Experts and Doctors on citric acid cycle in United States


Locale: United States
Topic: citric acid cycle

Top Publications

  1. Anderson E, Kypson A, Rodriguez E, Anderson C, Lehr E, Neufer P. Substrate-specific derangements in mitochondrial metabolism and redox balance in the atrium of the type 2 diabetic human heart. J Am Coll Cardiol. 2009;54:1891-8 pubmed publisher
  2. Sadler N, Angel T, LEWIS M, Pederson L, Chauvigne Hines L, Wiedner S, et al. Activity-based protein profiling reveals mitochondrial oxidative enzyme impairment and restoration in diet-induced obese mice. PLoS ONE. 2012;7:e47996 pubmed publisher
  3. Kruse A, Fattah Hosseini S, Saha S, Johnson R, Warwick E, Sturgeon K, et al. Combining 'omics and microscopy to visualize interactions between the Asian citrus psyllid vector and the Huanglongbing pathogen Candidatus Liberibacter asiaticus in the insect gut. PLoS ONE. 2017;12:e0179531 pubmed publisher
    ..Our study provides a snapshot of how the psyllid gut copes with CLas exposure and provides information on pathways and proteins for targeted disruption of CLas-vector interactions at the gut interface. ..
  4. MacDonald M, Brown L, Longacre M, Stoker S, Kendrick M, Hasan N. Knockdown of both mitochondrial isocitrate dehydrogenase enzymes in pancreatic beta cells inhibits insulin secretion. Biochim Biophys Acta. 2013;1830:5104-11 pubmed publisher
    ..As almost all mammalian cells possess substantial amounts of all three IDH enzymes, the biological principles suggested by these results are probably extrapolatable to many tissues. ..
  5. Toth M, MacCoss M, Poehlman E, Matthews D. Recovery of (13)CO(2) from infused [1-(13)C]leucine and [1,2-(13)C(2)]leucine in healthy humans. Am J Physiol Endocrinol Metab. 2001;281:E233-41 pubmed
  6. Xu X, Hu J, McGrath B, Cavener D. GCN2 regulates the CCAAT enhancer binding protein beta and hepatic gluconeogenesis. Am J Physiol Endocrinol Metab. 2013;305:E1007-17 pubmed publisher
    ..Our study demonstrates that GCN2 is important in maintaining GNG in the liver, which is likely to be mediated through regulation of C/EBP?. ..
  7. Frizzell N, Thomas S, Carson J, Baynes J. Mitochondrial stress causes increased succination of proteins in adipocytes in response to glucotoxicity. Biochem J. 2012;445:247-54 pubmed publisher
    ..We propose that increased succination of proteins is an early marker of glucotoxicity and mitochondrial stress in adipose tissue in diabetes. ..
  8. Lemons J, Feng X, Bennett B, Legesse Miller A, Johnson E, Raitman I, et al. Quiescent fibroblasts exhibit high metabolic activity. PLoS Biol. 2010;8:e1000514 pubmed publisher
    ..Quiescent fibroblasts, relieved of the biosynthetic requirements associated with generating progeny, direct their metabolic activity to preservation of self integrity and alternative functions beneficial to the organism as a whole. ..
  9. Brunengraber H, Roe C. Anaplerotic molecules: current and future. J Inherit Metab Dis. 2006;29:327-31 pubmed
    ..The properties of the main anaplerotic substrates are reviewed from the point of view of potential clinical applications to the treatment of some inherited and acquired conditions. ..

More Information


  1. Choi J, Antoniewicz M. Tandem mass spectrometry: a novel approach for metabolic flux analysis. Metab Eng. 2011;13:225-33 pubmed publisher
    ..Application of tandem MS increased the observability of the models and improved the precision of estimated fluxes by 2- to 5-fold compared to traditional MS analysis. ..
  2. Oliver M, Guo L, Alexander D, Ryals J, Wone B, Cushman J. A sister group contrast using untargeted global metabolomic analysis delineates the biochemical regulation underlying desiccation tolerance in Sporobolus stapfianus. Plant Cell. 2011;23:1231-48 pubmed publisher
    ..Collectively, the metabolic profiles obtained uncovered a cascade of biochemical regulation strategies critical to the survival of S. stapfianus under desiccation. ..
  3. Yang L, Kasumov T, Kombu R, Zhu S, Cendrowski A, David F, et al. Metabolomic and mass isotopomer analysis of liver gluconeogenesis and citric acid cycle: II. Heterogeneity of metabolite labeling pattern. J Biol Chem. 2008;283:21988-96 pubmed publisher
    ..Our data have implications for the use of labeling patterns for the calculation of metabolic rates or fractional syntheses in liver, as well as for modeling liver intermediary metabolism. ..
