Protein Information

Name pyruvate carboxylase
Synonyms PC; PCB; Pyruvate carboxylase; Pyruvic carboxylase; Pyruvate carboxylases; Pyruvic carboxylases; Carboxylase, pyruvate

Compound Information

Name TCA
CAS 2,2,2-trichloroacetic acid

Reference List

PubMed Abstract RScore(About this table)
12573011 Elias CB, Carpentier E, Durocher Y, Bisson L, Wagner R, Kamen A: Improving glucose and glutamine metabolism of human HEK 293 and Trichoplusia ni insect cells engineered to express a cytosolic pyruvate carboxylase enzyme. Biotechnol Prog. 2003 Jan-Feb;19(1):90-7.

3(0,0,0,3) Details
19002931 Yallop CA, Norby PL, Jensen R, Reinbach H, Svendsen I: Characterisation of G418-induced metabolic load in recombinant CHO and BHK cells: effect on the activity and expression of central metabolic enzymes. Cytotechnology. 2003 Jul;42(2):87-99.


The activity of glucose-6-phosphate dehydrogenase and pyruvate carboxylase in CHO cells was also increased whilst lactate dehydrogenase activity remained unaltered, suggesting an increased flux to the pentose phosphate pathway and TCA cycle, respectively.
2(0,0,0,2) Details
19896555 Goudar C, Biener R, Boisart C, Heidemann R, Piret J, de Graaf A, Konstantinov K: Metabolic flux analysis of CHO cells in perfusion culture by metabolite balancing and 2D [13C, 1H] COSY NMR spectroscopy. Metab Eng. 2010 Mar;12(2):138-49. Epub 2009 Nov 5.


The anaplerotic conversion of pyruvate to oxaloacetate by pyruvate carboxylase accounted for 10% of the pyruvate flux with the remaining 90% entering the TCA cycle through acetyl-CoA.
2(0,0,0,2) Details
15063626 Fogolin MB, Wagner R, Etcheverrigaray M, Kratje R: Impact of temperature reduction and expression of yeast pyruvate carboxylase on hGM-CSF-producing CHO cells. J Biotechnol. 2004 Apr 8;109(1-2):179-91.

2(0,0,0,2) Details
18469201 Satapati S, He T, Inagaki T, Potthoff M, Merritt ME, Esser V, Mangelsdorf DJ, Kliewer SA, Browning JD, Burgess SC: Partial resistance to peroxisome proliferator-activated receptor-alpha agonists in ZDF rats is associated with defective hepatic mitochondrial metabolism. Diabetes. 2008 Aug;57(8):2012-21. Epub 2008 May 9.


RESULTS: Hepatic mitochondrial fat oxidation in the diabetic liver was impaired twofold secondary to decreased ketogenesis, but tricarboxylic acid (TCA) cycle activity and pyruvate carboxylase flux were normal in newly diabetic rats and elevated in older rats.
2(0,0,0,2) Details
15127163 Segura D, Espin G: Inactivation of pycA, encoding pyruvate carboxylase activity, increases poly-beta-hydroxybutyrate accumulation in Azotobacter vinelandii on solid medium. Appl Microbiol Biotechnol. 2004 Sep;65(4):414-8. Epub 2004 May 4.

2(0,0,0,2) Details
18686030 Murin R, Cesar M, Kowtharapu BS, Verleysdonk S, Hamprecht B: Expression of pyruvate carboxylase in cultured oligodendroglial, microglial and ependymal cells. Neurochem Res. 2009 Mar;34(3):480-9. Epub 2008 Aug 7.

2(0,0,0,2) Details
16269086 Frick O, Wittmann C: Characterization of the metabolic shift between oxidative and fermentative growth in Saccharomyces cerevisiae by comparative 13C flux analysis. Microb Cell Fact. 2005 Nov 3;4:30.


This involved a flux redirection from the pentose phosphate pathway (PPP) towards glycolysis, an increased flux through pyruvate carboxylase, the fermentative pathways and malic enzyme, a flux decrease through the TCA cycle, and a partial relocation of alanine biosynthesis from the mitochondrion to the cytosol.
2(0,0,0,2) Details
16575559 Simpson NE, Khokhlova N, Oca-Cossio JA, Constantinidis I: Insights into the role of anaplerosis in insulin secretion: A 13C NMR study. Diabetologia. 2006 Jun;49(6):1338-48. Epub 2006 Mar 31.


A model containing a single pool of pyruvate, an entrance to the TCA cycle via the pyruvate dehydrogenase complex, and two anaplerotic entrances, one through pyruvate carboxylase and another through an undefined (by the modelling program) source, provided the best fit to the data under all conditions tested, for all cell lines.
2(0,0,0,2) Details
15145544 Hertz L: Intercellular metabolic compartmentation in the brain: past, present and future. Neurochem Int. 2004 Jul-Aug;45(2-3):285-96.


