Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis.
Activators
Cancer
Glucose
Glycolysis
Inhibitors
Krebs cycle
Journal
Archives of toxicology
ISSN: 1432-0738
Titre abrégé: Arch Toxicol
Pays: Germany
ID NLM: 0417615
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
01
11
2020
accepted:
04
01
2021
pubmed:
3
3
2021
medline:
4
11
2021
entrez:
2
3
2021
Statut:
ppublish
Résumé
A fundamental metabolic feature of cancerous tissues is high glucose consumption. The rate of glucose consumption in a cancer cell can be 10-15 times higher than in normal cells. Isolation and cultivation of tumor cells in vitro highlight properties that are associated with intensive glucose utilization, the presence of minimal oxidative metabolism, an increase in lactate concentrations in the culture medium and a reduced rate of oxygen consumption. Although glycolysis is suggested as a general feature of malignant cells and recently identified as a possible contributing factor to tumor progression, several studies highlight distinct metabolic characteristics in some tumors, including a relative decrease in avidity compared to glucose and/or a glutamine dependency of lactate and even proliferative tumor cells. The aim of this review is to determine the particularities in the energy metabolism of cancer cells, focusing on the main nutritional substrates, such as glucose and glutamine, evaluating lactate dehydrogenase as a potential marker of malignancy and estimating activators and inhibitors in cancer treatment.
Identifiants
pubmed: 33649975
doi: 10.1007/s00204-021-02974-9
pii: 10.1007/s00204-021-02974-9
doi:
Substances chimiques
Glutamine
0RH81L854J
L-Lactate Dehydrogenase
EC 1.1.1.27
Glucose
IY9XDZ35W2
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1161-1178Références
Aguilar-Lopez BA, Moreno-Altamirano MMB, Dockrell HM, Duchen MR, Sanchez-Garcia FJ (2020) Mitochondria: an integrative hub coordinating circadian rhythms, metabolism, the microbiome, and immunity. Front Cell Dev Biol 8:51. https://doi.org/10.3389/fcell.2020.00051
doi: 10.3389/fcell.2020.00051
pubmed: 32117978
pmcid: 7025554
Akram M (2014) Citric acid cycle and role of its intermediates in metabolism. Cell Biochem Biophys 68(3):475–478. https://doi.org/10.1007/s12013-013-9750-1
doi: 10.1007/s12013-013-9750-1
pubmed: 24068518
Anderson NM, Mucka P, Kern JG, Feng H (2018) The emerging role and targetability of the TCA cycle in cancer metabolism. Protein Cell 9(2):216–237. https://doi.org/10.1007/s13238-017-0451-1
doi: 10.1007/s13238-017-0451-1
pubmed: 28748451
Andrzejewski S, Gravel SP, Pollak M, St-Pierre J (2014) Metformin directly acts on mitochondria to alter cellular bioenergetics. Cancer Metab 2:12. https://doi.org/10.1186/2049-3002-2-12
doi: 10.1186/2049-3002-2-12
pubmed: 25184038
pmcid: 4147388
Anjum F, Shakoori AR (1997) Sublethal effects of hexavalent chromium on the body growth rate and liver function enzymes of phenobarbitone-pretreated and promethazine-pretreated rabbits. J Environ Pathol Toxicol Oncol 16(1):51–59
pubmed: 9256933
Artioli GG, Sale C, Jones RL (2019) Carnosine in health and disease. Eur J Sport Sci 19(1):30–39. https://doi.org/10.1080/17461391.2018.1444096
doi: 10.1080/17461391.2018.1444096
pubmed: 29502490
Auger C, Lemire J, Cecchini D, Bignucolo A, Appanna VD (2011) The metabolic reprogramming evoked by nitrosative stress triggers the anaerobic utilization of citrate in Pseudomonas fluorescens. PLoS ONE 6(12):e28469. https://doi.org/10.1371/journal.pone.0028469
doi: 10.1371/journal.pone.0028469
pubmed: 22145048
pmcid: 3228765
Babu R, Eaton S, Drake DP, Spitz L, Pierro A (2001) Glutamine and glutathione counteract the inhibitory effects of mediators of sepsis in neonatal hepatocytes. J Pediatr Surg 36(2):282–286. https://doi.org/10.1053/jpsu.2001.20690
doi: 10.1053/jpsu.2001.20690
pubmed: 11172416
Baguet A, Bourgois J, Vanhee L, Achten E, Derave W (2010) Important role of muscle carnosine in rowing performance. J Appl Physiol (1985) 109(4):1096–1101. https://doi.org/10.1152/japplphysiol.00141.2010
doi: 10.1152/japplphysiol.00141.2010
Bansal P, Sharma P, Goyal V (2002) Impact of lead and cadmium on enzyme of citric acid cycle in germinating pea seeds. Biol Plant 45(1):125–127. https://doi.org/10.1023/a:1015173112842
doi: 10.1023/a:1015173112842
Bao Y, Ding S, Cheng J, Liu Y, Wang B, Xu H, Shen Y, Lyu J (2018) Carnosine inhibits the proliferation of human cervical gland carcinoma cells through inhibiting both mitochondrial bioenergetics and glycolysis pathways and retarding cell cycle progression. Integr Cancer Ther 17(1):80–91. https://doi.org/10.1177/1534735416684551
doi: 10.1177/1534735416684551
pubmed: 28008780
Bartkova J, Rezaei N, Liontos M, Karakaidos P, Kletsas D, Issaeva N, Vassiliou L-VF, Kolettas E et al (2006) Oncogene-induced senescence is part of the tumorigenesis barrier imposed by DNA damage checkpoints. Nature 444(7119):633–637. https://doi.org/10.1038/nature05268
doi: 10.1038/nature05268
pubmed: 17136093