  4. Ludwig T, Squirrell J, Palmenberg A, Bavister B. Relationship between development, metabolism, and mitochondrial organization in 2-cell hamster embryos in the presence of low levels of phosphate. Biol Reprod. 2001;65:1648-54 pubmed
    ..Additionally, although 2-cell embryos can tolerate some structural disruption without concomitant, detrimental effects on development or metabolic activity, metabolic disturbance is associated with decreased developmental competence. ..
  5. Ahn W, Antoniewicz M. Parallel labeling experiments with [1,2-(13)C]glucose and [U-(13)C]glutamine provide new insights into CHO cell metabolism. Metab Eng. 2013;15:34-47 pubmed publisher
    ..Follow-up experiments with [U-(13)C]glucose confirmed that additional metabolites were accumulating in the medium that became M+3 and M+6 labeled. ..
  6. Ahn W, Antoniewicz M. Metabolic flux analysis of CHO cells at growth and non-growth phases using isotopic tracers and mass spectrometry. Metab Eng. 2011;13:598-609 pubmed publisher
    ..The results presented here provide a solid foundation for future studies of CHO cell metabolism for applications such as cell line development and medium optimization for high-titer production of recombinant proteins. ..
  7. Ledee D, Portman M, Kajimoto M, Isern N, Olson A. Thyroid hormone reverses aging-induced myocardial fatty acid oxidation defects and improves the response to acutely increased afterload. PLoS ONE. 2013;8:e65532 pubmed publisher
    ..Thyroid hormone supplementation in aged mice significantly improves cardiac function potentially through restoration of fatty acid oxidation. ..
  8. Bonda D, Wang X, Perry G, Smith M, Zhu X. Mitochondrial dynamics in Alzheimer's disease: opportunities for future treatment strategies. Drugs Aging. 2010;27:181-92 pubmed publisher
    ..e. mitochondrial protection) that has the potential to significantly deter AD progression if adequately developed. Current treatment strategies under investigation are described in this review. ..
  9. Sheikh Ali M, Sultan S, Alamir A, Haas M, Mooradian A. Hyperglycemia-induced endoplasmic reticulum stress in endothelial cells. Nutrition. 2010;26:1146-50 pubmed publisher
    ..Although the mitochondria are the site of signals generated by dextrose to initiate oxidative stress, the dextrose-induced ER stress, unlike SO generation, does not require pyruvate oxidation in the mitochondria. ..
  10. Chan L, Chen Z, Braas D, Lee J, Xiao G, Geng H, et al. Metabolic gatekeeper function of B-lymphoid transcription factors. Nature. 2017;542:479-483 pubmed publisher
    ..Thus, B-lymphoid transcription factors function as metabolic gatekeepers by limiting the amount of cellular ATP to levels that are insufficient for malignant transformation. ..
  11. Du J, Rountree A, Cleghorn W, Contreras L, Lindsay K, Sadilek M, et al. Phototransduction Influences Metabolic Flux and Nucleotide Metabolism in Mouse Retina. J Biol Chem. 2016;291:4698-710 pubmed publisher
    ..In addition, a comprehensive analysis of the retinal metabolome showed that phototransduction also influences steady-state concentrations of 5'-GMP, ribose-5-phosphate, ketone bodies, and purines. ..
  12. Cordova L, Antoniewicz M. (13)C metabolic flux analysis of the extremely thermophilic, fast growing, xylose-utilizing Geobacillus strain LC300. Metab Eng. 2016;33:148-57 pubmed publisher
    ..No transhydrogenase activity was detected. Results from this work provide a solid foundation for future studies of this strain and its metabolic engineering and biotechnological applications. ..
  13. Yang L, Kombu R, Kasumov T, Zhu S, Cendrowski A, David F, et al. Metabolomic and mass isotopomer analysis of liver gluconeogenesis and citric acid cycle. I. Interrelation between gluconeogenesis and cataplerosis; formation of methoxamates from aminooxyacetate and ketoacids. J Biol Chem. 2008;283:21978-87 pubmed publisher
    ..These adducts may exert metabolic effects unrelated to their effect on gluconeogenesis. ..
  14. Barding G, Beni S, Fukao T, Bailey Serres J, Larive C. Comparison of GC-MS and NMR for metabolite profiling of rice subjected to submergence stress. J Proteome Res. 2013;12:898-909 pubmed publisher
    ..The combined metabolic information provided by (1)H NMR and GC-MS was essential for understanding the complex biochemical and molecular response of rice plants to submergence. ..
