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Gene Review

Cs  -  citrate synthase

Mus musculus

Synonyms: 2610511A05Rik, 9030605P22Rik, BB234005, Cis, Citrate (Si)-synthase, ...
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Disease relevance of Cs

  • Mice with the mini-muscle phenotype had enlarged ventricles, with higher mass-specific citrate synthase activity and myoglobin concentration, which may account for their higher VO2 max in hypoxia [1].
  • Enzyme histochemistry, electron micrographs, and citrate synthase activity revealed a substantial increase in mitochondrial mass in skeletal muscle of the myopathy mice [2].
  • After five and nine weeks citrate synthase activity (a measure of mitochondrial respiratory chain activity), heart weight/body weight ratio, vascular reactivity, and protein expression of endothelial nitric oxide synthase (eNOS) were assessed [3].
  • Phylogenetic analysis of the 16S rRNA and the citrate synthase genes showed that the novel Bartonella species and a Bartonella isolate from a mouse captured on Martha's Vineyard, Massachusetts, were closely related to each other and secondarily related to Bartonella grahamii and Bartonella vinsonii [4].
  • Molecular analysis of the 17-kDa antigen gene and the citrate synthase gene has discriminated this bacterium from other typhus group and spotted fever group rickettsiae [5].

High impact information on Cs

  • Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells [6].
  • Specifically, activities expressed as a percentage of levels in normal animals were: citrate synthase, 135%; malate dehydrogenase, 130%; and glycogen phosphorylase, 170% [7].
  • These data, together with the significant increase in citrate synthase activity in heart, but not in soleus and gastrocnemius, suggest that distinct metabolic responses to altered mitochondrial outer membrane permeability occur in these different striated muscle types [8].
  • Cytochrome c was induced in the absence of any increase in citrate synthase activity or in subunit IV of the cytochrome c oxidase complex mRNA or protein, indicating that the enhanced respiratory rate did not require a general increase in mitochondrial biogenesis or respiratory chain expression [9].
  • Human cholesteryl ester transfer protein gene proximal promoter contains dietary cholesterol positive responsive elements and mediates expression in small intestine and periphery while predominant liver and spleen expression is controlled by 5'-distal sequences. Cis-acting sequences mapped in transgenic mice [10].

Biological context of Cs

  • Cis-elements (-933 to -641) upstream of the human M creatine kinase gene cap site contain an enhancer that confers developmental and tissue-specific expression to the chloramphenicol acetyltransferase gene in C2C12 myogenic cells transfected in culture [11].
  • RESULTS: Singularized mice showed a reduction of citrate synthase activity (p < 0.05), of endothelium-dependent vasorelaxation (to 65 +/- 5% of control levels; p < 0.001), and of eNOS protein expression (to 53 +/- 8% of control levels; p < 0.01) [3].
  • Direct assignment of citrate synthase (CS) gene to human chromosome 12 in man-mouse somatic cell hybrids [12].
  • In hearts of both 4- and 6-week-old Cn mice, genes involved in both FA and glucose metabolism and mitochondrial citrate synthase were down-regulated, reflecting an overall decline in metabolic gene expression, rather than a specific and preferential down-regulation of genes involved in FA uptake and metabolism [13].
  • The isolate was identified as B. quintana by a specific mouse polyclonal antibody and by determination of a partial gltA (citrate synthase-encoding) gene and 16S rRNA gene sequences [14].

Anatomical context of Cs

  • Here, we test the hypothesis that variation in VO2 max can be explained, in part, by hemoglobin concentration and Po2 necessary to obtain 50% O2 saturation of Hb (an estimate of Hb affinity for O2) of the blood as well as citrate synthase activity and myoglobin concentration of ventricles and gastrocnemius muscle [1].
  • All cell types expressed the enzyme citrate synthase at a high activity, the cerebellar granule neurons containing the enzyme at a higher activity than that found in the astrocytes from the two brain regions or the cortical neurons [15].
  • Striatum, cerebral cortex, and cerebellum contain similar activities of pyruvate dehydrogenase, citrate synthase, carnitine acetyltransferase, fatty acid synthetase, and acetyl-CoA hydrolase [16].
  • One month post-MI, the expression of several metabolic genes, i.e., acyl-CoA synthetase (-50%), muscle-type carnitine palmitoyl transferase 1 (-37%) and citrate synthase (-28%), was significantly reduced in the surviving myocardium [13].
  • In the purified secretory granule fraction, the insulin content was as high as 60% of the total protein (albumin standard) with arylsulfatase unchanged and no detectable citrate synthase activity [17].

