scholarly journals Fructose Metabolism in Cancer

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2635
Author(s):  
Nils Krause ◽  
Andre Wegner
Keyword(s):  
Metabolic Pathways ◽  
Polyol Pathway ◽  
Cancer Cell Proliferation ◽  
Nucleotide Synthesis ◽  
Metabolic Intermediates ◽  
Fructose Metabolism ◽  
Fructose Intake ◽  
Endogenous Production ◽  
Increased Risk ◽  
Dietary Fructose

The interest in fructose metabolism is based on the observation that an increased dietary fructose consumption leads to an increased risk of obesity and metabolic syndrome. In particular, obesity is a known risk factor to develop many types of cancer and there is clinical and experimental evidence that an increased fructose intake promotes cancer growth. The precise mechanism, however, in which fructose induces tumor growth is still not fully understood. In this article, we present an overview of the metabolic pathways that utilize fructose and how fructose metabolism can sustain cancer cell proliferation. Although the degradation of fructose shares many of the enzymes and metabolic intermediates with glucose metabolism through glycolysis, glucose and fructose are metabolized differently. We describe the different metabolic fates of fructose carbons and how they are connected to lipogenesis and nucleotide synthesis. In addition, we discuss how the endogenous production of fructose from glucose via the polyol pathway can be beneficial for cancer cells.

scholarly journals Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides

Cancers ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 688 ◽  
Author(s):  
Elodie Villa ◽  
Eunus Ali ◽  
Umakant Sahu ◽  
Issam Ben-Sahra
Keyword(s):  
Cancer Cells ◽  
Tumor Suppressors ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Cancer Cell Proliferation ◽  
Nucleotide Synthesis ◽  
Nucleotide Pools ◽  
Molecular Determinants ◽  
Target Cancer

Cancer cells exhibit a dynamic metabolic landscape and require a sufficient supply of nucleotides and other macromolecules to grow and proliferate. To meet the metabolic requirements for cell growth, cancer cells must stimulate de novo nucleotide synthesis to obtain adequate nucleotide pools to support nucleic acid and protein synthesis along with energy preservation, signaling activity, glycosylation mechanisms, and cytoskeletal function. Both oncogenes and tumor suppressors have recently been identified as key molecular determinants for de novo nucleotide synthesis that contribute to the maintenance of homeostasis and the proliferation of cancer cells. Inactivation of tumor suppressors such as TP53 and LKB1 and hyperactivation of the mTOR pathway and of oncogenes such as MYC, RAS, and AKT have been shown to fuel nucleotide synthesis in tumor cells. The molecular mechanisms by which these signaling hubs influence metabolism, especially the metabolic pathways for nucleotide synthesis, continue to emerge. Here, we focus on the current understanding of the molecular mechanisms by which oncogenes and tumor suppressors modulate nucleotide synthesis in cancer cells and, based on these insights, discuss potential strategies to target cancer cell proliferation.

Fructose metabolism in the udders of dairy cows

1959 ◽  
Vol 197 (3) ◽  
pp. 677-680 ◽  
Author(s):  
Jack R. Luick ◽  
Max Kleiber ◽  
James M. Lucas
Keyword(s):  
Metabolic Pathways ◽  
Milk Protein ◽  
Enzyme System ◽  
Principal Direction ◽  
Mammary Tissue ◽  
Milk Products ◽  
Metabolic Intermediates ◽  
Fructose Metabolism ◽  
Metabolic Reactions ◽  
The One

The metabolism of fructose by mammary tissue was studied by infusing U-C14 fructose into the one quarter of a lactating cow's udder. Comparison of specific activities of milk products isolated from the injected and uninjected quarters showed that fructose, unlike glucose, was not converted to lactose by mammary tissue. However, fructose was oxidized in the udder to metabolic intermediates which lead to the synthesis of milk protein, butterfat, citrate and CO2. It appeared that little fructose C14 was absorbed by mammary tissue. These results were discussed with regard to the known metabolic pathways of fructose metabolism. It is postulated that an active fructokinase enzyme system functions in mammary tissue and further, that the principal direction of metabolic reactions in the udder favors catabolism of hexose rather than its synthesis.

scholarly journals Fructose reprogrammes glutamine-dependent oxidative metabolism to support LPS-induced inflammation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicholas Jones ◽  
Julianna Blagih ◽  
Fabio Zani ◽  
April Rees ◽  
David G. Hill ◽  
...  
Keyword(s):  
Oxidative Metabolism ◽  
Mononuclear Phagocytes ◽  
Alcoholic Fatty Liver ◽  
Lps Challenge ◽  
Fructose Intake ◽  
Mouse Macrophages ◽  
Dietary Fructose ◽  
Monocytes And Macrophages ◽  
Developed World