Bayliak MM, Lylyk MP, Vytvytska OM, Lushchak VI (2016) Assessment of antioxidant properties of alpha-keto acids in vitro and in vivo. Eur Food Res Technol 242(2):179–188. https://doi.org/10.1007/s00217-015-2529-4
doi: 10.1007/s00217-015-2529-4
Berezhnoy DS, Stvolinsky SL, Lopachev AV, Devyatov AA, Lopacheva OM, Kulikova OI, Abaimov DA, Fedorova TN (2019) Carnosine as an effective neuroprotector in brain pathology and potential neuromodulator in normal conditions. Amino Acids 51(1):139–150. https://doi.org/10.1007/s00726-018-2667-7
doi: 10.1007/s00726-018-2667-7
pubmed: 30353356
Bjørklund G, Peana M, Maes M, Dadar M, Severin B (2020a) The glutathione system in Parkinson’s disease and its progression. Neurosci Biobehav Rev. https://doi.org/10.1016/j.neubiorev.2020.10.004
doi: 10.1016/j.neubiorev.2020.10.004
pubmed: 33068556
Bjørklund G, Tinkov AA, Hosnedlova B, Kizek R, Ajsuvakova OP, Chirumbolo S, Skalnaya MG, Peana M et al (2020b) The role of glutathione redox imbalance in autism spectrum disorder: a review. Free Radic Biol Med 160:149–162. https://doi.org/10.1016/j.freeradbiomed.2020.07.017
doi: 10.1016/j.freeradbiomed.2020.07.017
pubmed: 32745763
Bjørklund G, Doşa MD, Maes M, Dadar M, Frye RE, Peana M, Chirumbolo S (2021) The impact of glutathione metabolism in autism spectrum disorder. Pharmacol Res. https://doi.org/10.1016/j.phrs.2021.105437
doi: 10.1016/j.phrs.2021.105437
pubmed: 33493659
Breda CNdS, Davanzo GG, Basso PJ, Saraiva Câmara NO, Moraes-Vieira PMM (2019) Mitochondria as central hub of the immune system. Redox Biol 26:101255. https://doi.org/10.1016/j.redox.2019.101255
doi: 10.1016/j.redox.2019.101255
pubmed: 31247505
pmcid: 6598836
Brownsey RW, Zhande R, Boone AN (1997) Isoforms of acetyl-CoA carboxylase: structures, regulatory properties and metabolic functions. Biochem Soc Trans 25(4):1232–1238. https://doi.org/10.1042/bst0251232
doi: 10.1042/bst0251232
pubmed: 9449982
Bruce M, Constantin-Teodosiu D, Greenhaff PL, Boobis LH, Williams C, Bowtell JL (2001) Glutamine supplementation promotes anaplerosis but not oxidative energy delivery in human skeletal muscle. Am J Physiol Endocrinol Metab 280(4):E669–E675. https://doi.org/10.1152/ajpendo.2001.280.4.E669
doi: 10.1152/ajpendo.2001.280.4.E669
pubmed: 11254475
Brusilow SW, Koehler RC, Traystman RJ, Cooper AJ (2010) Astrocyte glutamine synthetase: importance in hyperammonemic syndromes and potential target for therapy. Neurotherapeutics 7(4):452–470. https://doi.org/10.1016/j.nurt.2010.05.015
doi: 10.1016/j.nurt.2010.05.015
pubmed: 20880508
pmcid: 2975543
Burns JS, Manda G (2017) Metabolic pathways of the Warburg effect in health and disease: perspectives of choice, chain or chance. Int J Mol Sci 18(12):2755. https://doi.org/10.3390/ijms18122755
doi: 10.3390/ijms18122755
pmcid: 5751354
Castelletto V, Edwards-Gayle CJC, Greco F, Hamley IW, Seitsonen J, Ruokolainen J (2019) Self-assembly, tunable hydrogel properties, and selective anti-cancer activity of a carnosine-derived lipidated peptide. ACS Appl Mater Interfaces 11(37):33573–33580. https://doi.org/10.1021/acsami.9b09065
doi: 10.1021/acsami.9b09065
pubmed: 31407889
pmcid: 7007010
Chae YK, Arya A, Malecek MK, Shin DS, Carneiro B, Chandra S, Kaplan J, Kalyan A et al (2016) Repurposing metformin for cancer treatment: current clinical studies. Oncotarget 7(26):40767–40780. https://doi.org/10.18632/oncotarget.8194
doi: 10.18632/oncotarget.8194
pubmed: 5130043
pmcid: 5130043
Cheng JY, Yang JB, Liu Y, Xu M, Huang YY, Zhang JJ, Cao P, Lyu JX et al (2019) Profiling and targeting of cellular mitochondrial bioenergetics: inhibition of human gastric cancer cell growth by carnosine. Acta Pharmacol Sin 40(7):938–948. https://doi.org/10.1038/s41401-018-0182-8
doi: 10.1038/s41401-018-0182-8
pubmed: 30560903
Choudhary C, Weinert BT, Nishida Y, Verdin E, Mann M (2014) The growing landscape of lysine acetylation links metabolism and cell signalling. Nat Rev Mol Cell Biol 15(8):536–550. https://doi.org/10.1038/nrm3841
doi: 10.1038/nrm3841
pubmed: 25053359
Ciccarone F, Di Leo L, Lazzarino G, Maulucci G, Di Giacinto F, Tavazzi B, Ciriolo MR (2020) Aconitase 2 inhibits the proliferation of MCF-7 cells promoting mitochondrial oxidative metabolism and ROS/FoxO1-mediated autophagic response. Br J Cancer 122(2):182–193. https://doi.org/10.1038/s41416-019-0641-0
doi: 10.1038/s41416-019-0641-0
pubmed: 31819175
Cook KM, Figg WD (2010) Angiogenesis inhibitors: current strategies and future prospects. CA Cancer J Clin 60(4):222–243. https://doi.org/10.3322/caac.20075
doi: 10.3322/caac.20075
pubmed: 20554717
pmcid: 2919227
Costello LC, Liu Y, Franklin RB, Kennedy MC (1997) Zinc inhibition of mitochondrial aconitase and its importance in citrate metabolism of prostate epithelial cells. J Biol Chem 272(46):28875–28881. https://doi.org/10.1074/jbc.272.46.28875
doi: 10.1074/jbc.272.46.28875
pubmed: 9360955
Crisponi G, Dean A, Di Marco V, Lachowicz JI, Nurchi VM, Remelli M, Tapparo A (2013) Different approaches to the study of chelating agents for iron and aluminium overload pathologies. Anal Bioanal Chem 405(2–3):585–601. https://doi.org/10.1007/s00216-012-6468-7
doi: 10.1007/s00216-012-6468-7
pubmed: 23096940
