogramming after colonization in the liver, and the upregulation of aldolase B (ALDOB) enhances fructose metabolism and provides carbon source for tumor cell proliferation10. 2 PF:PF01081 activates fructose metabolic process GO:0006000 ProteinFamily 952c6ed6-4562-11f0-afc2-0050569a791b 10.1016/j.humimm.2022.03.007 Goncalves et al. studied primary colon carcinoma and liver metastasis samples and found that the upregulation of aldolase B expression in liver metastases enhanced fructose metabolism compared with primary tumors, while GLUT5 levels were not significantly different[114]. 2 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical 6d515bd4-1c4e-11f0-b759-0050569a791b 10.1016/j.ctarc.2025.100876 Uric acid is also a by-product of fructose metabolism, which can result in oxidative stress and inflammation [7]. 2 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical ccc3fadc-3749-11e8-8636-001a4a160175 26133655 However, uric acid also significantly increases TAG accumulation, even in cells lacking fructokinase and aldolase B enzyme expression, suggesting that uric acid might function independently of direct fructose metabolism[29]. 2 CHEBI:16908 activates fructose metabolic process GO:0006000 Chemical 675bab8a-86ca-11f0-afc2-0050569a791b PMC8168776 We have found that fructose metabolism through the SSP in AML cells is mediated by redox cofactors, NAD+and NADH, whose ratio is significantly higher in fructose-rich conditions than glucose-rich conditions. 2 FPLX:HIF1 activates fructose metabolic process GO:0006000 ProteinFamily 1f5d063a-8e17-11e7-97d2-001a4ae51247 26896647 Thus, activation of fructose metabolism by HIF1α is emerging as a central component of hypoxia-driven metabolic programs dedicated to enhance macromolecular biosynthetic capacity for hypertrophic growth of the myocardium.|||However, recent evidence suggests a molecular mechanism by which fructose metabolism can be activated by HIF1α to support cardiac hypertrophic growth[10]. 2 UNIPROT:P05062 activates fructose metabolic process GO:0006000 Protein 1cbe26d6-95e3-11e9-bffb-001a4a160175 PMC5990465 ALDOB Enhances Fructose Metabolism The products of ALDOB-mediated reactions could contribute to glucose, glycogen, lactate, and lipid synthesis, all essential for sustaining highly proliferative cells.|||Metabolomics and13C-labeled fructose tracing studies indicate that ALDOB promotes fructose metabolism to fuel glycolysis, gluconeogenesis, and the pentose phosphate pathway. 2 CHEBI:32398 activates fructose metabolic process GO:0006000 Chemical f80df234-1a53-11f0-aa93-0050569a1f61 10.1016/j.ymgmr.2024.101159 Discussion D-glyceric acid (Fig. 1) is an intermediate of serine and fructose metabolism [6,7].|||D-glyceric acid (Fig. 1) is an intermediate of serine and fructose metabolism [6,7]. 2 PF:PF01081 inhibits fructose metabolic process GO:0006000 ProteinFamily dc984dcb-f588-11eb-8b45-001a4a160175 30327278 " Institute for Maternal and Child Health IRCCS “Burlo Garofolo” Via dell'Istria 65/1, IRCCS Burlo Garofolo Trieste 34100 Italy Hereditary fructose intolerance is an autosomal recessive disorder of fructose metabolism caused by catalytic deficiency of aldolase B enzyme [1].|||Da Lozzo, PriscaMagnolato, AndreaDel Rizzo, IreneSirchia, FabioBruno, IreneBarbi, Egidio Hereditary fructose intolerance is an autosomal recessive disorder of fructose metabolism caused by catalytic deficiency of aldolase B enzyme [1]." 1 fructose metabolic process GO:0006000 inhibits CHEBI:27226 Chemical 5c93c848-c9e0-11ee-9aaa-0050569a1f61 10.1016/j.ijbiomac.2022.09.231 Interestingly, Fuc treatment also attenuated LPS-induced fructose metabolism in brain tissue by increasing fructose residues and reducing uric acid (UA) content (Fig. 10E and F,P< 0.05). 1 fructose metabolic process GO:0006000 activates GO:0008610 Phenotype 4ab5f888-c726-11ee-b346-0050569a791b 10.1016/j.numecd.2023.07.009 In fact, fructose metabolism stimulates free radical production, lipogenesis and the level of serum lipopolysaccharides [38]. 1 fructose metabolic process GO:0006000 activates GO:0008610 Phenotype 3cf09c34-c830-11ee-b22c-0050569a1f61 10.1016/j.ejphar.2023.175728 Fructose metabolism by the liver increases lipogenesis by blocking phosphofructokinase, increasing oxidative damage, lipid peroxidation and the likelihood of nonalcoholic fatty liver disease (Basaranoglu et al., 2015), (Alwahsh and Gebhardt, 2017). 1 fructose metabolic process GO:0006000 activates GO:0008610 Phenotype 20196856-c7cd-11ee-ae05-0050569a1f61 PMC10752375 This may be secondary to increased lipogenesis, triggered by fructose metabolism and upregulation of KHK-C, which propagates ER stress-induced liver injury. 