AbstractFructose intake has increased substantially throughout the developed world and is associated with obesity, type 2 diabetes and non-alcoholic fatty liver disease. Currently, our understanding of the metabolic and mechanistic implications for immune cells, such as monocytes and macrophages, exposed to elevated levels of dietary fructose is limited. Here, we show that fructose reprograms cellular metabolic pathways to favour glutaminolysis and oxidative metabolism, which are required to support increased inflammatory cytokine production in both LPS-treated human monocytes and mouse macrophages. A fructose-dependent increase in mTORC1 activity drives translation of pro-inflammatory cytokines in response to LPS. LPS-stimulated monocytes treated with fructose rely heavily on oxidative metabolism and have reduced flexibility in response to both glycolytic and mitochondrial inhibition, suggesting glycolysis and oxidative metabolism are inextricably coupled in these cells. The physiological implications of fructose exposure are demonstrated in a model of LPS-induced systemic inflammation, with mice exposed to fructose having increased levels of circulating IL-1β after LPS challenge. Taken together, our work underpins a pro-inflammatory role for dietary fructose in LPS-stimulated mononuclear phagocytes which occurs at the expense of metabolic flexibility.

scholarly journals Retinal Redox Stress and Remodeling in Cardiometabolic Syndrome and Diabetes

2010 ◽  
Vol 3 (6) ◽  
pp. 392-403 ◽  
Author(s):  
Ying Yang ◽  
Melvin R. Hayden ◽  
Susan Sowers ◽  
Sarika V. Bagree ◽  
James R. Sowers
Keyword(s):  
Metabolic Pathways ◽  
Tissue Injury ◽  
Disease Process ◽  
Polyol Pathway ◽  
The United States ◽  
Redox Stress ◽  
Blood Retinal Barrier ◽  
Cardiometabolic Syndrome ◽  
Hexosamine Pathway ◽  
Pathway Flux

Diabetic retinopathy (DR) is a significant cause of global blindness; a major cause of blindness in the United States in people aged between 20–74. There is emerging evidence that retinopathy is initiated and propagated by multiple metabolic toxicities associated with excess production of reactive oxygen species (ROS). The four traditional metabolic pathways involved in the development of DR include: increased polyol pathway flux, advanced glycation end-product formation, activation of protein kinase Cisoforms and hexosamine pathway flux. These pathways individually and synergisticallycontribute to redox stress with excess ROS resulting in retinal tissue injury resulting in significant microvascular blood retinal barrier remodeling. The toxicity of hyperinsulinemia, hyperglycemia, hypertension, dyslipidemia, increased cytokines and growth factors, in conjunction with redox stress, contribute to the development and progression of DR. Redox stress contributes to the development and progression of abnormalities of endothelial cells and pericytes in DR. This review focuses on the ultrastructural observations of the blood retinal barrier including the relationship between the endothelial cell and pericyte remodeling in young nine week old Zucker obese (fa/ fa) rat model of obesity; cardiometabolic syndrome, and the 20 week old alloxan induced diabetic porcine model. Preventing or delaying the blindness associated with these intersecting abnormal metabolic pathways may be approached through strategies targeted to reduction of tissue inflammation and oxidative—redox stress. Understanding these abnormal metabolic pathways and the accompanying redox stress and remodeling mayprovide both the clinician and researcher a new concept of approaching this complicated disease process

scholarly journals Mitochondrial Transfer in Cancer: A Comprehensive Review

2021 ◽  
Vol 22 (6) ◽  
pp. 3245
Author(s):  
Luca X. Zampieri ◽  
Catarina Silva-Almeida ◽  
Justin D. Rondeau ◽  
Pierre Sonveaux
Keyword(s):  
Cancer Cells ◽  
Cancer Cell ◽  
Metabolic Pathways ◽  
Current Knowledge ◽  
Cancer Cell Proliferation ◽  
Tunneling Nanotubes ◽  
Comprehensive Review ◽  
Cancer Cell Death ◽  
Mitochondrial Transfer ◽  
Metabolic Activities

