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Gene Review

Pcx  -  pyruvate carboxylase

Mus musculus

Synonyms: PCB, Pc, Pcb, Pyruvate carboxylase, mitochondrial, Pyruvic carboxylase
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Disease relevance of Pcx

  • No statistically significant increase in endometriotic lesion size was detected in animals treated with either PCB 126 or with the highest dose of 2,3,7,8-TCDD, possibly due to the effects of histologically observed ovarian toxicity [1].
  • Oral administration of a commercial PCB mixture to chickens caused a hepatic-type porphyria characterized by hepatic accumulation and urinary excretion of uroporphyrin [2].
  • The activation in vitro of the mutagens isolated from beef extract, when tested with Salmonella typhimurium strain TA1538, requires the presence of S9 fractions from livers of PCB- or 3-methylcholanthrene-induced rats [3].
  • Furthermore, the data suggest a potential involvement of an increased body burden of PCB compounds in the etiology of endometriosis in the rhesus [4].
  • The outbreak of yusho disease in Japan (which was caused by PCB-contaminated rice oil) and a similar episode of food poisoning in Taiwan (which was also related to PCB contamination) were discussed, particularly with reference to urinary porphyrin levels and clinical response [5].

Psychiatry related information on Pcx

  • Since DDT and PCB occur in milk, young animals may ingest these substances during the critical period of neonatal life; For this reason lactating mice were given injections of DDT or PCB, 50 mg/kg body weight, once a week for four weeks, the first injection being administered on the day of delivery [6].

High impact information on Pcx

  • In addition to the putative mitochondrial targeting signal, functional domains are readily identifiable in the sequence and are in the following order: biotin carboxylase-carboxyltransferase-biotin carboxyl-carrier protein, as proposed for yeast PC [7].
  • Adipose pyruvate carboxylase: amino acid sequence and domain structure deduced from cDNA sequencing [7].
  • The complete amino acid sequence of 3T3-L1 adipocyte pyruvate carboxylase (PC) [pyruvate:carbon-dioxide ligase (ADP-forming), EC] has been deduced from sequencing overlapping cDNA clones obtained from an adipocyte cDNA library constructed in the lambda Zap vector [7].
  • The biotinylated lysine of the encoded PC promoter (1178 amino acids with a calculated M(r) of apocarboxylase = 129,784) is located 35 residues from the COOH-terminal end and, as in most other biotin enzymes, is in the consensus sequence AMKM [7].
  • Induction of pyruvate carboxylase apoenzyme and holoenzyme in 3T3-L1 cells during differentiation [8].

Chemical compound and disease context of Pcx


Biological context of Pcx


Anatomical context of Pcx


Associations of Pcx with chemical compounds

  • And also the in vitro addition of various concentrations of enfenamic acid (0.25 to 3.0 mM) to the tissue extracts of liver inhibited the activities of important gluconeogenic enzymes such as pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK) and fructose 1,6-diphosphatase (FDPase) [17].
  • The effects of postnatal treatment with tumor-promoting agents, including 0.05% sodium barbital in the drinking water until death or a single dose of Aroclor 1254 (a mixture of polychlorinated biphenyls, PCB) given on Postnatal Day 8 or 56, were also examined [18].
  • This decrease in pyruvate carboxylase-mediated [14C] carbon fixation was associated with a reduction in fluorometrically determined [citrate] and [malate] [19].
  • This suggests that ETZ inhibition of lipogenesis involves an inhibitory effect on pyruvate carboxylase as opposed to acetyl CoA carboxylase, because the incorporation of glutamine into lipids does not involve pyruvate carboxylase [19].
  • The limited capacity of NAC to increase GSH synthesis was attributed to impaired glucose metabolism through PC [20].

Regulatory relationships of Pcx


Other interactions of Pcx


Analytical, diagnostic and therapeutic context of Pcx

  • Gel shift and chromatin immunoprecipitation assays demonstrated that endogenous PPARgamma binds to this functional PPAR-response element of the PC promoter [13].
  • Nine cDNA clones were isolated and three proved to be pyruvate carboxylase clones based on nucleotide sequencing and Northern blotting [16].
  • Molecular cloning of a cDNA for human pyruvate carboxylase. Structural relationship to other biotin-containing carboxylases and regulation of mRNA content in differentiating preadipocytes [16].
  • Detection and quantification of nanogram amounts of pyruvate carboxylase (apo and holo forms) in total tissue homogenates by immuno-blotting and by enzyme-linked immunosorbent assay are described [26].
  • In maternal and fetal liver, acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and beta-methylcrotonyl-CoA carboxylase abundances were determined by Western blotting; the content of mRNAs for most of these enzymes and holocarboxylase synthetase was determined by real-time RT-PCR [27].


