Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1999 May 15;340(Pt 1):1–16. doi: 10.1042/bj3400001

Structure, function and regulation of pyruvate carboxylase.

S Jitrapakdee 1, J C Wallace 1
PMCID: PMC1220216  PMID: 10229653

Abstract

Pyruvate carboxylase (PC; EC 6.4.1.1), a member of the biotin-dependent enzyme family, catalyses the ATP-dependent carboxylation of pyruvate to oxaloacetate. PC has been found in a wide variety of prokaryotes and eukaryotes. In mammals, PC plays a crucial role in gluconeogenesis and lipogenesis, in the biosynthesis of neurotransmitter substances, and in glucose-induced insulin secretion by pancreatic islets. The reaction catalysed by PC and the physical properties of the enzyme have been studied extensively. Although no high-resolution three-dimensional structure has yet been determined by X-ray crystallography, structural studies of PC have been conducted by electron microscopy, by limited proteolysis, and by cloning and sequencing of genes and cDNA encoding the enzyme. Most well characterized forms of active PC consist of four identical subunits arranged in a tetrahedron-like structure. Each subunit contains three functional domains: the biotin carboxylation domain, the transcarboxylation domain and the biotin carboxyl carrier domain. Different physiological conditions, including diabetes, hyperthyroidism, genetic obesity and postnatal development, increase the level of PC expression through transcriptional and translational mechanisms, whereas insulin inhibits PC expression. Glucocorticoids, glucagon and catecholamines cause an increase in PC activity or in the rate of pyruvate carboxylation in the short term. Molecular defects of PC in humans have recently been associated with four point mutations within the structural region of the PC gene, namely Val145-->Ala, Arg451-->Cys, Ala610-->Thr and Met743-->Thr.