Depending on their tissue of origin, genetic and epigenetic marks and microenvironmental influences, cancer cells cover a broad range of metabolic activities that fluctuate over time and space. At the core of most metabolic pathways, mitochondria are essential organelles that participate in energy and biomass production, act as metabolic sensors, control cancer cell death, and initiate signaling pathways related to cancer cell migration, invasion, metastasis and resistance to treatments. While some mitochondrial modifications provide aggressive advantages to cancer cells, others are detrimental. This comprehensive review summarizes the current knowledge about mitochondrial transfers that can occur between cancer and nonmalignant cells. Among different mechanisms comprising gap junctions and cell-cell fusion, tunneling nanotubes are increasingly recognized as a main intercellular platform for unidirectional and bidirectional mitochondrial exchanges. Understanding their structure and functionality is an important task expected to generate new anticancer approaches aimed at interfering with gains of functions (e.g., cancer cell proliferation, migration, invasion, metastasis and chemoresistance) or damaged mitochondria elimination associated with mitochondrial transfer.

scholarly journals Dietary Fructose Metabolism By Splanchnic Organs: Size Matters

2018 ◽  
Vol 27 (3) ◽  
pp. 483-485 ◽  
Author(s):  
Javier T. Gonzalez ◽  
James A. Betts
Keyword(s):  
Fructose Metabolism ◽  
Dietary Fructose

scholarly journals Chronic Inhibition of Mitochondrial Dihydrolipoamide Dehydrogenase (DLDH) as an Approach to Managing Diabetic Oxidative Stress

Antioxidants ◽  
2019 ◽  
Vol 8 (2) ◽  
pp. 32 ◽  
Author(s):  
Xiaojuan Yang ◽  
Jing Song ◽  
Liang-Jun Yan
Keyword(s):  
Oxidative Stress ◽  
Type 2 Diabetes ◽  
Metabolic Pathways ◽  
Reactive Nitrogen Species ◽  
Dihydrolipoamide Dehydrogenase ◽  
Redox Enzyme ◽  
Atp Production ◽  
Metabolic Intermediates ◽  
Novel Approach

Mitochondrial dihydrolipoamide dehydrogenase (DLDH) is a redox enzyme involved in decarboxylation of pyruvate to form acetyl-CoA during the cascade of glucose metabolism and mitochondrial adenine triphosphate (ATP) production. Depending on physiological or pathophysiological conditions, DLDH can either enhance or attenuate the production of reactive oxygen species (ROS) and reactive nitrogen species. Recent research in our laboratory has demonstrated that inhibition of DLDH induced antioxidative responses and could serve as a protective approach against oxidative stress in stroke injury. In this perspective article, we postulated that chronic inhibition of DLDH could also attenuate oxidative stress in type 2 diabetes. We discussed DLDH-involving mitochondrial metabolic pathways and metabolic intermediates that could accumulate upon DLDH inhibition and their corresponding roles in abrogating oxidative stress in diabetes. We also discussed a couple of DLDH inhibitors that could be tested in animal models of type 2 diabetes. It is our belief that DLDH inhibition could be a novel approach to fighting type 2 diabetes.

scholarly journals Metabolomic Links Between Sweetened Beverage Intake and Obesity (OR31-05-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chao-Qiang Lai ◽  
Reiko Ichikawa ◽  
Bingjie Zhou ◽  
Laurence Parnell ◽  
Sabrina Noel ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Metabolic Pathways ◽  
Enrichment Analysis ◽  
Health Study ◽  
Pathway Enrichment Analysis ◽  
Linear Regression Models ◽  
Obesity Risk ◽  
Pathway Enrichment ◽  
Sweetened Beverage ◽  
Increased Risk

Abstract Objectives Sweetened beverage (SB) consumption is highly associated with obesity, but the mechanism underlying this correlation is not understood. Our objective was to examine metabolomic links between SB intake and obesity to understand metabolic mechanisms. Methods We examined the association of plasma metabolomic profiles with SB intake and obesity risk in 782 participants, aged 45–75y, in the Boston Puerto Rican Health Study (BPRHS) using linear regression models, controlling for potential confounding factors. Based on identified metabolites, we conducted pathway enrichment analysis to identify potential metabolic pathways that link SB intake and obesity risk. Genetic variants in identified metabolic pathways were examined for their interaction with SB intake on metabolites of interest and obesity. Interactions between SB and genotypes on obesity were evaluated for replication in the Framingham Heart Study (FHS). Results In BPRHS, SB intake was highly correlated with BMI (β = 0.455, P < 0.05). Among 526 measurable metabolites, 109 metabolites showed significant correlation with SB intake and 170 metabolites with BMI (P < 0.05); and 43 were correlated with both SB intake and BMI. Pathway enrichment analysis identified two metabolic pathways: phosphatidylethanolamine (PE) and lysophospholipid pathways linking SB intake and obesity, after correction for multiple testing. Focusing on the PE pathway, we identified 12 SNPs in nine genes that were significantly associated with BMI. At least four genetic variants showed suggestive interaction with SB intake on obesity risk and obesity-associated metabolites. In particular, CC carriers of rs4646360 in the PEMT (Phosphatidylethanolamine N-Methyltransferase) gene had increased risk of obesity when consuming SB. We replicated this finding in the FHS study. Conclusions We identified two key metabolic pathways linking SB intake to obesity, revealing potential mechanisms by which SB intake increases the risk of obesity. The interaction between genetic variants in the identified pathway and SB intake on obesity and obesity-associated metabolites further supports the mechanism. Funding Sources This work was funded by the US Department of Agriculture, under agreement no. 8050-51,000-098-00D, and NIH grants P01 AG023394, P50 HL105185, and R01 AG027087.