Associations of Cs with chemical compounds

  • In other muscles, the enzyme-activity data suggest that both citrate synthase and the isocitrate dehydrogenase reactions are near-equilibrium [18].
  • These data indicate that the respective six- and threefold increases in the amounts of pyruvate dehydrogenase complex and citrate synthase found to occur in rat brain between birth and adulthood are mediated principally by translational and/or posttranslational mechanisms [19].
  • Accompanying this, the myocardial content of protein and the activities of lactate dehydrogenase, citrate synthase, and cytochrome c oxidase all decreased [20].
  • 1. The activities of citrate synthase and NAD+-linked and NADP+-linked isocitrate dehydrogenases were measured in nervous tissue from different animals in an attempt to provide more information about the citric acid cycle in this tissue [21].
  • There were lower concentrations of creatine phosphate (-41%), ATP (-22%), glycogen (-34%), and lactate (-31%) (P < 0.05) in H-FABP-null soleus muscles, but no differences in citrate synthase and beta-3-hydroxyacyl-CoA dehydrogenase activities or in the intramuscular triacylglycerol (TAG) depots [22].

Other interactions of Cs


Analytical, diagnostic and therapeutic context of Cs


  1. Maximal oxygen consumption in relation to subordinate traits in lines of house mice selectively bred for high voluntary wheel running. Rezende, E.L., Gomes, F.R., Malisch, J.L., Chappell, M.A., Garland, T. J. Appl. Physiol. (2006) [Pubmed]
  2. Increased mitochondrial mass in mitochondrial myopathy mice. Wredenberg, A., Wibom, R., Wilhelmsson, H., Graff, C., Wiener, H.H., Burden, S.J., Oldfors, A., Westerblad, H., Larsson, N.G. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  3. Physical inactivity causes endothelial dysfunction in healthy young mice. Suvorava, T., Lauer, N., Kojda, G. J. Am. Coll. Cardiol. (2004) [Pubmed]
  4. Cosegregation of a novel Bartonella species with Borrelia burgdorferi and Babesia microti in Peromyscus leucopus. Hofmeister, E.K., Kolbert, C.P., Abdulkarim, A.S., Magera, J.M., Hopkins, M.K., Uhl, J.R., Ambyaye, A., Telford, S.R., Cockerill, F.R., Persing, D.H. J. Infect. Dis. (1998) [Pubmed]
  5. Identification of a novel rickettsial infection in a patient diagnosed with murine typhus. Schriefer, M.E., Sacci, J.B., Dumler, J.S., Bullen, M.G., Azad, A.F. J. Clin. Microbiol. (1994) [Pubmed]
  6. Cis-acting elements conserved between mouse and pufferfish Otx2 genes govern the expression in mesencephalic neural crest cells. Kimura, C., Takeda, N., Suzuki, M., Oshimura, M., Aizawa, S., Matsuo, I. Development (1997) [Pubmed]
  7. "Increased" sensory stimulation leads to changes in energy-related enzymes in the brain. Dietrich, W.D., Durham, D., Lowry, O.H., Woolsey, T.A. J. Neurosci. (1982) [Pubmed]
  8. Altered mitochondrial sensitivity for ADP and maintenance of creatine-stimulated respiration in oxidative striated muscles from VDAC1-deficient mice. Anflous, K., Armstrong, D.D., Craigen, W.J. J. Biol. Chem. (2001) [Pubmed]
  9. Sequential serum-dependent activation of CREB and NRF-1 leads to enhanced mitochondrial respiration through the induction of cytochrome c. Herzig, R.P., Scacco, S., Scarpulla, R.C. J. Biol. Chem. (2000) [Pubmed]
  10. Human cholesteryl ester transfer protein gene proximal promoter contains dietary cholesterol positive responsive elements and mediates expression in small intestine and periphery while predominant liver and spleen expression is controlled by 5'-distal sequences. Cis-acting sequences mapped in transgenic mice. Oliveira, H.C., Chouinard, R.A., Agellon, L.B., Bruce, C., Ma, L., Walsh, A., Breslow, J.L., Tall, A.R. J. Biol. Chem. (1996) [Pubmed]
  11. The human M creatine kinase gene enhancer contains multiple functional interacting domains. Trask, R.V., Koster, J.C., Ritchie, M.E., Billadello, J.J. Nucleic Acids Res. (1992) [Pubmed]