1 fructose metabolic process GO:0006000 activates GO:0008610 Phenotype fd62dab0-328d-11e9-87c2-001a4a160175 PMC6463203 Studies of adipocytes in culture show that fructose, but not glucose, has a trophic effect on the cells, stimulating the expansion of adipocyte precursors.48Not surprisingly, fructose metabolism by adipocytes also promotes lipogenesis, leading to storage of some of the fatty acids and the release of some as FFA.49Studies have shown that fructose, but not glucose, consumption causes insulin resistance.32,42This acts as an ongoing stimulus to lipolysis in fructose-exposed adipose tissue. 1 fructose metabolic process GO:0006000 activates GO:0008610 Phenotype 6787014e-ae93-11ec-8b2e-0050569a1f61 PMC8626588 Fructose metabolism promotes de novo lipid biosynthesis in the liver and is hypothesized to be a key contributor to NAFLD progression, including NASH (26), and our data support this idea. 1 fructose metabolic process GO:0006000 activates GO:0008610 Phenotype 0811fa1c-c474-11e5-8491-001a4ae51247 PMC4443321 "Whereas glucose is the main circulating sugar in the blood, the majority of fructose is extracted from the bloodstream into the liver, where unregulated fructose metabolism can lead to increased lipogenesis (3)." 1 fructose metabolic process GO:0006000 inhibits GO:0008610 Phenotype ce818b04-80ff-11ee-9572-0050569a1f61 10.1007/s11739-022-03139-x Some of the new clinical phase III trials include inhibitors of ketohexokinase that block the final step of fructose metabolism inhibiting lipogenesis [67]. 1 fructose metabolic process GO:0006000 activates GO:0032602 Phenotype b4f29baf-f587-11eb-93da-001a4a160176 30240793 Fructose metabolism through fructokinase enhances uric acid synthesis, oxidative stress and chemokine production thus leading to tubular injury. 1 fructose metabolic process GO:0006000 activates GO:0016477 Phenotype 30bdb406-7c4f-11ee-add2-0050569a791b 10.1007/s12094-022-03015-2 5Proposed model illustrates that GLUT5-mediated fructose metabolism promotes lung cancer cell migration Discussion discussion Accumulated evidences demonstrate that fructose transporter GLUT5 is significantly upregulated in various cancers, including clear renal cell carcinoma [32], glioma [19], lung adenocarcinoma [20], breast cancer [14], colorectal cancer [33], and so on. 1 fructose metabolic process GO:0006000 activates GO:0009051 Phenotype 30bdb406-7c4f-11ee-add2-0050569a791b 10.1007/s12094-022-03015-2 Activated fructose metabolism induces thiamine-dependent trans-ketolase flux and non-oxidative pentose phosphate pathway to synthesize nucleic acids and produce uric acid in pancreatic cancer [17]. 1 fructose metabolic process GO:0006000 activates GO:0006351 Phenotype 618a8332-c8c3-11ee-ae05-0050569a1f61 10.1016/j.jnutbio.2022.109224 Aside from providing substrate for lipogenesis, fructose metabolism activates lipogenic transcription factors that govern the expression of lipogenic enzymes. 1 fructose metabolic process GO:0006000 activates GO:0009058 Phenotype b4f29baf-f587-11eb-93da-001a4a160176 30240793 Fructose metabolism through fructokinase enhances uric acid synthesis, oxidative stress and chemokine production thus leading to tubular injury. 1 fructose metabolic process GO:0006000 activates GO:0009058 Phenotype b6a71eac-cf90-11e8-9c11-001a4a160175 PMC6222386 Fructose metabolism promotes and enhances synthesis of lipids in the liver by providing substrates for lipogenesis and activating SREBP-1c [26,27,28,30]. 1 fructose metabolic process GO:0006000 activates GO:0009058 Phenotype a52ac70d-f58a-11eb-8bec-001a4a160175 30768981 As fructose metabolism promotes triglycerides synthesis and consequently TG-enrichment of lipoproteins (e.g. 1 fructose metabolic process GO:0006000 activates MESH:D009362 Phenotype 6cfc1184-ae8a-11ee-a19b-0050569a791b 10.1038/s43018-020-0086-7 Aldob-mediated fructose metabolism drives metabolic reprogramming and promotes colorectal cancer (CRC) metastasis to the liver26. 1 fructose metabolic process GO:0006000 activates GO:0008152 Phenotype 822d2b59-f588-11eb-8b1e-001a4a160175 30803508 UA overproduction in Western population is caused by increased fructose consumption, as fructose metabolism induces increased purine metabolism[52]. 1 fructose metabolic process GO:0006000 activates GO:0008152 Phenotype ffb172a8-c8de-11ee-b346-0050569a791b PMC10196606 However, the chronic and persistent decrease in cerebral metabolism driven by recurrent fructose metabolism leads to progressive brain atrophy and neuron loss with all of the features of AD. 1 fructose metabolic process GO:0006000 inhibits GO:0008152 Phenotype e978a862-c6fe-11ee-b346-0050569a791b 10.1016/j.scitotenv.2023.165614 Mannose and fructose metabolism was downregulated in the washed group and normalised in the control, suggesting e-beam treated pollen is altered and affecting the metabolism of the colonies. 