scholarly journals Evaluation of an aldo-keto reductase gene signature with prognostic significance in colon cancer via activation of epithelial to mesenchymal transition and the p70S6K pathway

2020 ◽  
Vol 41 (9) ◽  
pp. 1219-1228
Author(s):  
Seçil Demirkol Canlı ◽  
Esin Gülce Seza ◽  
Ilir Sheraj ◽  
Ismail Gömçeli ◽  
Nesrin Turhan ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Metabolic Pathways ◽  
Epithelial To Mesenchymal Transition ◽  
Ex Vivo ◽  
Prognostic Significance ◽  
Distal Colon ◽  
Polyol Pathway ◽  
Gene Signature ◽  
Nutrient Sensing ◽  
Mesenchymal Transition

Abstract AKR1B1 and AKR1B10, members of the aldo-keto reductase family of enzymes that participate in the polyol pathway of aldehyde metabolism, are aberrantly expressed in colon cancer. We previously showed that high expression of AKR1B1 (AKR1B1HIGH) was associated with enhanced motility, inflammation and poor clinical outcome in colon cancer patients. Using publicly available datasets and ex vivo gene expression analysis (n = 51, Ankara cohort), we have validated our previous in silico finding that AKR1B1HIGH was associated with worse overall survival (OS) compared with patients with low expression of AKR1B1 (AKR1B1LOW) samples. A combined signature of AKR1B1HIGH and AKR1B10LOW was significantly associated with worse recurrence-free survival (RFS) in microsatellite stable (MSS) patients and in patients with distal colon tumors as well as a higher mesenchymal signature when compared with AKR1B1LOW/AKR1B10HIGH tumors. When the patients were stratified according to consensus molecular subtypes (CMS), AKR1B1HIGH/AKR1B10LOW samples were primarily classified as CMS4 with predominantly mesenchymal characteristics while AKR1B1LOW/AKR1B10HIGH samples were primarily classified as CMS3 which is associated with metabolic deregulation. Reverse Phase Protein Array carried out using protein samples from the Ankara cohort indicated that AKR1B1HIGH/AKR1B10LOW tumors showed aberrant activation of metabolic pathways. Western blot analysis of AKR1B1HIGH/AKR1B10LOW colon cancer cell lines also suggested aberrant activation of nutrient-sensing pathways. Collectively, our data suggest that the AKR1B1HIGH/AKR1B10LOW signature may be predictive of poor prognosis, aberrant activation of metabolic pathways, and can be considered as a novel biomarker for colon cancer prognostication.

scholarly journals The importance of serine metabolism in cancer

2016 ◽  
Vol 214 (3) ◽  
pp. 249-257 ◽  
Author(s):  
Katherine R. Mattaini ◽  
Mark R. Sullivan ◽  
Matthew G. Vander Heiden
Keyword(s):  
Cell Proliferation ◽  
Amino Acid ◽  
Cancer Cells ◽  
De Novo ◽  
Redox Homeostasis ◽  
Cancer Cell Proliferation ◽  
Acid Transport ◽  
Nucleotide Synthesis ◽  
Serine Metabolism

Serine metabolism is frequently dysregulated in cancers; however, the benefit that this confers to tumors remains controversial. In many cases, extracellular serine alone is sufficient to support cancer cell proliferation, whereas some cancer cells increase serine synthesis from glucose and require de novo serine synthesis even in the presence of abundant extracellular serine. Recent studies cast new light on the role of serine metabolism in cancer, suggesting that active serine synthesis might be required to facilitate amino acid transport, nucleotide synthesis, folate metabolism, and redox homeostasis in a manner that impacts cancer.

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