The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
Chemical Compound Review

AC1L56DB     2-hydroxypropane-1,2,3- tricarboxylate;...

Synonyms: D02464, 50515-28-1, Iron-59 citrate, Ferric citrate (59 Fe)
This record was replaced with 311.
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of citric acid


High impact information on citric acid

  • The uptake of ferric citrate into the periplasmic space of fecA and tonB mutants via diffusion through the porin channels did not induce transcription of fec transport genes [2].
  • Here we demonstrate that ferric citrate uptake into the periplasmic space between the outer and the cytoplasmic membranes is not required for fec gene induction [2].
  • Point mutants in FecA displayed the constitutive expression of fec transport genes in the absence of ferric citrate but still required TonB, with the exception of one FecA mutant which showed a TonB-independent induction [2].
  • Rather, FecA and the TonB, ExbB and ExbD proteins are involved in induction of the fec transport genes independent of their role in ferric citrate transport across the outer membrane [2].
  • Functional analyses of these positions confirm their involvement in the mechanism that regulates transcriptional activation in response to ferric citrate binding at the cell surface [6].

Chemical compound and disease context of citric acid


Biological context of citric acid


Anatomical context of citric acid


Associations of citric acid with other chemical compounds


Gene context of citric acid

  • Total ferric citrate uptake by hepatocytes isolated from Hfe knockout mice (34.1 +/- 2.8 pmol Fe/mg protein/min) increased by 2-fold compared with control mice (17.8 +/- 2.7 pmol Fe/mg protein/min; P <.001; mean +/- SEM; n = 7) [15].
  • Mobility band shift of fecA promoter DNA caused by cell lysates required growth of cells in the presence of ferric citrate and expression of FecA, FecI and FecR [23].
  • We report that in vivo the chromosomally encoded FecI protein activates transcription of the fecA and fecB transport genes in response to ferric citrate and the FecR protein [24].
  • A mutation of FTR1 did not impair the use of these siderophores but did affect the uptake of ferrioxamines E and B, as well as of ferric citrate, indicating that their utilization was independent of Sit1p [25].
  • We conclude that transcription of the fec transport genes is regulated by FecI, which responds to ferric citrate via FecR. fecI and fecR co-transcription is inhibited by the iron-loaded Fur repressor, which then results in a low level of transcription of the fec transport genes [26].

Analytical, diagnostic and therapeutic context of citric acid

  • We observed a consistent sequence of activation changes in rat knee synovia following a single intravenous injection of sterile ferric citrate at a dosage sufficient to cause a transient saturation of transferrin [27].
  • Results of real-time PCR showed that A. actinomycetemcomitans JP2-12 exhibited significantly reduced expression of afuA (eightfold), fecBCDE (10-fold), and ftnAB (>50-fold), which encode a periplasmic ferric transport protein, a putative ferric citrate transporter, and ferritin, respectively [28].
  • In contrast, supplementation of the fish oil diets with ferric citrate, significantly (P less than 0.05) increased tumor lipid peroxidation product levels and decreased tumor volume [29].
  • Iron reductase activities for two substrates, ferripyochelin and ferric citrate, appear to be separate enzymes because of differences in heat stabilities, in locations in fractions of cell-free extracts, in reductant specificity, and in apparent sizes during gel filtration chromatography [30].
  • An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate [31].