1 fructose metabolic process GO:0006000 activates MESH:D002241 Phenotype 750e1834-3a9d-11e8-9fbf-001a4a160176 23022226 Dietary carbohydrate raises hepatic phosphorylated intermediates: roles for G6PC, GCKR and ChREBP in phosphate homeostasis A carbohydrate-containing meal raises the hepatic concentrations of phosphorylated intermediates of glucose and fructose metabolism with the magnitude of the increase being dependent on carbohydrate load and composition[55]. 1 fructose metabolic process GO:0006000 activates GO:0006954 Phenotype 5312dd10-ea31-11ee-b346-0050569a791b 10.1016/j.tice.2022.101894 Also, fructose metabolism leads to hepatic insulin resistance by promoting de novo lipogenesis, impairing fatty acid oxidation, inducing endoplasmic reticulum stress, and triggering hepatic inflammation (Softic et al., 2020). 1 fructose metabolic process GO:0006000 activates GO:0006954 Phenotype dca15cb8-ae93-11ec-89b1-0050569a791b PMC8346650 These published results, combined with the data produced in this study, suggest that fructose metabolism defects in ALS may contribute to the AGE influence on metabolic dysfunction, oxidative stress and inflammation and may be enhanced with aging.Interestingly, we found that glycogen metabolism was negatively correlated with age in the ALS fibroblast cohort, which was not observed in control fibroblasts (Fig. 4). 1 fructose metabolic process GO:0006000 activates GO:0006954 Phenotype 3675f648-ea0d-11ee-b346-0050569a791b 10.1016/j.joclim.2022.100143 Fructose metabolism by fructokinase mediates inflammation and tubular injury[10]. 1 fructose metabolic process GO:0006000 activates GO:0006954 Phenotype b6aa5ff8-7b80-11ee-add2-0050569a791b 10.1007/s12011-023-03685-1 Fructose metabolism can induce oxidative stress and, in turn, promote an inflammatory response that leads to the development of insulin resistance [23]. 1 fructose metabolic process GO:0006000 activates GO:0006954 Phenotype c71438c8-352c-11e8-bf76-001a4a160175 27060421 Ultimately, AMP deaminase activation ensues and results in uric acid production,42-44thus stimulating further fructokinase function and fructose-induced lipogenesis in hepatocytes.45This metabolic disturbance has been also shown in diabetic patients and in other human studies.41,46-48Moreover, fructose metabolism has been shown to increase expression of protein tyrosine phosphatase 1B (PTP1B), phosphorylation of c-Jun N-terminal kinase (JNK), and downstream targets of JNK63-known mediators of inflammation in liver cells (PTP1B, phos-c-JNK, JNK63 targets49). 1 fructose metabolic process GO:0006000 activates GO:0019395 Phenotype 618a8332-c8c3-11ee-ae05-0050569a1f61 10.1016/j.jnutbio.2022.109224 In agreement with this, we published that abrogating fructose metabolism in the livers of mice on a most commonly utilized obesogenic HFD (Research diets, D12492, 60% calories from fat), which also contains 6.7% of sugar, leads to increased mitochondrial fatty acid oxidation and improved metabolic health[23]. 1 fructose metabolic process GO:0006000 activates GO:0019395 Phenotype 5312dd10-ea31-11ee-b346-0050569a791b 10.1016/j.tice.2022.101894 Also, fructose metabolism leads to hepatic insulin resistance by promoting de novo lipogenesis, impairing fatty acid oxidation, inducing endoplasmic reticulum stress, and triggering hepatic inflammation (Softic et al., 2020). 1 fructose metabolic process GO:0006000 inhibits GO:0006099 Phenotype 02227928-ae93-11ec-b4ed-0050569a1f61 PMCPMC8243983 While fructose metabolism inhibits aconitase, and therefore suppresses TCA cycle, glutamine metabolism supplies α-ketoglutarate that can bypass this step allowing oxidative phosphorylation to occur (70,71). 1 fructose metabolic process GO:0006000 activates MESH:D002470 Phenotype c5b17cd0-ea1f-11ee-b346-0050569a791b 10.1053/j.gastro.2022.06.022 These results support that fructose metabolism promotes hypoxemic cell survival in the intestine. 1 fructose metabolic process GO:0006000 inhibits GO:0046960 Phenotype 51727bb4-374f-11e8-a51f-001a4a160176 28429085 The latter study demonstrated that when glucose is depleted in bone marrow, AML cells switch to fructose utilization and pharmacological inhibition of fructose metabolism reduces the leukemic phenotype and increases sensitization to cytotoxic agents, suggesting a potential therapeutic target. 1 fructose metabolic process GO:0006000 activates MESH:D005632 Phenotype 5c93c848-c9e0-11ee-9aaa-0050569a1f61 10.1016/j.ijbiomac.2022.09.231 Interestingly, Fuc treatment also attenuated LPS-induced fructose metabolism in brain tissue by increasing fructose residues and reducing uric acid (UA) content (Fig. 10E and F,P< 0.05). 