  15. Green L, Li Y, Emerich D, Bergersen F, Day D. Catabolism of alpha-ketoglutarate by a sucA mutant of Bradyrhizobium japonicum: evidence for an alternative tricarboxylic acid cycle. J Bacteriol. 2000;182:2838-44 pubmed
  16. Chalhoub E, Hanson R, Belovich J. A computer model of gluconeogenesis and lipid metabolism in the perfused liver. Am J Physiol Endocrinol Metab. 2007;293:E1676-86 pubmed
    ..5-4 min) and the dynamic behavior of substrate and product fluxes. It is expected that this model will be a useful tool for analyzing the complex relationships between carbohydrate and fat metabolism. ..
  17. Munger J, Bajad S, Coller H, Shenk T, Rabinowitz J. Dynamics of the cellular metabolome during human cytomegalovirus infection. PLoS Pathog. 2006;2:e132 pubmed
  18. Sharma N, Okere I, Brunengraber D, McElfresh T, King K, Sterk J, et al. Regulation of pyruvate dehydrogenase activity and citric acid cycle intermediates during high cardiac power generation. J Physiol. 2005;562:593-603 pubmed
  19. Marin Garcia J, Goldenthal M, Moe G. Selective endothelin receptor blockade reverses mitochondrial dysfunction in canine heart failure. J Card Fail. 2002;8:326-32 pubmed
    ..Improvement of mitochondrial function may be a novel mechanism mediating the beneficial effect of ET(A) receptor blockade in CHF. ..
  20. Traaseth N, Elfering S, Solien J, Haynes V, Giulivi C. Role of calcium signaling in the activation of mitochondrial nitric oxide synthase and citric acid cycle. Biochim Biophys Acta. 2004;1658:64-71 pubmed
    ..This would ensue in changes in the NADH/NAD and ATP/ADP ratios, which would influence the rate of the cycle and the oxygen diffusion. ..
  21. Simpson N, Khokhlova N, Oca Cossio J, Constantinidis I. Insights into the role of anaplerosis in insulin secretion: A 13C NMR study. Diabetologia. 2006;49:1338-48 pubmed
    ..On the basis of our findings, a strong correlation may exist between stimulated insulin secretion and non-pyruvate carboxylase anaplerosis for the four cell lines examined in this study. ..
  22. Okere I, McElfresh T, Brunengraber D, Martini W, Sterk J, Huang H, et al. Differential effects of heptanoate and hexanoate on myocardial citric acid cycle intermediates following ischemia-reperfusion. J Appl Physiol (1985). 2006;100:76-82 pubmed
    ..This suggests that reduced anaplerosis and CAC dysfunction do not play a major role in contractile and metabolic derangements observed with a 60% decrease in coronary flow followed by reperfusion. ..
  23. Kimmich G, Roussie J, Randles J. Aspartate aminotransferase isotope exchange reactions: implications for glutamate/glutamine shuttle hypothesis. Am J Physiol Cell Physiol. 2002;282:C1404-13 pubmed
    ..AAT isotope exchange is discussed in the context of the glutamate/glutamine shuttle hypothesis for astrocyte/neuron carbon cycling. ..
  24. Crown S, Indurthi D, Ahn W, Choi J, Papoutsakis E, Antoniewicz M. Resolving the TCA cycle and pentose-phosphate pathway of Clostridium acetobutylicum ATCC 824: Isotopomer analysis, in vitro activities and expression analysis. Biotechnol J. 2011;6:300-5 pubmed publisher
  25. Anderson A, Roberts P, Frisard M, McMillan R, Brown T, Lawless M, et al. Metabolic changes during ovarian cancer progression as targets for sphingosine treatment. Exp Cell Res. 2013;319:1431-42 pubmed publisher
  26. Sykes S, Hajduk S. Dual functions of ?-ketoglutarate dehydrogenase E2 in the Krebs cycle and mitochondrial DNA inheritance in Trypanosoma brucei. Eukaryot Cell. 2013;12:78-90 pubmed publisher
    ..These results indicate that ?-KDE2 is bifunctional, both as a metabolic enzyme and as a mitochondrial inheritance factor necessary for the distribution of kDNA networks to daughter cells at cytokinesis. ..
  27. Green L, Waters J, Ko S, Emerich D. Comparative analysis of the Bradyrhizobium japonicum sucA region. Can J Microbiol. 2003;49:237-43 pubmed
    ..Primer extension indicated that the sucA operon and mdh were transcribed from typical housekeeping promoters. ..