  1. Hyperplastic foci in precancerous rat liver: light microscopic and electron microscopic study. Timme, A.H. J. Natl. Cancer Inst. (1978) [Pubmed]
  2. Signal transfer through three compartments: transcription initiation of the Escherichia coli ferric citrate transport system from the cell surface. Härle, C., Kim, I., Angerer, A., Braun, V. EMBO J. (1995) [Pubmed]
  3. Energy-coupled transport and signal transduction through the gram-negative outer membrane via TonB-ExbB-ExbD-dependent receptor proteins. Braun, V. FEMS Microbiol. Rev. (1995) [Pubmed]
  4. Cellular damage by ferric nitrilotriacetate and ferric citrate in V79 cells: interrelationship between lipid peroxidation, DNA strand breaks and sister chromatid exchanges. Hartwig, A., Klyszcz-Nasko, H., Schlepegrell, R., Beyersmann, D. Carcinogenesis (1993) [Pubmed]
  5. Characterization of a flavocytochrome that is induced during the anaerobic respiration of Fe3+ by Shewanella frigidimarina NCIMB400. Dobbin, P.S., Butt, J.N., Powell, A.K., Reid, G.A., Richardson, D.J. Biochem. J. (1999) [Pubmed]
  6. Signal transduction pathway of TonB-dependent transporters. Ferguson, A.D., Amezcua, C.A., Halabi, N.M., Chelliah, Y., Rosen, M.K., Ranganathan, R., Deisenhofer, J. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  7. Iron transport and its relation to heme biosynthesis in Rhodopseudomonas sphaeroides. Moody, M.D., Dailey, H.A. J. Bacteriol. (1985) [Pubmed]
  8. Mechanisms of ferric and ferrous iron uptake by Bifidobacterium bifidum var. pennsylvanicus. Bezkorovainy, A., Topouzian, N., Miller-Catchpole, R. Clinical physiology and biochemistry. (1986) [Pubmed]
  9. Role of cytochrome P-450 2E1 in ethanol-, carbon tetrachloride- and iron-dependent microsomal lipid peroxidation. Castillo, T., Koop, D.R., Kamimura, S., Triadafilopoulos, G., Tsukamoto, H. Hepatology (1992) [Pubmed]
  10. Contrasting effects of lactoferrin on human lymphocyte and monocyte natural killer activity and antibody-dependent cell-mediated cytotoxicity. Nishiya, K., Horwitz, D.A. J. Immunol. (1982) [Pubmed]
  11. New phosphate binding agents: ferric compounds. Hsu, C.H., Patel, S.R., Young, E.W. J. Am. Soc. Nephrol. (1999) [Pubmed]
  12. Cell cycle effects of iron depletion on T-47D human breast cancer cells. Reddel, R.R., Hedley, D.W., Sutherland, R.L. Exp. Cell Res. (1985) [Pubmed]
  13. Identification and characterization of a Streptococcus pyogenes operon involved in binding of hemoproteins and acquisition of iron. Bates, C.S., Montañez, G.E., Woods, C.R., Vincent, R.M., Eichenbaum, Z. Infect. Immun. (2003) [Pubmed]
  14. Transmembrane transcriptional control (surface signalling) of the Escherichia coli Fec type. Braun, V., Mahren, S. FEMS Microbiol. Rev. (2005) [Pubmed]
  15. Nontransferrin-bound iron uptake by hepatocytes is increased in the Hfe knockout mouse model of hereditary hemochromatosis. Chua, A.C., Olynyk, J.K., Leedman, P.J., Trinder, D. Blood (2004) [Pubmed]
  16. The H(+)-ATPase from reticulocyte endosomes reconstituted into liposomes acts as an iron transporter. Li, C.Y., Watkins, J.A., Glass, J. J. Biol. Chem. (1994) [Pubmed]
  17. Heavy chain ferritin enhances serine hydroxymethyltransferase expression and de novo thymidine biosynthesis. Oppenheim, E.W., Adelman, C., Liu, X., Stover, P.J. J. Biol. Chem. (2001) [Pubmed]
  18. Expression of the Haemophilus influenzae transferrin receptor is repressible by hemin but not elemental iron alone. Morton, D.J., Musser, J.M., Stull, T.L. Infect. Immun. (1993) [Pubmed]
  19. Macrophage permissiveness for Legionella pneumophila growth modulated by iron. Gebran, S.J., Newton, C., Yamamoto, Y., Widen, R., Klein, T.W., Friedman, H. Infect. Immun. (1994) [Pubmed]
  20. Ga-67 and Fe-59 distributions in mice. Sephton, R.G., Hodgson, G.S., De Abrew, S., Harris, A.W. J. Nucl. Med. (1978) [Pubmed]
  21. Effect of iron on renal tubular epithelial cells. Sponsel, H.T., Alfrey, A.C., Hammond, W.S., Durr, J.A., Ray, C., Anderson, R.J. Kidney Int. (1996) [Pubmed]
  22. Enhancement of estrogen-induced renal tumorigenesis in hamsters by dietary iron. Wyllie, S., Liehr, J.G. Carcinogenesis (1998) [Pubmed]
  23. Transcriptional regulation of ferric citrate transport in Escherichia coli K-12. Fecl belongs to a new subfamily of sigma 70-type factors that respond to extracytoplasmic stimuli. Angerer, A., Enz, S., Ochs, M., Braun, V. Mol. Microbiol. (1995) [Pubmed]
  24. Regulation of citrate-dependent iron transport of Escherichia coli: fecR is required for transcription activation by FecI. Ochs, M., Veitinger, S., Kim, I., Welz, D., Angerer, A., Braun, V. Mol. Microbiol. (1995) [Pubmed]
  25. The siderophore iron transporter of Candida albicans (Sit1p/Arn1p) mediates uptake of ferrichrome-type siderophores and is required for epithelial invasion. Heymann, P., Gerads, M., Schaller, M., Dromer, F., Winkelmann, G., Ernst, J.F. Infect. Immun. (2002) [Pubmed]
  26. Surface signaling in transcriptional regulation of the ferric citrate transport system of Escherichia coli: mutational analysis of the alternative sigma factor FecI supports its essential role in fec transport gene transcription. Ochs, M., Angerer, A., Enz, S., Braun, V. Mol. Gen. Genet. (1996) [Pubmed]
  27. Activation of rat synovium by iron. de Sousa, M., Dynesius-Trentham, R., Mota-Garcia, F., da Silva, M.T., Trentham, D.E. Arthritis Rheum. (1988) [Pubmed]
  28. luxS and arcB control aerobic growth of Actinobacillus actinomycetemcomitans under iron limitation. Fong, K.P., Gao, L., Demuth, D.R. Infect. Immun. (2003) [Pubmed]
  29. Effect of dietary fat on growth of MCF-7 and MDA-MB231 human breast carcinomas in athymic nude mice: relationship between carcinoma growth and lipid peroxidation product levels. Gonzalez, M.J., Schemmel, R.A., Gray, J.I., Dugan, L., Sheffield, L.G., Welsch, C.W. Carcinogenesis (1991) [Pubmed]
  30. Iron reductases from Pseudomonas aeruginosa. Cox, C.D. J. Bacteriol. (1980) [Pubmed]
  31. An open-label, crossover study of a new phosphate-binding agent in haemodialysis patients: ferric citrate. Yang, W.C., Yang, C.S., Hou, C.C., Wu, T.H., Young, E.W., Hsu, C.H. Nephrol. Dial. Transplant. (2002) [Pubmed]
WikiGenes - Universities