1 fructose metabolic process GO:0006000 inhibits MESH:D005632 Phenotype 5c93c848-c9e0-11ee-9aaa-0050569a1f61 10.1016/j.ijbiomac.2022.09.231 Interestingly, Fuc treatment also attenuated LPS-induced fructose metabolism in brain tissue by increasing fructose residues and reducing uric acid (UA) content (Fig. 10E and F,P< 0.05). 1 fructose metabolic process GO:0006000 activates GO:0006096 Phenotype 30bdb406-7c4f-11ee-add2-0050569a791b 10.1007/s12094-022-03015-2 3Enhanced fructose metabolism activates glycolysis to induce AKT phosphorylation.ALactate levels were detected when cells with or without ectopic GLUT5 were cultured under the condition of 6 mM fructose.BAfterSLC2A5was knocked out in lung cancer cells, lactate production was examined at different time points (0, 0.5, 1, 2, 4, 8, 12, 24 h), individually.CLactate production at various time points was assayed after the cells were treated by glycolysis inhibitor 2-DG.DA549 cells with overexpressed GLUT5 were cultured under 6 mM fructose and treated with 2-DG in low (5 mM) or high (10 mM) concentration. 1 fructose metabolic process GO:0006000 activates GO:0006096 Phenotype cc08481e-ea67-11ee-9133-0050569a1f61 10.1016/j.jff.2022.105216 However, excessive activation of HIF-1α will cause changes in cardiomyocyte metabolism, such as increased glycolysis and lipid accumulation caused by activation of the HIF-1α/PPARγ axis and upregulation of fructose metabolism in cardiomyocytes induced by HIF-1α-SF3B1-KHK-C axis, which are reflected in models of pathological cardiac hypertrophy (Krishnan et al., 2009; Mirtschink et al., 2015). 1 fructose metabolic process GO:0006000 activates GO:0006096 Phenotype 4bb606a4-ae93-11ec-b4ed-0050569a1f61 PMCPMC8467942 Fructose metabolism increases aerobic glycolysis and down-regulates mitochondrial respiration [25]. 1 GO:0042592 activates fructose metabolic process GO:0006000 Phenotype 750e1834-3a9d-11e8-9fbf-001a4a160176 23022226 Dietary carbohydrate raises hepatic phosphorylated intermediates: roles for G6PC, GCKR and ChREBP in phosphate homeostasis A carbohydrate-containing meal raises the hepatic concentrations of phosphorylated intermediates of glucose and fructose metabolism with the magnitude of the increase being dependent on carbohydrate load and composition[55]. 1 UNIPROT:Q16236 activates fructose metabolic process GO:0006000 Protein bafdf658-3c6f-11f0-afc2-0050569a791b 10.1016/j.freeradbiomed.2022.06.226 "In the context of Nrf2-mediated inducible protection against fructose-stimulated NASH, it should also be noted that Nrf2 can increase fructose metabolism and gluconeogenesis by inducing fructokinase and HNF4A, along with SORD and TKFC [193] and this may influence the ability of fructose to damage hepatocytes." 1 UNIPROT:P50053 activates fructose metabolic process GO:0006000 Protein 618a8332-c8c3-11ee-ae05-0050569a1f61 10.1016/j.jnutbio.2022.109224 We[23]and others[28]have shown that these effects are dependent on KHK mediated fructose metabolism[111]. 1 UNIPROT:P50053 activates fructose metabolic process GO:0006000 Protein b8e5129a-ae8f-11e8-ad55-001a4a160175 PMC6177502 Patel Cet al. showed that fructose absorption via GLUT5 and KHK-mediated fructose metabolism are required for the regulation of intestinal fructolytic and gluconeogenic enzymes (68). 1 UNIPROT:P50053 activates fructose metabolic process GO:0006000 Protein 422010b8-c465-11e5-9da3-001a4ae51247 24177030 Before testing our hypothesis, we wanted to demonstrate that CaBP9k is found in cells where KHK-mediated fructose metabolism occurs. 1 UNIPROT:P50053 activates fructose metabolic process GO:0006000 Protein be439e0c-352e-11e9-913f-001a4a160175 PMC6095711 Moreover, keratinocytes expressGlut5, SGLT1(Fig. S1d–e), and ketohexokinase which should allow for fructose metabolism to occur. 1 UNIPROT:P50053 activates fructose metabolic process GO:0006000 Protein b1ad3764-f58c-11eb-8c89-001a4a160175 30031605 In addition, the patients with both KHK and GLUT5 higher expression had the worst prognosis, and both KHK and GLUT5 higher expression could be as a predictor of survival in multivariate analysis, which suggested that both KHK and GLUT5 were necessary for fructose metabolism in glioma. 1 MESH:D013395 activates fructose metabolic process GO:0006000 Phenotype 45c62b28-95e3-11e9-922b-001a4a160176 10.1016/j.cmet.2018.02.013 Supporting this, when doses are scaled to body surface area (more appropriate for comparing mice and human oral dosing), the saturation of intestinal fructose metabolism would occur at only ∼5 g sugar intake (e.g., one-fourth of a banana). 1 CHEBI:17234 activates fructose metabolic process GO:0006000 Chemical 0995139e-bc20-11e5-9b9d-001a4ae51247 PMC4113761 Modulation of Fructose Metabolism by Glucose Postprandial plasma fructose concentrations were identical when the test meal included fructose alone and both fructose and glucose. 