  12. Direct assignment of citrate synthase (CS) gene to human chromosome 12 in man-mouse somatic cell hybrids. Wijnen, L.M., Grzeschik, K.H., Pearson, P.L., Meera Khan, P. Hum. Genet. (1977) [Pubmed]
  13. Specific and sustained down-regulation of genes involved in fatty acid metabolism is not a hallmark of progression to cardiac failure in mice. de Brouwer, K.F., Degens, H., Aartsen, W.M., Lindhout, M., Bitsch, N.J., Gilde, A.J., Willemsen, P.H., Janssen, B.J., van der Vusse, G.J., van Bilsen, M. J. Mol. Cell. Cardiol. (2006) [Pubmed]
  14. Bartonella (Rochalimaea) quintana infection in a seronegative hemodialyzed patient. Drancourt, M., Moal, V., Brunet, P., Dussol, B., Berland, Y., Raoult, D. J. Clin. Microbiol. (1996) [Pubmed]
  15. Uptake, release, and metabolism of citrate in neurons and astrocytes in primary cultures. Westergaard, N., Sonnewald, U., Unsgård, G., Peng, L., Hertz, L., Schousboe, A. J. Neurochem. (1994) [Pubmed]
  16. Regional and subcellular distribution of ATP-citrate lyase and other enzymes of acetyl-CoA metabolism in rat brain. Szutowicz, A., Lysiak, W. J. Neurochem. (1980) [Pubmed]
  17. Purification of mitochondria and secretory granules isolated from pancreatic beta cells using Percoll and Sephacryl S-1000 superfine. Andersson, T., Abrahamsson, H. Anal. Biochem. (1983) [Pubmed]
  18. Activities of citrate synthase and NAD+-linked and NADP+-linked isocitrate dehydrogenase in muscle from vertebrates and invertebrates. Alp, P.R., Newsholme, E.A., Zammit, V.A. Biochem. J. (1976) [Pubmed]
  19. The pyruvate dehydrogenase complex: cloning of the rat somatic E1 alpha subunit and its coordinate expression with the mRNAs for the E1 beta, E2, and E3 catalytic subunits in developing rat brain. Cullingford, T.E., Clark, J.B., Phillips, I.R. J. Neurochem. (1994) [Pubmed]
  20. Sequential metabolic alterations in the myocardium during influenza and tularemia in mice. Ilbäck, N.G., Friman, G., Beisel, W.R., Johnson, A.J. Infect. Immun. (1984) [Pubmed]
  21. Activities of citrate synthase, NAD+-linked and NADP+-linked isocitrate dehydrogenases, glutamate dehydrogenase, aspartate aminotransferase and alanine aminotransferase in nervous tissues from vertebrates and invertebrates. Sugden, P.H., Newsholme, E.A. Biochem. J. (1975) [Pubmed]
  22. A null mutation in H-FABP only partially inhibits skeletal muscle fatty acid metabolism. Binas, B., Han, X.X., Erol, E., Luiken, J.J., Glatz, J.F., Dyck, D.J., Motazavi, R., Adihetty, P.J., Hood, D.A., Bonen, A. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  23. The enzymes of acetyl-CoA metabolism in differentiating cholinergic (s-20) and noncholinergic (NIE-115) neuroblastoma cells. Szutowicz, A., Morrison, M.R., Srere, P.A. J. Neurochem. (1983) [Pubmed]
  24. Prolonged feeding of mice with conjugated linoleic acid increases hepatic fatty acid synthesis relative to oxidation. Javadi, M., Beynen, A.C., Hovenier, R., Lankhorst, A., Lemmens, A.G., Terpstra, A.H., Geelen, M.J. J. Nutr. Biochem. (2004) [Pubmed]
  25. Placenta growth factor is not required for exercise-induced angiogenesis. Gigante, B., Tarsitano, M., Cimini, V., De Falco, S., Persico, M.G. Angiogenesis (2004) [Pubmed]
  26. Endurance training increases skeletal muscle LKB1 and PGC-1alpha protein abundance: effects of time and intensity. Taylor, E.B., Lamb, J.D., Hurst, R.W., Chesser, D.G., Ellingson, W.J., Greenwood, L.J., Porter, B.B., Herway, S.T., Winder, W.W. Am. J. Physiol. Endocrinol. Metab. (2005) [Pubmed]
  27. Rats of the genus Rattus are reservoir hosts for pathogenic Bartonella species: an Old World origin for a New World disease? Ellis, B.A., Regnery, R.L., Beati, L., Bacellar, F., Rood, M., Glass, G.G., Marston, E., Ksiazek, T.G., Jones, D., Childs, J.E. J. Infect. Dis. (1999) [Pubmed]
  28. Distribution, diversity, and host specificity of Bartonella in rodents from the Southeastern United States. Kosoy, M.Y., Regnery, R.L., Tzianabos, T., Marston, E.L., Jones, D.C., Green, D., Maupin, G.O., Olson, J.G., Childs, J.E. Am. J. Trop. Med. Hyg. (1997) [Pubmed]
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