This pool, which was designated 'the small compartment,' is now known to be made up predominantly or exclusively of astrocytes, which accumulate glutamate avidly and express glutamine synthetase activity, whereas this enzyme is absent from neurons, which eventually were established to constitute 'the large compartment.' During the following decades, the metabolic compartment concept was refined, aided by emerging studies of energy metabolism and glutamate uptake in cellularly homogenous preparations and by the histochemical observations that the two key enzymes glutamine synthetase and pyruvate carboxylase are active in astrocytes but absent in neurons.
1(0,0,0,1) Details
17008113 Liu L, Li Y, Zhu Y, Du G, Chen J: Redistribution of carbon flux in Torulopsis glabrata by altering vitamin and calcium level. Metab Eng. 2007 Jan;9(1):21-9. Epub 2006 Aug 12.


Increasing the concentrations of thiamine and biotin could selectively open the valve of carbon flux from pyruvate to pyruvate dehydrogenase complex, the pyruvate carboxylase (PC) pathway and the channel into the TCA cycle, leading to the over-production of alpha-ketoglutarate.
1(0,0,0,1) Details
17940539 Serres S, Raffard G, Franconi JM, Merle M: Close coupling between astrocytic and neuronal metabolisms to fulfill anaplerotic and energy needs in the rat brain. J Cereb Blood Flow Metab. 2008 Apr;28(4):712-24. Epub 2007 Oct 17.


Acetyl-coenzyme A C2 enrichment and ratio between pyruvate carboxylase and pyruvate dehydrogenase activity (PC/PDH) were determined from glutamate and glutamine labeling.
1(0,0,0,1) Details
15183011 Zwingmann C, Leibfritz D, Hazell AS: Brain energy metabolism in a sub-acute rat model of manganese neurotoxicity: an ex vivo nuclear magnetic resonance study using [1-13C] glucose. Neurotoxicology. 2004 Jun;25(4):573-87.


The relative flux of glucose through astrocytic pyruvate carboxylase (PC), on the other hand, was impaired by manganese, as evident from a decreased ratio of [2-13C]/[4-13C] glutamate or [2-13C]/[4-13C] glutamine.
1(0,0,0,1) Details
16496303 Zwingmann C, Bilodeau M: Metabolic insights into the hepatoprotective role of N-acetylcysteine in mouse liver. Hepatology. 2006 Mar;43(3):454-63.


Hepatocellular metabolites and high-energy phosphates were quantified from mouse liver extracts by 1H- and 31P-NMR (nuclear magnetic resonance) spectroscopy. 13C-NMR-isotopomer analysis was used to measure [U-13C] glucose metabolism through pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC).
1(0,0,0,1) Details
12646315 Miccheli A, Puccetti C, Capuani G, Di Cocco ME, Giardino L, Calza L, Battaglia A, Battistin L, Conti F: [1-13C] Glucose entry in neuronal and astrocytic intermediary metabolism of aged rats. Brain Res. 2003 Mar 14;966(1):116-25.


A significant increase in pyruvate carboxylase/pyruvate dehydrogenase activity (PC/PDH) in the synthesis of glutamate in nicergoline-treated aged rats is consistent with an increase in the transport of glutamine from glia to neurons for conversion into glutamate.
1(0,0,0,1) Details
16504342 Haberg A, Qu H, Sonnewald U: Glutamate and GABA metabolism in transient and permanent middle cerebral artery occlusion in rat: importance of astrocytes for neuronal survival. Neurochem Int. 2006 May-Jun;48(6-7):531-40. Epub 2006 Feb 28.


The utilization of astrocytic precursors originating from the pyruvate carboxylase pathway was markedly reduced compared the pyruvate dehydrogenase pathway in glutamate, and completely stopped in GABA.
1(0,0,0,1) Details
15491857 Zamboni N, Maaheimo H, Szyperski T, Hohmann HP, Sauer U: The phosphoenolpyruvate carboxykinase also catalyzes C3 carboxylation at the interface of glycolysis and the TCA cycle of Bacillus subtilis. Metab Eng. 2004 Oct;6(4):277-84.


At least in the industrial strain, we demonstrate the additional capacity of PEP carboxykinase to function as a substitute anaplerotic reaction when the normal pyruvate carboxylase is inactivated.
1(0,0,0,1) Details
19162097 Veit A, Rittmann D, Georgi T, Youn JW, Eikmanns BJ, Wendisch VF: Pathway identification combining metabolic flux and functional genomics analyses: acetate and propionate activation by Corynebacterium glutamicum. J Biotechnol. 2009 Mar 10;140(1-2):75-83. Epub 2008 Dec 27.


Metabolic flux analysis during growth on an acetate-glucose mixture revealed that in the absence of the AK-PTA pathway carbon fluxes in glycolysis, the tricarboxylic acid (TCA) cycle and anaplerosis via PEP carboxylase and/or pyruvate carboxylase were increased, while the glyoxylate cycle flux was decreased.
1(0,0,0,1) Details
15747777 Dote T, Kono K, Usuda K, Shimizu H, Tanimoto Y, Dote E, Hayashi S: Systemic effects and skin injury after experimental dermal exposure to monochloroacetic acid. Toxicol Ind Health. 2003 Oct;19(7-10):165-9.