Dadsetan S, Kukolj E, Bak LK, Sørensen M, Ott P, Vilstrup H, Schousboe A, Keiding S et al (2013) Brain alanine formation as an ammonia-scavenging pathway during hyperammonemia: effects of glutamine synthetase inhibition in rats and astrocyte-neuron co-cultures. J Cereb Blood Flow Metab 33(8):1235–1241. https://doi.org/10.1038/jcbfm.2013.73
doi: 10.1038/jcbfm.2013.73
pubmed: 23673435
pmcid: 3734774
Degli Esposti D, Hamelin J, Bosselut N, Saffroy R, Sebagh M, Pommier A, Martel C, Lemoine A (2012) Mitochondrial roles and cytoprotection in chronic liver injury. Biochem Res Int 2012:387626. https://doi.org/10.1155/2012/387626
doi: 10.1155/2012/387626
pubmed: 22745910
pmcid: 3382253
Demarin V, Podobnik SS, Storga-Tomic D, Kay G (2004) Treatment of Alzheimer’s disease with stabilized oral nicotinamide adenine dinucleotide: a randomized, double-blind study. Drugs Exp Clin Res 30(1):27–33
pubmed: 15134388
Devic S (2016) Warburg effect—a consequence or the cause of carcinogenesis? J Cancer 7(7):817–822. https://doi.org/10.7150/jca.14274
doi: 10.7150/jca.14274
pubmed: 27162540
pmcid: 4860798
Devin A, Rigoulet M (2007) Mechanisms of mitochondrial response to variations in energy demand in eukaryotic cells. Am J Physiol Cell Physiol 292(1):C52–C58. https://doi.org/10.1152/ajpcell.00208.2006
doi: 10.1152/ajpcell.00208.2006
pubmed: 16943247
Diaz-Ruiz R, Rigoulet M, Devin A (2011) The Warburg and Crabtree effects: on the origin of cancer cell energy metabolism and of yeast glucose repression. Biochim Biophys Acta 1807(6):568–576. https://doi.org/10.1016/j.bbabio.2010.08.010
doi: 10.1016/j.bbabio.2010.08.010
pubmed: 20804724
Ding M, Jiao G, Shi H, Chen Y (2018) Investigations on in vitro anti-carcinogenic potential of L-carnosine in liver cancer cells. Cytotechnology 70(1):163–167. https://doi.org/10.1007/s10616-017-0123-2
doi: 10.1007/s10616-017-0123-2
pubmed: 28752496
Dinic J, Efferth T, Garcia-Sosa AT, Grahovac J, Padron JM, Pajeva I, Rizzolio F, Saponara S et al (2020) Repurposing old drugs to fight multidrug resistant cancers. Drug Resist Updat 52:100713. https://doi.org/10.1016/j.drup.2020.100713
doi: 10.1016/j.drup.2020.100713
pubmed: 32615525
Evans JM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD (2005) Metformin and reduced risk of cancer in diabetic patients. BMJ 330(7503):1304–1305. https://doi.org/10.1136/bmj.38415.708634.F7
doi: 10.1136/bmj.38415.708634.F7
pubmed: 558205
pmcid: 558205
Everts B, Amiel E, Huang SC, Smith AM, Chang CH, Lam WY, Redmann V, Freitas TC et al (2014) TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKvarepsilon supports the anabolic demands of dendritic cell activation. Nat Immunol 15(4):323–332. https://doi.org/10.1038/ni.2833
doi: 10.1038/ni.2833
pubmed: 24562310
pmcid: 4358322
Fei B, Ji F, Chen X, Liu Z, Li S, Mo Z, Fang X (2016) Expression and clinical significance of Beclin-1 in gastric cancer tissues of various clinical stages. Oncol Lett 11(3):2271–2277. https://doi.org/10.3892/ol.2016.4183
doi: 10.3892/ol.2016.4183
pubmed: 26998161
pmcid: 4774614
Fernie AR, Carrari F, Sweetlove LJ (2004) Respiratory metabolism: glycolysis, the TCA cycle and mitochondrial electron transport. Curr Opin Plant Biol 7(3):254–261. https://doi.org/10.1016/j.pbi.2004.03.007
doi: 10.1016/j.pbi.2004.03.007
pubmed: 15134745
Fleming RE, Ponka P (2012) Iron overload in human disease. N Engl J Med 366(4):348–359. https://doi.org/10.1056/NEJMra1004967
doi: 10.1056/NEJMra1004967
pubmed: 22276824
Fricker RA, Green EL, Jenkins SI, Griffin SM (2018) The influence of nicotinamide on health and disease in the central nervous system. Int J Tryptophan Res 11:1178646918776658. https://doi.org/10.1177/1178646918776658
doi: 10.1177/1178646918776658
pubmed: 29844677
pmcid: 5966847
Garaude J, Acin-Perez R, Martinez-Cano S, Enamorado M, Ugolini M, Nistal-Villan E, Hervas-Stubbs S, Pelegrin P et al (2016) Mitochondrial respiratory-chain adaptations in macrophages contribute to antibacterial host defense. Nat Immunol 17(9):1037–1045. https://doi.org/10.1038/ni.3509
doi: 10.1038/ni.3509
pubmed: 27348412
pmcid: 4994870
Gibala MJ, MacLean DA, Graham TE, Saltin B (1998) Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise. Am J Physiol 275(2):E235–E242. https://doi.org/10.1152/ajpendo.1998.275.2.E235
doi: 10.1152/ajpendo.1998.275.2.E235
pubmed: 9688624
Gibson GE, Sheu KF, Blass JP (1998) Abnormalities of mitochondrial enzymes in Alzheimer disease. J Neural Transm (Vienna) 105(8–9):855–870. https://doi.org/10.1007/s007020050099
doi: 10.1007/s007020050099
Green CR, Wallace M, Divakaruni AS, Phillips SA, Murphy AN, Ciaraldi TP, Metallo CM (2016) Branched-chain amino acid catabolism fuels adipocyte differentiation and lipogenesis. Nat Chem Biol 12(1):15–21. https://doi.org/10.1038/nchembio.1961
doi: 10.1038/nchembio.1961
pubmed: 26571352
Green R, Allen LH, Bjorke-Monsen AL, Brito A, Gueant JL, Miller JW, Molloy AM, Nexo E et al (2017) Vitamin B12 deficiency. Nat Rev Dis Primers 3:17040. https://doi.org/10.1038/nrdp.2017.40
doi: 10.1038/nrdp.2017.40
pubmed: 28660890