1 CHEBI:17234 activates fructose metabolic process GO:0006000 Chemical 3bb53ca8-c922-11e7-8d2b-001a4a160176 PMC5886915 High glucose concentrations in renal tubules may lead to altered fructose metabolism in S3 proximal tubular cells and eventually to local tubular injury from increased oxidative stress, uric acid generation and release of inflammatory chemokines [11]. 1 CHEBI:17234 activates fructose metabolic process GO:0006000 Chemical 736f6e60-5c2c-11e7-9833-001a4ae51246 PMC5331612 Fructose Metabolism As with genes related to fructose metabolism, glucose enhances fructose absorption in the intestine. 1 CHEBI:17234 activates fructose metabolic process GO:0006000 Chemical 26433bbc-bc50-11e5-8d2d-001a4ae51247 PMC3781481 While some visceral fat and weight gain occur in glucose-fed mice lacking KHK, the development of fatty liver and hyperinsulinemia are almost entirely dependent on glucose-induced fructose metabolism (91). 1 MESH:D005990 inhibits fructose metabolic process GO:0006000 Phenotype 730f863e-c480-11e5-9da3-001a4ae51247 PMC2981212 "To directly examine the role of GlpR in this phenomenon and determine whether glycerol represses fructose metabolism, theglpRdeletion was introduced into a previously described glycerol kinase (glpK) mutant strain, KS4 (38), for phenotypic analysis." 1 UNIPROT:P0ACL0 inhibits fructose metabolic process GO:0006000 Protein 23382dd0-351d-11e9-ab56-001a4a160175 PMC6088158 These data support our model that (i) GlpR is a repressor of fructose metabolism when fructose is not present in the environment and (ii) the two C/A-rich motifs of thefbapromoter region are required for GlpR-dependent regulation. 1 UNIPROT:F4I0K2 inhibits fructose metabolic process GO:0006000 Protein 0284889c-8dc9-11e7-97d2-001a4ae51247 PMC5244295 RESULTS AND DISCUSSION Effect offruR,pfkB1, andptsFdeletions and carbon sources on aerobic growth and oxygen-deprived glucose consumption.We disrupted the fructose metabolism genesfruR,pfkB1, andptsF, thus creating the respective deletion mutants ofC. 1 MESH:D009369 activates fructose metabolic process GO:0006000 Phenotype fc79fc9e-c6b9-11ee-9aaa-0050569a1f61 10.1016/j.cmet.2023.09.011 Introduction Increasing evidence indicates an association between fructose consumption and cancer incidence.1High fructose consumption enhances liver and colorectal tumorigenesis in mice.2,3,4,5Consumption of a high-fructose diet triggers hepatocellular carcinoma (HCC) development in theMUP-uPAmouse model.4High-fructose corn syrup-treated adenomatous polyposis coli (APC)-mutant mice show a substantial increase in tumor size and tumor grade independent of obesity or metabolic syndrome.3Feeding mice high-fructose corn syrup promotes intestinal cell survival and improves nutrient absorption and tumor growth.5Additionally, aldolase B-mediated fructose metabolism drives tumor metastasis in mouse models of colorectal cancer (CRC).6These observations suggest that fructose consumption increases the risk of HCC and CRC. 1 FPLX:HIF1 activates fructose metabolic process GO:0006000 ProteinFamily e5521198-ae95-11ec-89b1-0050569a791b PMCPMC8222303 Recently HIF1-dependent changes in splicing factor expression were found to drive the maladaptive fructose metabolism observed in heart disease6. 1 MESH:D010100 inhibits fructose metabolic process GO:0006000 Phenotype 0284889c-8dc9-11e7-97d2-001a4ae51247 PMC5244295 RESULTS AND DISCUSSION Effect offruR,pfkB1, andptsFdeletions and carbon sources on aerobic growth and oxygen-deprived glucose consumption.We disrupted the fructose metabolism genesfruR,pfkB1, andptsF, thus creating the respective deletion mutants ofC. 1 UNIPROT:P09601 activates fructose metabolic process GO:0006000 Protein 5777364c-bc4c-11e5-ac4e-001a4ae51246 PMC4670680 Effect of HO-1 Induction on XO and Uric Acids Levels in MSC-Derived Adipocytes Fructose metabolism invokes the consumption of ATP and thereby increases intracellular activity of XO and its product, uric acid. 1 CHEBI:78737 activates fructose metabolic process GO:0006000 Chemical 944780d4-8a72-11ee-add2-0050569a791b 10.1007/s00203-022-03053-y Fructose-1-phosphate is the first product of fructose metabolism. 1 CHEBI:78737 activates fructose metabolic process GO:0006000 Chemical 173705f8-bc38-11e5-9b9d-001a4ae51247 PMC3494720 While the stimulation of AMPD activity has been attributed to the phosphate and GTP depletion that occurs with fructose incubation, we also found that fructose-1-phosphate, a product of fructokinase-mediated fructose metabolism, also stimulated AMPD activity (Fig. 5C, right). 