MCA metabolites also inhibit pyruvate carboxylase in the gluconeogenesis pathway.
1(0,0,0,1) Details
16904360 Forbes NS, Meadows AL, Clark DS, Blanch HW: Estradiol stimulates the biosynthetic pathways of breast cancer cells: detection by metabolic flux analysis. Metab Eng. 2006 Nov;8(6):639-52. Epub 2006 Jun 30.


The metabolic pathway model used by the algorithm includes glycolysis, the tricarboxylic acid cycle (TCA cycle), the pentose phosphate pathway, glutamine catabolism, pyruvate carboxylase, and malic enzyme.
1(0,0,0,1) Details
18339202 Becker J, Klopprogge C, Wittmann C: Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum. Microb Cell Fact. 2008 Mar 13;7:8.


The latter involved a flux shift from pyruvate carboxylase (PC) to PEPC, by which the cell maintained anaplerotic supply of the TCA cycle.
1(0,0,0,1) Details
19376508 Chatziioannou A, Palaiologos G, Kolisis FN: An in-silico model of the biosynthesis of neurotransmitter glutamate, elucidates the complex regulatory role of glucocorticoids in neurotransmitter glutamate release. Comput Biol Med. 2009 Jun;39(6):501-11. Epub 2009 Apr 18.


Estimates of the astrocytic pyruvate carboxylase reaction and the neuronal TCA cycle rates are correlated with different dexamethasone concentrations, in order to extrapolate explicit kinetic equations.
1(0,0,0,1) Details
19788729 Furch T, Preusse M, Tomasch J, Zech H, Wagner-Dobler I, Rabus R, Wittmann C: Metabolic fluxes in the central carbon metabolism of Dinoroseobacter shibae and Phaeobacter gallaeciensis, two members of the marine Roseobacter clade. BMC Microbiol. 2009 Sep 29;9:209.


Moreover, it could be shown that pyruvate carboxylase is involved in CO2 assimilation and that the cyclic respiratory mode of the TCA cycle is utilised.
1(0,0,0,1) Details
12742079 Hertz L, Hertz E: Cataplerotic TCA cycle flux determined as glutamate-sustained oxygen consumption in primary cultures of astrocytes. Neurochem Int. 2003 Sep-Oct;43(4-5):355-61.


This anaplerotic ('pool-filling') process occurs in astrocytes, which in contrast to neurons express pyruvate carboxylase (PC) activity.
1(0,0,0,1) Details
12526195 Karavaiko GI, Zakharchuk LM, Bogdanova TI, Egorova MA, Tsaplina IA, Krasil'nikova EN: [The enzyme of carbon metabolism in the thermotolerant sulfobacillus strain K1]. Mikrobiologiia. 2002 Nov-Dec;71(6):755-61.


The activities of pyruvate carboxylase, phosphoenolpyruvate carboxylase, phosphoenolpyruvate carboxykinase, and phosphoenolpyruvate carboxytransphosphorylase decreased with the increasing content of CO2 in the medium.
1(0,0,0,1) Details
15903243 Benslimane C, Elias CB, Hawari J, Kamen A: Insights into the central metabolism of Spodoptera frugiperda (Sf-9) and Trichoplusia ni BTI-Tn-5B1-4 (Tn-5) insect cells by radiolabeling studies. Biotechnol Prog. 2005 Jan-Feb;21(1):78-86.


Furthermore, the changes in the metabolic fluxes of glucose and glutamine in Tn-5-PYC cells, which have been engineered to express a cytosolic pyruvate carboxylase, have been studied and compared to the unmodified cells Tn-5.
1(0,0,0,1) Details
16765624 Simpson NE, Han Z, Berendzen KM, Sweeney CA, Oca-Cossio JA, Constantinidis I, Stacpoole PW: Magnetic resonance spectroscopic investigation of mitochondrial fuel metabolism and energetics in cultured human fibroblasts: effects of pyruvate dehydrogenase complex deficiency and dichloroacetate. Mol Genet Metab. 2006 Sep-Oct;89(1-2):97-105. Epub 2006 Jun 12.


In all cells, DCA caused a major shift (40% decrease) from anaplerotic-related pathways (e.g., pyruvate carboxylase) toward flux through PDC.
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17263682 Bartnik BL, Hovda DA, Lee PW: Glucose metabolism after traumatic brain injury: estimation of pyruvate carboxylase and pyruvate dehydrogenase flux by mass isotopomer analysis. J Neurotrauma. 2007 Jan;24(1):181-94.

1(0,0,0,1) Details
15601933 Oz G, Berkich DA, Henry PG, Xu Y, LaNoue K, Hutson SM, Gruetter R: Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity. J Neurosci. 2004 Dec 15;24(50):11273-9.


A high pyruvate carboxylase rate (V (PC), approximately 0.14-0.18 micromol x gm (-1) x min (-1)) contributed to the glial TCA cycle flux.
1(0,0,0,1) Details