Griss T, Vincent EE, Egnatchik R, Chen J, Ma EH, Faubert B, Viollet B, DeBerardinis RJ et al (2015) Metformin antagonizes cancer cell proliferation by suppressing mitochondrial-dependent biosynthesis. PLoS Biol 13(12):e1002309. https://doi.org/10.1371/journal.pbio.1002309
doi: 10.1371/journal.pbio.1002309
pubmed: 26625127
pmcid: 4666657
Halliwell B (1999) Antioxidant defence mechanisms: from the beginning to the end (of the beginning). Free Radic Res 31(4):261–272. https://doi.org/10.1080/10715769900300841
doi: 10.1080/10715769900300841
pubmed: 10517532
Hao W, Chang CP, Tsao CC, Xu J (2010) Oligomycin-induced bioenergetic adaptation in cancer cells with heterogeneous bioenergetic organization. J Biol Chem 285(17):12647–12654. https://doi.org/10.1074/jbc.M109.084194
doi: 10.1074/jbc.M109.084194
pubmed: 20110356
pmcid: 2857128
Hatazawa Y, Senoo N, Tadaishi M, Ogawa Y, Ezaki O, Kamei Y, Miura S (2015) Metabolomic analysis of the skeletal muscle of mice overexpressing PGC-1alpha. PLoS ONE 10(6):e0129084. https://doi.org/10.1371/journal.pone.0129084
doi: 10.1371/journal.pone.0129084
pubmed: 26114427
pmcid: 4482640
Holecek M, Vodenicarovova M (2018) Effects of branched-chain amino acids on muscles under hyperammonemic conditions. J Physiol Biochem 74(4):523–530. https://doi.org/10.1007/s13105-018-0646-9
doi: 10.1007/s13105-018-0646-9
pubmed: 30058052
Hou Y, Lautrup S, Cordonnier S, Wang Y, Croteau DL, Zavala E, Zhang Y, Moritoh K et al (2018) NAD+ supplementation normalizes key Alzheimer’s features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency. Proc Natl Acad Sci 115(8):E1876. https://doi.org/10.1073/pnas.1718819115
doi: 10.1073/pnas.1718819115
pubmed: 29432159
Howarth KR, LeBlanc PJ, Heigenhauser GJ (1985) Gibala MJ (2004) Effect of endurance training on muscle TCA cycle metabolism during exercise in humans. J Appl Physiol 97(2):579–584. https://doi.org/10.1152/japplphysiol.01344.2003
doi: 10.1152/japplphysiol.01344.2003
Huang L, Wang C, Xu H, Peng G (2020) Targeting citrate as a novel therapeutic strategy in cancer treatment. Biochim Biophys Acta Rev Cancer 1873(1):188332. https://doi.org/10.1016/j.bbcan.2019.188332
doi: 10.1016/j.bbcan.2019.188332
pubmed: 31751601
Iacobazzi V, Infantino V (2014) Citrate—new functions for an old metabolite. Biol Chem 395(4):387–399. https://doi.org/10.1515/hsz-2013-0271
doi: 10.1515/hsz-2013-0271
pubmed: 24445237
Infantino V, Iacobazzi V, Palmieri F, Menga A (2013) ATP-citrate lyase is essential for macrophage inflammatory response. Biochem Biophys Res Commun 440(1):105–111. https://doi.org/10.1016/j.bbrc.2013.09.037
doi: 10.1016/j.bbrc.2013.09.037
pubmed: 24051091
Infantino V, Iacobazzi V, Menga A, Avantaggiati ML, Palmieri F (2014) A key role of the mitochondrial citrate carrier (SLC25A1) in TNFalpha- and IFNgamma-triggered inflammation. Biochim Biophys Acta 1839(11):1217–1225. https://doi.org/10.1016/j.bbagrm.2014.07.013
doi: 10.1016/j.bbagrm.2014.07.013
pubmed: 25072865
pmcid: 4346166
Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, Peters AL, Tsapas A et al (2015) Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 38(1):140–149. https://doi.org/10.2337/dc14-2441
doi: 10.2337/dc14-2441
pubmed: 25538310
Iovine B, Iannella ML, Nocella F, Pricolo MR, Bevilacqua MA (2012) Carnosine inhibits KRAS-mediated HCT116 proliferation by affecting ATP and ROS production. Cancer Lett 315(2):122–128. https://doi.org/10.1016/j.canlet.2011.07.021
doi: 10.1016/j.canlet.2011.07.021
pubmed: 22137144
Iovine B, Oliviero G, Garofalo M, Orefice M, Nocella F, Borbone N, Piccialli V, Centore R et al (2014) The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells. PLoS ONE 9(5):e96755. https://doi.org/10.1371/journal.pone.0096755
doi: 10.1371/journal.pone.0096755
pubmed: 24804733
pmcid: 4013086
Isidoro A, Casado E, Redondo A, Acebo P, Espinosa E, Alonso AM, Cejas P, Hardisson D et al (2005) Breast carcinomas fulfill the Warburg hypothesis and provide metabolic markers of cancer prognosis. Carcinogenesis 26(12):2095–2104. https://doi.org/10.1093/carcin/bgi188
doi: 10.1093/carcin/bgi188
pubmed: 16033770
Janssen JJE, Grefte S, Keijer J, de Boer VCJ (2019) Mito-nuclear communication by mitochondrial metabolites and its regulation by B-vitamins. Front Physiol 10:78. https://doi.org/10.3389/fphys.2019.00078
doi: 10.3389/fphys.2019.00078
pubmed: 30809153
pmcid: 6379835
Jha AK, Huang SC, Sergushichev A, Lampropoulou V, Ivanova Y, Loginicheva E, Chmielewski K, Stewart KM et al (2015) Network integration of parallel metabolic and transcriptional data reveals metabolic modules that regulate macrophage polarization. Immunity 42(3):419–430. https://doi.org/10.1016/j.immuni.2015.02.005
doi: 10.1016/j.immuni.2015.02.005
pubmed: 25786174
Jiang B (2017) Aerobic glycolysis and high level of lactate in cancer metabolism and microenvironment. Genes Dis 4(1):25–27. https://doi.org/10.1016/j.gendis.2017.02.003
doi: 10.1016/j.gendis.2017.02.003
pubmed: 30258905
pmcid: 6136593
Kamei Y, Hatazawa Y, Uchitomi R, Yoshimura R, Miura S (2020) Regulation of skeletal muscle function by amino acids. Nutrients 12(1):261. https://doi.org/10.3390/nu12010261