1 FPLX:CCT:complex activates fructose metabolic process GO:0006000 ProteinFamily 802b138c-351d-11e8-87fd-001a4a160176 28591561 Fructose metabolism and uptake related genes present inCupriavidusspecies, as ABC transporters, phosphotransferase systems or 6-phosphofructokinase, were indeed shown to be upregulated by such chaperonin in bacteria (Dills et al., 1980; Tomas et al., 2004; von Rozycki et al., 2005). 1 UNIPROT:P22732 activates fructose metabolic process GO:0006000 Protein b1ad3764-f58c-11eb-8c89-001a4a160175 30031605 In addition, the patients with both KHK and GLUT5 higher expression had the worst prognosis, and both KHK and GLUT5 higher expression could be as a predictor of survival in multivariate analysis, which suggested that both KHK and GLUT5 were necessary for fructose metabolism in glioma. 1 UNIPROT:P05062 activates fructose metabolic process GO:0006000 Protein b6d89f5e-adc6-11e8-92f0-001a4a160176 30154190 Similarly, another study found that exposure to the metabolic environment of the liver prompted colon cancer cells to upregulate aldolase B (ALDOB), which enhanced fructose metabolism and allowed metastatic outgrowth (Bu et al., 2018). 1 UNIPROT:P05062 activates fructose metabolic process GO:0006000 Protein f154b6ef-abd7-11eb-8312-001a4a160175 PMCPMC8036928 Precisely, another isoform of this enzyme, ALDOB, is found to enhance fructose metabolism in colorectal metastatic cancer cells as a response to elevated fructose concentration that is present in the liver [4]. 1 UNIPROT:P05062 activates fructose metabolic process GO:0006000 Protein c2cad667-3876-11eb-88d0-001a4a160176 PMC7744066 In humans, gene dysfunction or deficiency of Aldob causes hereditary fructose intolerance (HFI), a recessively inherited disorder of fructose metabolism [11]. 1 UNIPROT:P05062 activates fructose metabolic process GO:0006000 Protein 6cfc1184-ae8a-11ee-a19b-0050569a791b 10.1038/s43018-020-0086-7 Aldob-mediated fructose metabolism drives metabolic reprogramming and promotes colorectal cancer (CRC) metastasis to the liver26. 1 UNIPROT:Q9UK99 activates fructose metabolic process GO:0006000 Protein eb28c958-c46e-11e5-9cc6-001a4ae51246 PMC3957730 "Furthermore, significant upregulation of thepfkBtranscript (glpR-pfkBoperon and monocistronic transcript) as well as thefbatranscript was observed in the presence of fructose, which was reflected at the enzyme level by 3- and 8-fold-higher 1-PFK and FBA activities, respectively, supporting the function of both enzymes in fructose metabolism (123)." 1 CHEBI:26020 activates fructose metabolic process GO:0006000 Chemical 750e1834-3a9d-11e8-9fbf-001a4a160176 23022226 Dietary carbohydrate raises hepatic phosphorylated intermediates: roles for G6PC, GCKR and ChREBP in phosphate homeostasis A carbohydrate-containing meal raises the hepatic concentrations of phosphorylated intermediates of glucose and fructose metabolism with the magnitude of the increase being dependent on carbohydrate load and composition[55]. 1 UNIPROT:Q92908 activates fructose metabolic process GO:0006000 Protein 6cfc1184-ae8a-11ee-a19b-0050569a791b 10.1038/s43018-020-0086-7 A recent study suggests that GATA6 regulates the expression of Aldob to promote fructose metabolism and liver metastasis of CRC26. 1 MESH:D007288 activates fructose metabolic process GO:0006000 Phenotype 3a784a99-f588-11eb-93fd-001a4a160176 30852460 In addition, based on our previous study[25], DM9128 has the high ability to degrade inosine, which is an intermediate product of fructose metabolism that causes the elevation of serum uric acid. 1 PF:PF01081 activates fructose metabolic process GO:0006000 ProteinFamily b6d89f5e-adc6-11e8-92f0-001a4a160176 30154190 Similarly, another study found that exposure to the metabolic environment of the liver prompted colon cancer cells to upregulate aldolase B (ALDOB), which enhanced fructose metabolism and allowed metastatic outgrowth (Bu et al., 2018). 1 UNIPROT:P40713 activates fructose metabolic process GO:0006000 Protein 376de9f0-bbfb-11e5-8abe-001a4ae51246 10.1016/j.jplph.2010.10.002 While the main role of fructokinase is to mediate fructose metabolism intracellularly, it has been proposed that this enzyme could have a signaling role similar to hexokinase (Pego and Smeekens, 2000). 1 UNIPROT:P40713 activates fructose metabolic process GO:0006000 Protein 173705f8-bc38-11e5-9b9d-001a4ae51247 PMC3494720 While the stimulation of AMPD activity has been attributed to the phosphate and GTP depletion that occurs with fructose incubation, we also found that fructose-1-phosphate, a product of fructokinase-mediated fructose metabolism, also stimulated AMPD activity (Fig. 5C, right). 1 UNIPROT:P40713 activates fructose metabolic process GO:0006000 Protein 5e75752e-ae96-11ec-a61d-0050569a1f61 PMCPMC8019370 Briefly, fructose is phosphorylated into fructose 1-phosphate in a reaction catalyzed by fructokinase primarily during fructose metabolism and this reaction decreases the levels of intracellular phosphate and ATP [13]. 