  28. Grassian A, Parker S, Davidson S, Divakaruni A, Green C, Zhang X, et al. IDH1 mutations alter citric acid cycle metabolism and increase dependence on oxidative mitochondrial metabolism. Cancer Res. 2014;74:3317-31 pubmed publisher
    ..Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation. ..
  29. Nulton Persson A, Szweda L, Sadek H. Inhibition of cardiac mitochondrial respiration by salicylic acid and acetylsalicylate. J Cardiovasc Pharmacol. 2004;44:591-5 pubmed
    ..The effects of salicylic acid and acetylsalicylate on cardiac mitochondrial function may contribute to the known cardioprotective effects of therapeutic doses of aspirin, as well as to the toxicity associated with salicylate overdose. ..
  30. Goffredi S, Jones W, Erhlich H, Springer A, Vrijenhoek R. Epibiotic bacteria associated with the recently discovered Yeti crab, Kiwa hirsuta. Environ Microbiol. 2008;10:2623-34 pubmed publisher
    ..Consequently, the potential for carbon fixation and cycling of reduced and oxidized sulfur appear to exist in the dense microflora that grows on the crab's setae...
  31. Horswill A, Escalante Semerena J. In vitro conversion of propionate to pyruvate by Salmonella enterica enzymes: 2-methylcitrate dehydratase (PrpD) and aconitase Enzymes catalyze the conversion of 2-methylcitrate to 2-methylisocitrate. Biochemistry. 2001;40:4703-13 pubmed
    ..The phenotype of this double mutant indicates that the aconitase enzymes are required for the 2-methylcitric acid cycle during propionate catabolism. ..
  32. Wilson K, Han Y, Zhang M, Hess J, Chapman K, Cline G, et al. Inter-relations between 3-hydroxypropionate and propionate metabolism in rat liver: relevance to disorders of propionyl-CoA metabolism. Am J Physiol Endocrinol Metab. 2017;313:E413-E428 pubmed publisher
    ..e., millimolar, concentrations of labeled propionate used to trace the intermediary metabolism, in particular, inhibition of CAC flux and major decreases in the [ATP]/[ADP] and [ATP]/[AMP] ratios. ..
  33. Ragavan M, Kirpich A, Fu X, Burgess S, McIntyre L, Merritt M. A comprehensive analysis of myocardial substrate preference emphasizes the need for a synchronized fluxomic/metabolomic research design. Am J Physiol Heart Circ Physiol. 2017;312:H1215-H1223 pubmed publisher
    ..This observation leads to a key observation regarding mass balance in the TCA cycle; flux through a portion of the cycle can be drastically elevated without changing the O2 consumption. ..
  34. Stacpoole P. Therapeutic Targeting of the Pyruvate Dehydrogenase Complex/Pyruvate Dehydrogenase Kinase (PDC/PDK) Axis in Cancer. J Natl Cancer Inst. 2017;109: pubmed publisher
  35. Piroli G, Manuel A, Clapper A, Walla M, Baatz J, Palmiter R, et al. Succination is Increased on Select Proteins in the Brainstem of the NADH dehydrogenase (ubiquinone) Fe-S protein 4 (Ndufs4) Knockout Mouse, a Model of Leigh Syndrome. Mol Cell Proteomics. 2016;15:445-61 pubmed publisher
    ..These data suggest that fumarate is a novel biochemical link that may contribute to the progression of the neuropathology in this mitochondrial disease model. ..
  36. Dexter J, Gunawardena J. Dimerization and bifunctionality confer robustness to the isocitrate dehydrogenase regulatory system in Escherichia coli. J Biol Chem. 2013;288:5770-8 pubmed publisher
    ..Our work unifies much of the known biochemistry of the IDH regulatory system into a single quantitative framework and highlights the importance of constructing biochemically realistic models in systems biology...
  37. Priddy C, Kajimoto M, Ledee D, Bouchard B, Isern N, Olson A, et al. Myocardial oxidative metabolism and protein synthesis during mechanical circulatory support by extracorporeal membrane oxygenation. Am J Physiol Heart Circ Physiol. 2013;304:H406-14 pubmed publisher
  38. Chistoserdova L, Chen S, Lapidus A, Lidstrom M. Methylotrophy in Methylobacterium extorquens AM1 from a genomic point of view. J Bacteriol. 2003;185:2980-7 pubmed
  39. Wolfe A. The acetate switch. Microbiol Mol Biol Rev. 2005;69:12-50 pubmed
    ..Next, the way in which cells regulate AMP-ACS activity through reversible acetylation is described. Finally, the "acetate switch" as it exists in selected eubacteria, archaea, and eukaryotes, including humans, is described. ..