doi: 10.3390/nu12010261
pmcid: 7019684
Kang JO, Jones C, Brothwell B (1998) Toxicity associated with iron overload found in hemochromatosis: possible mechanism in a rat model. Clin Lab Sci 11(6):350
pubmed: 10345501
Kang R, Zeh HJ, Lotze MT, Tang D (2011) The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ 18(4):571–580. https://doi.org/10.1038/cdd.2010.191
doi: 10.1038/cdd.2010.191
pubmed: 21311563
pmcid: 3131912
Kimmelman AC, White E (2017) Autophagy and tumor metabolism. Cell Metab 25(5):1037–1043. https://doi.org/10.1016/j.cmet.2017.04.004
doi: 10.1016/j.cmet.2017.04.004
pubmed: 28467923
pmcid: 5604466
Klebanov GI, Teselkin YuO, Babenkova IV, Lyubitsky OB, Rebrova O, Boldyrev AA, Vladimirov YuA (1998) Effect of carnosine and its components on free-radical reactions. Membr Cell Biol 12(1):89–99
pubmed: 9829262
Korf H, du Plessis J, van Pelt J, De Groote S, Cassiman D, Verbeke L, Ghesquiere B, Fendt SM et al (2019) Inhibition of glutamine synthetase in monocytes from patients with acute-on-chronic liver failure resuscitates their antibacterial and inflammatory capacity. Gut 68(10):1872–1883. https://doi.org/10.1136/gutjnl-2018-316888
doi: 10.1136/gutjnl-2018-316888
pubmed: 30580251
Krebs HA, Johnson WA (1980) The role of citric acid in intermediate metabolism in animal tissues. FEBS Lett 117(Suppl):K1-10. https://doi.org/10.4159/harvard.9780674366701.c143
doi: 10.4159/harvard.9780674366701.c143
pubmed: 6998725
Kumar V, Gill KD (2009) Aluminium neurotoxicity: neurobehavioural and oxidative aspects. Arch Toxicol 83(11):965–978. https://doi.org/10.1007/s00204-009-0455-6
doi: 10.1007/s00204-009-0455-6
pubmed: 19568732
Kumar V, Gill KD (2014) Oxidative stress and mitochondrial dysfunction in aluminium neurotoxicity and its amelioration: a review. Neurotoxicology 41:154–166. https://doi.org/10.1016/j.neuro.2014.02.004
doi: 10.1016/j.neuro.2014.02.004
pubmed: 24560992
Lachowicz JI, Nurchi VM, Fanni D, Gerosa C, Peana M, Zoroddu MA (2014) Nutritional iron deficiency: the role of oral iron supplementation. Curr Med Chem 21(33):3775–3784. https://doi.org/10.2174/0929867321666140706143925
doi: 10.2174/0929867321666140706143925
pubmed: 25005180
Lautrup S, Sinclair DA, Mattson MP, Fang EF (2019) NAD(+) in brain aging and neurodegenerative disorders. Cell Metab 30(4):630–655. https://doi.org/10.1016/j.cmet.2019.09.001
doi: 10.1016/j.cmet.2019.09.001
pubmed: 31577933
pmcid: 6787556
Lee J, Park JR, Lee H, Jang S, Ryu SM, Kim H, Kim D, Jang A et al (2018) L-carnosine induces apoptosis/cell cycle arrest via suppression of NF-kappaB/STAT1 pathway in HCT116 colorectal cancer cells. Vitro Cell Dev Biol Anim 54(7):505–512. https://doi.org/10.1007/s11626-018-0264-4
doi: 10.1007/s11626-018-0264-4
Lemire J, Appanna VD (2011) Aluminum toxicity and astrocyte dysfunction: a metabolic link to neurological disorders. J Inorg Biochem 105(11):1513–1517. https://doi.org/10.1016/j.jinorgbio.2011.07.001
doi: 10.1016/j.jinorgbio.2011.07.001
pubmed: 22099161
Liberti MV, Locasale JW (2016) The Warburg effect: how does it benefit cancer cells? Trends Biochem Sci 41(3):211–218. https://doi.org/10.1016/j.tibs.2015.12.001
doi: 10.1016/j.tibs.2015.12.001
pubmed: 26778478
pmcid: 4783224
Lignitto L, LeBoeuf SE, Homer H, Jiang S, Askenazi M, Karakousi TR, Pass HI, Bhutkar AJ et al (2019) Nrf2 activation promotes lung cancer metastasis by inhibiting the degradation of Bach1. Cell 178(2):316–32918. https://doi.org/10.1016/j.cell.2019.06.003
doi: 10.1016/j.cell.2019.06.003
pubmed: 31257023
pmcid: 6625921
Linker RA, Lee DH, Ryan S, van Dam AM, Conrad R, Bista P, Zeng W, Hronowsky X et al (2011) Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 134(Pt 3):678–692. https://doi.org/10.1093/brain/awq386
doi: 10.1093/brain/awq386
pubmed: 21354971
Liu X, Romero IL, Litchfield LM, Lengyel E, Locasale JW (2016) Metformin targets central carbon metabolism and reveals mitochondrial requirements in human cancers. Cell Metab 24(5):728–739. https://doi.org/10.1016/j.cmet.2016.09.005
doi: 10.1016/j.cmet.2016.09.005
pubmed: 27746051
pmcid: 5889952
Lu M-C, Ji J-A, Jiang Z-Y, You Q-D (2016) The Keap1–Nrf2–ARE pathway as a potential preventive and therapeutic target: an update. Med Res Rev 36(5):924–963. https://doi.org/10.1002/med.21396
doi: 10.1002/med.21396
pubmed: 27192495
Lushchak OV, Piroddi M, Galli F, Lushchak VI (2014) Aconitase post-translational modification as a key in linkage between Krebs cycle, iron homeostasis, redox signaling, and metabolism of reactive oxygen species. Redox Rep 19(1):8–15. https://doi.org/10.1179/1351000213Y.0000000073
doi: 10.1179/1351000213Y.0000000073
pubmed: 24266943
Macedo LW, Cararo JH, Maravai SG, Goncalves CL, Oliveira GM, Kist LW, Guerra Martinez C, Kurtenbach E et al (2016) Acute carnosine administration increases respiratory chain complexes and citric acid cycle enzyme activities in cerebral cortex of young rats. Mol Neurobiol 53(8):5582–5590. https://doi.org/10.1007/s12035-015-9475-9
doi: 10.1007/s12035-015-9475-9
pubmed: 26476839