1 MESH:D008070 activates fructose metabolic process GO:0006000 Phenotype 5c93c848-c9e0-11ee-9aaa-0050569a1f61 10.1016/j.ijbiomac.2022.09.231 Interestingly, Fuc treatment also attenuated LPS-induced fructose metabolism in brain tissue by increasing fructose residues and reducing uric acid (UA) content (Fig. 10E and F,P< 0.05). 1 MESH:D000860 activates fructose metabolic process GO:0006000 Phenotype ffb172a8-c8de-11ee-b346-0050569a791b PMC10196606 "In fact, hypoxia stimulates fructose metabolism in astrocytes [54]." 1 IP:IPR001312 activates fructose metabolic process GO:0006000 ProteinFamily b0065e6c-5c1b-11e7-8c5f-001a4ae51246 PMC5452156 Although, the low-activity KHK (KHK-A) isoform is expressed in adipocytes [103] and alternative hexokinase-mediated fructose metabolism takes part in adipose tissue, it is more reasonable to imply that the observed fructose-mediated metabolic effects are triggered by KHK-C-dependent metabolism in the liver. 1 UNIPROT:P42685 activates fructose metabolic process GO:0006000 Protein 3495ca2a-72cf-11ee-add2-0050569a791b 10.1007/s13562-023-00850-4 FRK-mediated fructose metabolism and shifting of carbon flux to storage starch are crucial during the early stages of tuber development (Renz and Stitt 2003). 1 GO:0006001 activates fructose metabolic process GO:0006000 Phenotype f1c025b2-0533-11f0-bb39-0050569a791b 10.1016/j.jbc.2024.107538 Collectively, the divergence of fructose catabolism from the glycolytic pathway and the lack of control of KHK activity lead to poorly regulated fructose metabolism. 1 PUBCHEM:6816 inhibits fructose metabolic process GO:0006000 Chemical 838d2682-352c-11e8-b868-001a4a160176 27995280 The increased food intake was attributed to the rapid initial steps of fructose metabolism in the brain, provoking an immediate drop in the ATP/AMP ratio, increased AMPK activity, decreased acetyl-CoA-carboxylase activity, and malonyl–CoA amount in the hypothalamus (Cha et al.28). 1 FPLX:HIF activates fructose metabolic process GO:0006000 ProteinFamily 182ff670-5c43-11e7-bcb7-001a4ae51246 PMC5148111 Under hypoxia, the HIFα dependency of induction of a SF3B1 signal pathway enhances activation of fructose metabolism. 1 UNIPROT:Q9NP71 activates fructose metabolic process GO:0006000 Protein 618a8332-c8c3-11ee-ae05-0050569a1f61 10.1016/j.jnutbio.2022.109224 In spite of the strong evidence that ChREBP mediates some aspects of fructose metabolism in the liver, its role in fructose-induced metabolic dysfunction is complex. 1 UNIPROT:Q9NP71 inhibits fructose metabolic process GO:0006000 Protein d0c1b61a-7d07-11ee-add2-0050569a791b 10.1007/s00011-023-01707-1 It remains unclear, however, whether the imbalance in fructose metabolism induced by ChREBP deficiency causes GI symptoms by influencing intestinal microbial composition and immune responses. 1 UNIPROT:Q9NP71 activates fructose metabolic process GO:0006000 Protein 736f6e60-5c2c-11e7-9833-001a4ae51246 PMC5331612 ChREBP potentially regulates both intestinal and hepatic fructose metabolism. 1 CHEBI:29864 activates fructose metabolic process GO:0006000 Chemical b228c008-c6d7-11ee-b346-0050569a791b 10.1016/j.focha.2023.100463 Both yeast and lactic acid bacteria produce mannitol, which is the end product of fructose metabolism (Jia & Ma, 2023). 1 CHEBI:16474 inhibits fructose metabolic process GO:0006000 Chemical 9d142ba0-ca5d-11e5-8050-001a4ae51246 PMC140239 "Many are known or predicted to function in carbohydrate metabolism, such as the synthesis (e.g.,tps1) or degradation (ntp1) of the stress-protectant sugar trehalose, the generation of NADPH reducing equivalents (zwf1and SPAC3C7.13c, which encode glucose-6-phosphate dehydrogenases), and fructose metabolism (SPBC24C6.09c, encoding a predicted fructose-6-phosphate phosphoketolase)." 1 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical f5f20c74-f543-11eb-bcfb-001a4a160176 29496262 " Sanchez-Lozada C. Cicerchi Uric acid stimulates fructokinase and accelerates fructose metabolism in the development of fatty liver PLoS One 7 10 2012 e47948 54 M. Mazzali J. Hughes Y.G." 1 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical 2ee72e3a-bc38-11e5-ac4e-001a4ae51246 PMC3480441 This study provides the first evidence that uric acid can directly regulate fructose metabolism. 1 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical a7952c18-3c7d-11f0-8978-0050569a1f61 10.1016/j.sajb.2022.05.011 Uric acid stimulates fructokinase and accelerates fructose metabolism in the development of fatty liver. 