  1. Promotion of endometriosis in mice by polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls. Johnson, K.L., Cummings, A.M., Birnbaum, L.S. Environ. Health Perspect. (1997) [Pubmed]
  2. Toxicity of polychlorinated biphenyl with special reference to porphyrin metabolism. Sano, S., Kawanishi, S., Seki, Y. Environ. Health Perspect. (1985) [Pubmed]
  3. Activation of the mutagens of beef extract in vitro and in vivo. Dolara, P., Barale, R., Mazzoli, S., Benetti, D. Mutat. Res. (1980) [Pubmed]
  4. The potential role of exposure to environmental toxicants in the pathophysiology of endometriosis. Rier, S.E. Ann. N. Y. Acad. Sci. (2002) [Pubmed]
  5. Mechanism of PCB-induced porphyria and yusho disease. Seki, Y., Kawanishi, S., Sano, S. Ann. N. Y. Acad. Sci. (1987) [Pubmed]
  6. Sexual functions of mice neonatally exposed to DDT or pcb. Kihlström, J.E., Lundberg, C., Orberg, J., Danielsson, P.O., Sydhoff, J. Environmental physiology & biochemistry. (1975) [Pubmed]
  7. Adipose pyruvate carboxylase: amino acid sequence and domain structure deduced from cDNA sequencing. Zhang, J., Xia, W.L., Brew, K., Ahmad, F. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  8. Induction of pyruvate carboxylase apoenzyme and holoenzyme in 3T3-L1 cells during differentiation. Freytag, S.O., Utter, M.F. Proc. Natl. Acad. Sci. U.S.A. (1980) [Pubmed]
  9. Detection of mutagenicity of procarbazine by the host-mediated assay with polychlorinated biphenyl (aroclor 1254) as enzyme inducer. Moriya, M., Watanabe, K., Ohta, T., Shirasu, Y. Mutat. Res. (1980) [Pubmed]
  10. Maternal and developmental toxicity of polychlorinated diphenyl ethers (PCDEs) in Swiss-Webster mice and Sprague-Dawley rats. Rosiak, K., Li, M.H., Degitz, S.J., Skalla, D.W., Chu, I., Francis, B.M. Toxicology (1997) [Pubmed]
  11. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induced alterations of pyruvate carboxylase levels and lactate dehydrogenase isozyme shifts in C57BL/6J male mice. Sparrow, B.R., Thompson, C.S., Ryu, B.W., Selevonchick, D.P., Schaup, H.W. J. Biochem. Toxicol. (1994) [Pubmed]
  12. Effect of ampicillin-induced alterations in murine intestinal microbiota on the survival and competition of environmentally released pseudomonads. George, S.E., Walsh, D.B., Stead, A.G., Claxton, L.D. Fundamental and applied toxicology : official journal of the Society of Toxicology. (1989) [Pubmed]
  13. The peroxisome proliferator-activated receptor-gamma regulates murine pyruvate carboxylase gene expression in vivo and in vitro. Jitrapakdee, S., Slawik, M., Medina-Gomez, G., Campbell, M., Wallace, J.C., Sethi, J.K., O'rahilly, S., Vidal-Puig, A.J. J. Biol. Chem. (2005) [Pubmed]
  14. Structural and promoter regions of the murine pyruvate carboxylase gene. Jitrapakdee, S., Petchamphai, N., Sunyakumthorn, P., Wallace, J.C., Boonsaeng, V. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  15. The role of glycolysis and gluconeogenesis in the cytoprotection of neuroblastoma cells against 1-methyl 4-phenylpyridinium ion toxicity. Mazzio, E., Soliman, K.F. Neurotoxicology (2003) [Pubmed]
  16. Molecular cloning of a cDNA for human pyruvate carboxylase. Structural relationship to other biotin-containing carboxylases and regulation of mRNA content in differentiating preadipocytes. Freytag, S.O., Collier, K.J. J. Biol. Chem. (1984) [Pubmed]
  17. The inhibitory effect of enfenamic acid (Tromaril) on hepatic gluconeogenesis in Swiss albino mice. Sreenath, T.L., Polasa, H. Biochem. Int. (1985) [Pubmed]
  18. Evaluation of the transplacental tumorigenicity of the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in mice. Anderson, L.M., Hecht, S.S., Dixon, D.E., Dove, L.F., Kovatch, R.M., Amin, S., Hoffmann, D., Rice, J.M. Cancer Res. (1989) [Pubmed]
  19. Differentiation-dependent expression of CA V and the role of carbonic anhydrase isozymes in pyruvate carboxylation in adipocytes. Hazen, S.A., Waheed, A., Sly, W.S., LaNoue, K.F., Lynch, C.J. FASEB J. (1996) [Pubmed]
  20. Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver. Zwingmann, C., Bilodeau, M. Hepatology (2006) [Pubmed]
  21. Prohibitin attenuates insulin-stimulated glucose and fatty acid oxidation in adipose tissue by inhibition of pyruvate carboxylase. Vessal, M., Mishra, S., Moulik, S., Murphy, L.J. FEBS J. (2006) [Pubmed]
  22. Immunofluorescent localization of acetyl CoA carboxylase, fatty acid synthetase and pyruvate carboxylase during the adipocyte conversion of 3T3 fibroblasts. Gratzner, H.G., Ahmad, P.M., Zegadlo, J., Ahmad, F. Cell Biol. Int. Rep. (1980) [Pubmed]
  23. Trafficking between glia and neurons of TCA cycle intermediates and related metabolites. Schousboe, A., Westergaard, N., Waagepetersen, H.S., Larsson, O.M., Bakken, I.J., Sonnewald, U. Glia (1997) [Pubmed]
  24. Krebs cycle enzymes from livers of old mice are differentially regulated by caloric restriction. Hagopian, K., Ramsey, J.J., Weindruch, R. Exp. Gerontol. (2004) [Pubmed]
  25. Caloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver. Hagopian, K., Ramsey, J.J., Weindruch, R. Exp. Gerontol. (2003) [Pubmed]
  26. Rat liver pyruvate carboxylase. Purification, detection and quantification of apo and holo forms by immuno-blotting and by an enzyme-linked immunosorbent assay. Ahmad, F., Ahmad, P.M., Mendez, A. Biochem. J. (1986) [Pubmed]
  27. Marginal maternal biotin deficiency in CD-1 mice reduces fetal mass of biotin-dependent carboxylases. Sealey, W.M., Stratton, S.L., Mock, D.M., Hansen, D.K. J. Nutr. (2005) [Pubmed]
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