Mailloux RJ, Willmore WG (2014) S-glutathionylation reactions in mitochondrial function and disease. Front Cell Dev Biol 2:68. https://doi.org/10.3389/fcell.2014.00068
doi: 10.3389/fcell.2014.00068
pubmed: 25453035
pmcid: 4233936
Mailloux RJ, Hamel R, Appanna VD (2006) Aluminum toxicity elicits a dysfunctional TCA cycle and succinate accumulation in hepatocytes. J Biochem Mol Toxicol 20(4):198–208. https://doi.org/10.1002/jbt.20137
doi: 10.1002/jbt.20137
pubmed: 16906525
Mailloux RJ, Beriault R, Lemire J, Singh R, Chenier DR, Hamel RD, Appanna VD (2007) The tricarboxylic acid cycle, an ancient metabolic network with a novel twist. PLoS ONE 2(8):e690. https://doi.org/10.1371/journal.pone.0000690
doi: 10.1371/journal.pone.0000690
pubmed: 17668068
pmcid: 1930152
Mailloux RJ, McBride SL, Harper ME (2013) Unearthing the secrets of mitochondrial ROS and glutathione in bioenergetics. Trends Biochem Sci 38(12):592–602. https://doi.org/10.1016/j.tibs.2013.09.001
doi: 10.1016/j.tibs.2013.09.001
pubmed: 24120033
Mailloux RJ, Jin X, Willmore WG (2014) Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions. Redox Biol 2:123–139. https://doi.org/10.1016/j.redox.2013.12.011
doi: 10.1016/j.redox.2013.12.011
pubmed: 24455476
Mews P, Donahue G, Drake AM, Luczak V, Abel T, Berger SL (2017) Acetyl-CoA synthetase regulates histone acetylation and hippocampal memory. Nature 546(7658):381–386. https://doi.org/10.1038/nature22405
doi: 10.1038/nature22405
pubmed: 28562591
pmcid: 5505514
Nelson DL, Lehninger AL, Cox MM (2017) The citric acid cycle. Lehninger principles of biochemistry, 7th edn. Macmillan, New York, pp 619–624
Nurchi VM, Crisponi G, Lachowicz JI, Medici S, Peana M, Zoroddu MA (2016) Chemical features of in use and in progress chelators for iron overload. J Trace Elem Med Biol 38:10–18. https://doi.org/10.1016/j.jtemb.2016.05.010
doi: 10.1016/j.jtemb.2016.05.010
pubmed: 27365273
Nurchi VM, Cappai R, Chand K, Chaves S, Gano L, Crisponi G, Peana M, Zoroddu MA et al (2019) New strong extrafunctionalizable tris(3,4-HP) and bis(3,4-HP) metal sequestering agents: synthesis, solution and in vivo metal chelation. Dalton Trans 48(43):16167–16183. https://doi.org/10.1039/c9dt02905b
doi: 10.1039/c9dt02905b
pubmed: 31577287
Oexle H, Gnaiger E, Weiss G (1999) Iron-dependent changes in cellular energy metabolism: influence on citric acid cycle and oxidative phosphorylation. Biochim Biophys Acta 1413(3):99–107. https://doi.org/10.1016/s0005-2728(99)00088-2
doi: 10.1016/s0005-2728(99)00088-2
pubmed: 10556622
Oppermann H, Schnabel L, Meixensberger J, Gaunitz F (2016) Pyruvate attenuates the anti-neoplastic effect of carnosine independently from oxidative phosphorylation. Oncotarget 7(52):85848–85860. https://doi.org/10.18632/oncotarget.13039
doi: 10.18632/oncotarget.13039
pubmed: 27811375
pmcid: 5349879
Ott P, Clemmesen O, Larsen FS (2005) Cerebral metabolic disturbances in the brain during acute liver failure: from hyperammonemia to energy failure and proteolysis. Neurochem Int 47(1–2):13–18. https://doi.org/10.1016/j.neuint.2005.04.002
doi: 10.1016/j.neuint.2005.04.002
pubmed: 15921824
Owen OE, Kalhan SC, Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 277(34):30409–30412. https://doi.org/10.1074/jbc.R200006200
doi: 10.1074/jbc.R200006200
pubmed: 12087111
Palmieri F (2004) The mitochondrial transporter family (SLC25): physiological and pathological implications. Pflugers Arch 447(5):689–709. https://doi.org/10.1007/s00424-003-1099-7
doi: 10.1007/s00424-003-1099-7
pubmed: 14598172
Paumen MB, Ishida Y, Muramatsu M, Yamamoto M, Honjo T (1997) Inhibition of carnitine palmitoyltransferase I augments sphingolipid synthesis and palmitate-induced apoptosis. J Biol Chem 272(6):3324–3329. https://doi.org/10.1074/jbc.272.6.3324
doi: 10.1074/jbc.272.6.3324
pubmed: 9013572
Pietrocola F, Galluzzi L, Bravo-San Pedro JM, Madeo F, Kroemer G (2015) Acetyl coenzyme A: a central metabolite and second messenger. Cell Metab 21(6):805–821. https://doi.org/10.1016/j.cmet.2015.05.014
doi: 10.1016/j.cmet.2015.05.014
pubmed: 26039447
Prokopieva VD, Yarygina EG, Bokhan NA, Ivanova SA (2016) Use of carnosine for oxidative stress reduction in different pathologies. Oxid Med Cell Longev 2016:2939087–2939087. https://doi.org/10.1155/2016/2939087
doi: 10.1155/2016/2939087
pubmed: 26904160
pmcid: 4745351
Reid MA, Paik J, Locasale JW (2017) A missing link to vitamin B12 metabolism. Cell 171(4):736–737. https://doi.org/10.1016/j.cell.2017.10.030
doi: 10.1016/j.cell.2017.10.030
pubmed: 29100069
Rich PR (2003) The molecular machinery of Keilin’s respiratory chain. Biochem Soc Trans 31(Pt 6):1095–1105. https://doi.org/10.1042/bst0311095
doi: 10.1042/bst0311095
pubmed: 14641005
Roh JL, Jang H, Kim EH, Shin D (2017) Targeting of the glutathione, thioredoxin, and Nrf2 antioxidant systems in head and neck cancer. Antioxid Redox Signal 27(2):106–114. https://doi.org/10.1089/ars.2016.6841
doi: 10.1089/ars.2016.6841
pubmed: 27733046
Ross KL, Eisenstein RS (2002) Iron deficiency decreases mitochondrial aconitase abundance and citrate concentration without affecting tricarboxylic acid cycle capacity in rat liver. J Nutr 132(4):643–651. https://doi.org/10.1093/jn/132.4.643