1 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical 1a9aef0a-3791-11e6-aaca-001a4ae51246 PMC4850405 Fructose drives uric acid production in the placenta Given that fructose metabolism drives uric acid production in the liver (Fig. 2a)1, we wondered whether a similar effect occurred in the placentas of HFrD-fed mice. 1 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical d643934c-bbe0-11e5-8abe-001a4ae51246 10.1016/j.metabol.2011.04.001 In addition, uric acid is a major byproduct of fructose metabolism and may be responsible for some of its metabolic effects; and vitamin C and antioxidants can also block many of the proinflammatory effects of uric acid on various cell types[18]. 1 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical a7282e7c-67f7-11e8-8329-001a4a160176 PMC5893377 " Sanchez-Lozada C. Cicerchi N. Li C.A. Roncal-Jimenez T. Ishimoto Uric Acid stimulates fructokinase and accelerates fructose metabolism in the development of Fatty liver PLoS One 7 2012 e47948 [34] L.G." 1 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical 9b39652c-dca7-11ea-a56f-001a4a160175 PMC7286363 " Sanchez-Lozada C. Cicerchi Uric acid stimulates fructokinase and accelerates fructose metabolism in the development of fatty liver PLoS One 7 10 2012 e47948 54 M. Mazzali J. Hughes Y.G." 1 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical 17917cc0-3791-11e6-8a17-001a4ae51247 PMC4850171 An increase in uric acid in the liver may stimulate fructose metabolism [59•] and lipogenic enzymes [60•] and may thus contribute to further enhance de novo lipogenesis. 1 CHEBI:27226 activates fructose metabolic process GO:0006000 Chemical 3a784a99-f588-11eb-93fd-001a4a160176 30852460 Uric acid is the ultimate product of fructose metabolism in the liver. 1 MESH:D005985 activates fructose metabolic process GO:0006000 Phenotype 6e04d216-c8ea-11e5-891f-001a4ae51247 PMC2538689 Glyceraldehyde, on the other hand, is produced from the breakdown of F1P (fructose 1-phosphate), connecting fructose metabolism to that of glycerol and to glycolysis and gluconeogenesis. 1 MESH:D005985 activates fructose metabolic process GO:0006000 Phenotype 8398d094-c8ec-11e5-9faa-001a4ae51247 18537936 Glyceraldehyde is a key intermediate of fructose metabolism and a precursor for arg-pyrimidine (Tessier et al. 1999). 1 MESH:D005632 inhibits fructose metabolic process GO:0006000 Phenotype 28bd75b4-5c32-11e7-8c5f-001a4ae51246 PMC5264275 [109] Extrahepatic cells do not express fructokinase and extrahepatic hexokinase has a high Km for fructose, restricting almost all fructose metabolism to the liver. 1 MESH:D005632 inhibits fructose metabolic process GO:0006000 Phenotype 8ca3b61a-ab20-11e6-ab72-001a4ae51246 PMC5025922 [214] Extrahepatic cells do not express fructokinase and extrahepatic hexokinase has a high Km for fructose, restricting almost all fructose metabolism to the liver. 1 MESH:D005632 activates fructose metabolic process GO:0006000 Phenotype 8250cd84-bc00-11e5-9b9d-001a4ae51247 10.1016/j.bbrc.2012.02.001 Fructose increased expression of fructose metabolism-related genes in the liver in all strains The effects of fructose-feeding on liver characteristics were examined (Table 2). 1 MESH:D005632 activates fructose metabolic process GO:0006000 Phenotype 20196856-c7cd-11ee-ae05-0050569a1f61 PMC10752375 Hepatic fructose metabolism can be upregulated by endogenous fructose produced, via the polyol pathway, from glucose as a substrate [11]. 1 MESH:D005632 activates fructose metabolic process GO:0006000 Phenotype eb28c958-c46e-11e5-9cc6-001a4ae51246 PMC3957730 "Furthermore, significant upregulation of thepfkBtranscript (glpR-pfkBoperon and monocistronic transcript) as well as thefbatranscript was observed in the presence of fructose, which was reflected at the enzyme level by 3- and 8-fold-higher 1-PFK and FBA activities, respectively, supporting the function of both enzymes in fructose metabolism (123)." 1 UNIPROT:P13866 activates fructose metabolic process GO:0006000 Protein be439e0c-352e-11e9-913f-001a4a160175 PMC6095711 Moreover, keratinocytes expressGlut5, SGLT1(Fig. S1d–e), and ketohexokinase which should allow for fructose metabolism to occur. 1 GO:0032445 activates fructose metabolic process GO:0006000 Phenotype fc79fc9e-c6b9-11ee-9aaa-0050569a1f61 10.1016/j.cmet.2023.09.011 Fructose uptake in adipocytes mediated fructose metabolism and the accumulation of glycolytic intermediates, thereby activating mTORC1 signaling to induce leptin expression. 1 PF:PF02974 inhibits fructose metabolic process GO:0006000 ProteinFamily 23382dd0-351d-11e9-ab56-001a4a160175 PMC6088158 These data support our model that (i) GlpR is a repressor of fructose metabolism when fructose is not present in the environment and (ii) the two C/A-rich motifs of thefbapromoter region are required for GlpR-dependent regulation.