  40. Mason K, Stofan D. Endotoxin challenge reduces aconitase activity in myocardial tissue. Arch Biochem Biophys. 2008;469:151-6 pubmed
    ..We conclude that decreased activity of aconitase contributes to the endotoxin-stimulated reduction in mitochondrial respiration. ..
  41. Manolukas J, Barile M, Chandler D, Pollack J. Presence of anaplerotic reactions and transamination, and the absence of the tricarboxylic acid cycle in mollicutes. J Gen Microbiol. 1988;134:791-800 pubmed
    ..CO2 fixation appears obligatory in the Acholeplasma species and either CO2 fixation or malate synthesis appears obligatory in the Mycoplasma species...
  42. Peters J. Flipping a citrate switch on liver cancer cells. J Biol Chem. 2017;292:13902-13903 pubmed publisher
  43. Eng C, Kiuru M, Fernandez M, Aaltonen L. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat Rev Cancer. 2003;3:193-202 pubmed
    ..Understanding this link between inherited cancer syndromes and neurological disease could provide further insights into the mechanisms by which mitochondrial deficiencies lead to tumour development. ..
  44. Kumar M, Rowley S, Fulton R, Dinday M, Baraban S, Patel M. Altered Glycolysis and Mitochondrial Respiration in a Zebrafish Model of Dravet Syndrome. Eneuro. 2016;3: pubmed publisher
    ..Our findings in scn1Lab mutant zebrafish suggest that glucose and mitochondrial hypometabolism contribute to the pathophysiology of DS. ..
  45. MacDonald M, Longacre M, Stoker S, Brown L, Hasan N, Kendrick M. Acetoacetate and beta-hydroxybutyrate in combination with other metabolites release insulin from INS-1 cells and provide clues about pathways in insulin secretion. Am J Physiol Cell Physiol. 2008;294:C442-50 pubmed
    ..The results suggest that, besides citrate, some of the products of anaplerosis are SC-CoAs, which may be precursors of molecules involved in insulin secretion. ..
  46. Andrews M, Russeth K, Drewes L, Henry P. Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor. Am J Physiol Regul Integr Comp Physiol. 2009;296:R383-93 pubmed publisher
    ..This finding suggests that fuel selection is controlled at the level of individual metabolic pathways and that seasonally induced adaptive mechanisms give rise to the strategic utilization of BHB during hibernation...
  47. Frizzell N, Rajesh M, Jepson M, Nagai R, Carson J, Thorpe S, et al. Succination of thiol groups in adipose tissue proteins in diabetes: succination inhibits polymerization and secretion of adiponectin. J Biol Chem. 2009;284:25772-81 pubmed publisher
  48. Amador Noguez D, Feng X, Fan J, Roquet N, Rabitz H, Rabinowitz J. Systems-level metabolic flux profiling elucidates a complete, bifurcated tricarboxylic acid cycle in Clostridium acetobutylicum. J Bacteriol. 2010;192:4452-61 pubmed publisher
  49. Wang Q, Nomura C. Monitoring differences in gene expression levels and polyhydroxyalkanoate (PHA) production in Pseudomonas putida KT2440 grown on different carbon sources. J Biosci Bioeng. 2010;110:653-9 pubmed publisher
    ..This information will be invaluable to understand how genes are regulated and construct transgenic strains to utilize carbon sources more efficiently and better produce PHAs. ..
  50. Vastag L, Koyuncu E, Grady S, Shenk T, Rabinowitz J. Divergent effects of human cytomegalovirus and herpes simplex virus-1 on cellular metabolism. PLoS Pathog. 2011;7:e1002124 pubmed publisher
    ..Although our results confirm that this is a robust target for HSV-1, therapeutic interventions at other points in metabolism might prove more effective for treatment of HCMV...
  51. Yuan Y, Kadiyala C, Ching T, Hakimi P, Saha S, Xu H, et al. Enhanced energy metabolism contributes to the extended life span of calorie-restricted Caenorhabditis elegans. J Biol Chem. 2012;287:31414-26 pubmed publisher
    ..We conclude that an increase, not a decrease in fuel consumption, via an accelerated oxidation of fuels in the TCA cycle is involved in life span regulation; this mechanism may be conserved across phylogeny. ..
  52. Minato Y, Fassio S, HASE C. Malonate inhibits virulence gene expression in Vibrio cholerae. PLoS ONE. 2013;8:e63336 pubmed publisher
    ..cholerae growth. All together, these results suggest that metabolizing malonate as a nutrient source negatively affects virulence gene expression in V. cholerae. ..