doi: 10.1093/jn/132.4.643
pubmed: 11925455
Ruban A, Malina KC, Cooper I, Graubardt N, Babakin L, Jona G, Teichberg VI (2015) Combined treatment of an amyotrophic lateral sclerosis rat model with recombinant GOT1 and oxaloacetic acid: a novel neuroprotective treatment. Neurodegener Dis 15(4):233–242. https://doi.org/10.1159/000382034
doi: 10.1159/000382034
pubmed: 26113413
Ryan DG, Murphy MP, Frezza C, Prag HA, Chouchani ET, O’Neill LA, Mills EL (2019) Coupling Krebs cycle metabolites to signalling in immunity and cancer. Nat Metab 1:16–33. https://doi.org/10.1038/s42255-018-0014-7
doi: 10.1038/s42255-018-0014-7
pubmed: 31032474
pmcid: 6485344
Saggerson D (2008) Malonyl-CoA, a key signaling molecule in mammalian cells. Annu Rev Nutr 28:253–272. https://doi.org/10.1146/annurev.nutr.28.061807.155434
doi: 10.1146/annurev.nutr.28.061807.155434
pubmed: 18598135
Sajnani K, Islam F, Smith RA, Gopalan V, Lam AK (2017) Genetic alterations in Krebs cycle and its impact on cancer pathogenesis. Biochimie 135:164–172. https://doi.org/10.1016/j.biochi.2017.02.008
doi: 10.1016/j.biochi.2017.02.008
pubmed: 28219702
Sale C, Artioli GG, Gualano B, Saunders B, Hobson RM, Harris RC (2013) Carnosine: from exercise performance to health. Amino Acids 44(6):1477–1491. https://doi.org/10.1007/s00726-013-1476-2
doi: 10.1007/s00726-013-1476-2
pubmed: 23479117
Sawa K, Uematsu T, Korenaga Y, Hirasawa R, Kikuchi M, Murata K, Zhang J, Gai X et al (2017) Krebs cycle intermediates protective against oxidative stress by modulating the level of reactive oxygen species in neuronal HT22 cells. Antioxidants (Basel) 6(1):21. https://doi.org/10.3390/antiox6010021
doi: 10.3390/antiox6010021
Schranner D, Kastenmuller G, Schonfelder M, Romisch-Margl W, Wackerhage H (2020) Metabolite concentration changes in humans after a bout of exercise: a systematic review of exercise metabolomics studies. Sports Med Open 6(1):11. https://doi.org/10.1186/s40798-020-0238-4
doi: 10.1186/s40798-020-0238-4
pubmed: 32040782
pmcid: 7010904
Severina I, Bussygina O, Pyatakova N (2000) Carnosine as a regulator of soluble guanylate cyclase. Biochemistry (Moscow) 65(7):783–788
Shakoury-Elizeh M, Protchenko O, Berger A, Cox J, Gable K, Dunn TM, Prinz WA, Bard M et al (2010) Metabolic response to iron deficiency in Saccharomyces cerevisiae. J Biol Chem 285(19):14823–14833. https://doi.org/10.1074/jbc.M109.091710
doi: 10.1074/jbc.M109.091710
pubmed: 20231268
pmcid: 2863190
Shaw RJ, Lamia KA, Vasquez D, Koo SH, Bardeesy N, Depinho RA, Montminy M, Cantley LC (2005) The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310(5754):1642–1646. https://doi.org/10.1126/science.1120781
doi: 10.1126/science.1120781
pubmed: 3074427
pmcid: 3074427
Shen H, Campanello GC, Flicker D, Grabarek Z, Hu J, Luo C, Banerjee R, Mootha VK (2017) The human knockout gene CLYBL connects itaconate to vitamin B12. Cell 171(4):771-782e11. https://doi.org/10.1016/j.cell.2017.09.051
doi: 10.1016/j.cell.2017.09.051
pubmed: 29056341
pmcid: 5827971
Singh KK, Desouki MM, Franklin RB, Costello LC (2006) Mitochondrial aconitase and citrate metabolism in malignant and nonmalignant human prostate tissues. Mol Cancer 5:14. https://doi.org/10.1186/1476-4598-5-14
doi: 10.1186/1476-4598-5-14
pubmed: 16595004
pmcid: 1484490
Solomon LR (2007) Disorders of cobalamin (vitamin B12) metabolism: emerging concepts in pathophysiology, diagnosis and treatment. Blood Rev 21(3):113–130. https://doi.org/10.1016/j.blre.2006.05.001
doi: 10.1016/j.blre.2006.05.001
pubmed: 16814909
Starai VJ, Escalante-Semerena JC (2004) Acetyl-coenzyme A synthetase (AMP forming). Cell Mol Life Sci 61(16):2020–2030. https://doi.org/10.1007/s00018-004-3448-x
doi: 10.1007/s00018-004-3448-x
pubmed: 15316652
Stepien K, Ostrowski RP, Matyja E (2016) Hyperbaric oxygen as an adjunctive therapy in treatment of malignancies, including brain tumours. Med Oncol 33(9):101. https://doi.org/10.1007/s12032-016-0814-0
doi: 10.1007/s12032-016-0814-0
pubmed: 27485098
pmcid: 4971045
Strydom C, Robinson C, Pretorius E, Whitcutt J, Marx J, Bornman M (2006) The effect of selected metals on the central metabolic pathways in biology: a review. Water Sa 32(4):543–554
Swanson KV, Deng M, Ting JP (2019) The NLRP3 inflammasome: molecular activation and regulation to therapeutics. Nat Rev Immunol 19(8):477–489. https://doi.org/10.1038/s41577-019-0165-0
doi: 10.1038/s41577-019-0165-0
pubmed: 31036962
pmcid: 7807242
Tannahill GM, Curtis AM, Adamik J, Palsson-McDermott EM, McGettrick AF, Goel G, Frezza C, Bernard NJ et al (2013) Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature 496(7444):238–242. https://doi.org/10.1038/nature11986
doi: 10.1038/nature11986
pubmed: 23535595
pmcid: 4031686
Toyoshima S, Watanabe F, Saido H, Pezacka EH, Jacobsens DW, Miyatake K, Nakano Y (1996) Accumulation of methylmalonic acid caused by vitamin B12-deficiency disrupts normal cellular metabolism in rat liver. Br J Nutr 75(6):929–938. https://doi.org/10.1079/bjn19960198
doi: 10.1079/bjn19960198
pubmed: 8774237
Tretter L, Adam-Vizi V (2000) Inhibition of Krebs cycle enzymes by hydrogen peroxide: a key role of [alpha]-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress. J Neurosci 20(24):8972–8979
doi: 10.1523/JNEUROSCI.20-24-08972.2000
Vallee A, Vallee JN (2018) Warburg effect hypothesis in autism Spectrum disorders. Mol Brain 11(1):1. https://doi.org/10.1186/s13041-017-0343-6
doi: 10.1186/s13041-017-0343-6
pubmed: 29301575
pmcid: 5753567
Vander Heiden MG, Cantley LC, Thompson CB (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324(5930):1029–1033. https://doi.org/10.1126/science.1160809
doi: 10.1126/science.1160809
pubmed: 19460998
pmcid: 2849637
Vishnyakova K, Babizhayev M, Aliper A, Buzdin A, Kudryavzeva A, Yegorov Y (2014) Stimulation of cell proliferation by carnosine: Cell and transcriptome approaches. Mol Biol (Mosk) 48(5):718–726
doi: 10.1134/S0026893314050161
Wagenmakers A (1998) Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. Exerc Sport Sci Rev 26:287–314
doi: 10.1249/00003677-199800260-00013
Wahl D, Anderson RM, Le Couteur DG (2019) Anti-aging therapies, cognitive impairment and dementia. J Gerontol A Biol Sci Med Sci. https://doi.org/10.1093/gerona/glz135
doi: 10.1093/gerona/glz135
pmcid: 7749193
Wallace DC (2005) The mitochondrial genome in human adaptive radiation and disease: on the road to therapeutics and performance enhancement. Gene 354:169–180. https://doi.org/10.1016/j.gene.2005.05.001
doi: 10.1016/j.gene.2005.05.001
pubmed: 16024186
Waniewski RA, Martin DL (1998) Preferential utilization of acetate by astrocytes is attributable to transport. J Neurosci 18(14):5225–5233. https://doi.org/10.1523/jneurosci.18-14-05225.1998
doi: 10.1523/jneurosci.18-14-05225.1998
pubmed: 9651205
pmcid: 6793490
Wei YH, Lee HC (2002) Oxidative stress, mitochondrial DNA mutation, and impairment of antioxidant enzymes in aging. Exp Biol Med (Maywood) 227(9):671–682. https://doi.org/10.1177/153537020222700901
doi: 10.1177/153537020222700901
Williams NC, O’Neill LAJ (2018) A role for the Krebs cycle intermediate citrate in metabolic reprogramming in innate immunity and inflammation. Front Immunol 9:141. https://doi.org/10.3389/fimmu.2018.00141
doi: 10.3389/fimmu.2018.00141
pubmed: 29459863
pmcid: 5807345
Xue Y-N, Liu Y-N, Su J, Li J-L, Wu Y, Guo R, Yu B-B, Yan X-Y et al (2019) Zinc cooperates with p53 to inhibit the activity of mitochondrial aconitase through reactive oxygen species accumulation. Cancer Med 8(5):2462–2473. https://doi.org/10.1002/cam4.2130
doi: 10.1002/cam4.2130
pubmed: 30972978
pmcid: 6536939
Yalcin A, Telang S, Clem B, Chesney J (2009) Regulation of glucose metabolism by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases in cancer. Exp Mol Pathol 86(3):174–179. https://doi.org/10.1016/j.yexmp.2009.01.003
doi: 10.1016/j.yexmp.2009.01.003
pubmed: 19454274
Yang C, Ko B, Hensley CT, Jiang L, Wasti AT, Kim J, Sudderth J, Calvaruso MA et al (2014) Glutamine oxidation maintains the TCA cycle and cell survival during impaired mitochondrial pyruvate transport. Mol Cell 56(3):414–424. https://doi.org/10.1016/j.molcel.2014.09.025
doi: 10.1016/j.molcel.2014.09.025
pubmed: 25458842
pmcid: 4268166
Yudkoff M, Nelson D, Daikhin Y, Erecinska M (1994) Tricarboxylic acid cycle in rat brain synaptosomes. Fluxes and interactions with aspartate aminotransferase and malate/aspartate shuttle. J Biol Chem 269(44):27414–27420
doi: 10.1016/S0021-9258(18)47001-9
Zatta P, Lain E, Cagnolini C (2000) Effects of aluminum on activity of Krebs cycle enzymes and glutamate dehydrogenase in rat brain homogenate. Eur J Biochem 267(10):3049–3055. https://doi.org/10.1046/j.1432-1033.2000.01328.x
doi: 10.1046/j.1432-1033.2000.01328.x
pubmed: 10806405
Zhang D, Li J, Wang F, Hu J, Wang S, Sun Y (2014) 2-Deoxy-D-glucose targeting of glucose metabolism in cancer cells as a potential therapy. Cancer Lett 355(2):176–183. https://doi.org/10.1016/j.canlet.2014.09.003
doi: 10.1016/j.canlet.2014.09.003
pubmed: 25218591
Zhang D, Mably AJ, Walsh DM, Rowan MJ (2017) Peripheral interventions enhancing brain glutamate homeostasis relieve amyloid beta- and TNFalpha-mediated synaptic plasticity disruption in the rat hippocampus. Cereb Cortex 27(7):3724–3735. https://doi.org/10.1093/cercor/bhw193
doi: 10.1093/cercor/bhw193
pubmed: 27390019
Zhao J, Posa DK, Kumar V, Hoetker D, Kumar A, Ganesan S, Riggs DW, Bhatnagar A et al (2019) Carnosine protects cardiac myocytes against lipid peroxidation products. Amino Acids 51(1):123–138. https://doi.org/10.1007/s00726-018-2676-6
doi: 10.1007/s00726-018-2676-6
pubmed: 30449006
Zoroddu MA, Aaseth J, Crisponi G, Medici S, Peana M, Nurchi VM (2019) The essential metals for humans: a brief overview. J Inorg Biochem 195:120–129. https://doi.org/10.1016/j.jinorgbio.2019.03.013
doi: 10.1016/j.jinorgbio.2019.03.013
pubmed: 30939379
Zwingmann C, Leibfritz D, Hazell AS (2004) Brain energy metabolism in a sub-acute rat model of manganese neurotoxicity: an ex vivo nuclear magnetic resonance study using [1-13C]glucose. Neurotoxicology 25(4):573–587. https://doi.org/10.1016/j.neuro.2003.08.002
doi: 10.1016/j.neuro.2003.08.002
pubmed: 15183011