Full Text

The Full Text of this article is available as a PDF (395.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adam P. A., Haynes R. C., Jr Control of hepatic mitochondrial CO2 fixation by glucagon, epinephrine, and cortisol. J Biol Chem. 1969 Dec 10;244(23):6444–6450. [PubMed] [Google Scholar]
  2. Ahmad P. M., Russell T. R., Ahmad F. Increase in fatty acid synthetase content of 3T3-L cells undergoing spontaneous and chemically induced differentiation to adipocytes. Biochem J. 1979 Aug 15;182(2):509–514. doi: 10.1042/bj1820509. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Al-Feel W., Chirala S. S., Wakil S. J. Cloning of the yeast FAS3 gene and primary structure of yeast acetyl-CoA carboxylase. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4534–4538. doi: 10.1073/pnas.89.10.4534. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res. 1997 Sep 1;25(17):3389–3402. doi: 10.1093/nar/25.17.3389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Angus C. W., Lane M. D., Rosenfeld P. J., Kelly T. J. Increase in translatable mRNA for mitochondrial pyruvate carboxylase during differentiation of 3T3 preadipocytes. Biochem Biophys Res Commun. 1981 Dec 31;103(4):1216–1222. doi: 10.1016/0006-291x(81)90252-7. [DOI] [PubMed] [Google Scholar]
  6. Artymiuk P. J., Poirrette A. R., Rice D. W., Willett P. Biotin carboxylase comes into the fold. Nat Struct Biol. 1996 Feb;3(2):128–132. doi: 10.1038/nsb0296-128. [DOI] [PubMed] [Google Scholar]
  7. Ashcroft F. M., Harrison D. E., Ashcroft S. J. Glucose induces closure of single potassium channels in isolated rat pancreatic beta-cells. 1984 Nov 29-Dec 5Nature. 312(5993):446–448. doi: 10.1038/312446a0. [DOI] [PubMed] [Google Scholar]
  8. Ashman L. K., Keech D. B. Sheep kidney pyruvate carboxylase. Studies on the coupling of adenosine triphosphate hydrolysis and CO2 fixation. J Biol Chem. 1975 Jan 10;250(1):14–21. [PubMed] [Google Scholar]
  9. Ashman L. K., Keech D. B., Wallace J. C., Nielsen J. Sheep kidney pyruvate carboxylase. Studies on its activation by acetyl coenzyme A and characteristics of its acetyl coenzyme A independent reaction. J Biol Chem. 1972 Sep 25;247(18):5818–5824. [PubMed] [Google Scholar]
  10. Ashman L. K., Wallace J. C., Keech D. B. Densitization of pyruvate carboxylase against acetyl-CoA stimulation by chemical modification. Biochem Biophys Res Commun. 1973 Apr 16;51(4):924–931. doi: 10.1016/0006-291x(73)90015-6. [DOI] [PubMed] [Google Scholar]
  11. Ashworth J. M., Kornberg H. L. The anaplerotic fixation of carbon dioxide by Escherichia coli. Proc R Soc Lond B Biol Sci. 1966 Aug 16;165(999):179–188. doi: 10.1098/rspb.1966.0063. [DOI] [PubMed] [Google Scholar]
  12. Athappilly F. K., Hendrickson W. A. Structure of the biotinyl domain of acetyl-coenzyme A carboxylase determined by MAD phasing. Structure. 1995 Dec 15;3(12):1407–1419. doi: 10.1016/s0969-2126(01)00277-5. [DOI] [PubMed] [Google Scholar]
  13. Atkin B. M., Utter M. F., Weinberg M. B. Pyruvate carboxylase and phosphoenolpyruvate carboxykinase activity in leukocytes and fibroblasts from a patient with pyruvate carboxylase deficiency. Pediatr Res. 1979 Jan;13(1):38–43. doi: 10.1203/00006450-197901000-00009. [DOI] [PubMed] [Google Scholar]
  14. Attwood P. V., Cleland W. W. Decarboxylation of oxalacetate by pyruvate carboxylase. Biochemistry. 1986 Dec 16;25(25):8191–8196. doi: 10.1021/bi00373a011. [DOI] [PubMed] [Google Scholar]
  15. Attwood P. V., Graneri B. D. Bicarbonate-dependent ATP cleavage catalysed by pyruvate carboxylase in the absence of pyruvate. Biochem J. 1992 Nov 1;287(Pt 3):1011–1017. doi: 10.1042/bj2871011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Attwood P. V., Graneri B. D. Pyruvate carboxylase catalysis of phosphate transfer between carbamoyl phosphate and ADP. Biochem J. 1991 Jan 15;273(Pt 2):443–448. doi: 10.1042/bj2730443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Attwood P. V., Johannssen W., Chapman-Smith A., Wallace J. C. The existence of multiple tetrameric conformers of chicken liver pyruvate carboxylase and their roles in dilution inactivation. Biochem J. 1993 Mar 1;290(Pt 2):583–590. doi: 10.1042/bj2900583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Attwood P. V. Locus of action of acetyl CoA in the biotin-carboxylation reaction of pyruvate carboxylase. Biochemistry. 1993 Nov 30;32(47):12736–12742. doi: 10.1021/bi00210a024. [DOI] [PubMed] [Google Scholar]
  19. Attwood P. V., Mayer F., Wallace J. C. Avidin as a probe of the conformational changes induced in pyruvate carboxylase by acetyl-CoA and pyruvate. FEBS Lett. 1986 Jul 28;203(2):191–196. doi: 10.1016/0014-5793(86)80740-2. [DOI] [PubMed] [Google Scholar]
  20. Attwood P. V. The structure and the mechanism of action of pyruvate carboxylase. Int J Biochem Cell Biol. 1995 Mar;27(3):231–249. doi: 10.1016/1357-2725(94)00087-r. [DOI] [PubMed] [Google Scholar]
  21. Attwood P. V., Tipton P. A., Cleland W. W. Carbon-13 and deuterium isotope effects on oxalacetate decarboxylation by pyruvate carboxylase. Biochemistry. 1986 Dec 16;25(25):8197–8205. doi: 10.1021/bi00373a012. [DOI] [PubMed] [Google Scholar]
  22. BALLARD F. J., OLIVER I. T. CARBOHYDRATE METABOLISM IN LIVER FROM FOETAL AND NEONATAL SHEEP. Biochem J. 1965 Apr;95:191–200. doi: 10.1042/bj0950191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. BARNETT J. A., KORNBERG H. L. The utilization by yeasts of acids of the tricarboxylic acid cycle. J Gen Microbiol. 1960 Aug;23:65–82. doi: 10.1099/00221287-23-1-65. [DOI] [PubMed] [Google Scholar]
  24. BLOOM S. J., JOHNSON M. J. The pyruvate carboxylase of Aspergillus niger. J Biol Chem. 1962 Sep;237:2718–2720. [PubMed] [Google Scholar]
  25. Bais R., Keech B. The magnesium ion (Mg 2+ ) activation of sheep kidney pyruvate carboxylase. J Biol Chem. 1972 May 25;247(10):3255–3261. [PubMed] [Google Scholar]
  26. Ballard F. J., Hanson R. W., Kronfeld D. S. Factors controlling the concentration of mitochondrial oxaloacetate in liver during spontaneous bovine ketosis. Biochem Biophys Res Commun. 1968 Jan 11;30(1):100–104. doi: 10.1016/0006-291x(68)90719-5. [DOI] [PubMed] [Google Scholar]
  27. Ballard F. J., Hanson R. W. Phosphoenolpyruvate carboxykinase and pyruvate carboxylase in developing rat liver. Biochem J. 1967 Sep;104(3):866–871. doi: 10.1042/bj1040866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Ballard F. J., Hanson R. W. The citrate cleavage pathway and lipogenesis in rat adipose tissue: replenishment of oxaloacetate. J Lipid Res. 1967 Mar;8(2):73–79. [PubMed] [Google Scholar]
  29. Barden R. E., Scrutton M. C. Pyruvate carboxylase from chicken liver. Effects of univalent and divalent cations on catalytic activity. J Biol Chem. 1974 Aug 10;249(15):4829–4838. [PubMed] [Google Scholar]
  30. Benjamin A. M., Quastel J. H. Fate of L-glutamate in the brain. J Neurochem. 1974 Sep;23(3):457–464. doi: 10.1111/j.1471-4159.1974.tb06046.x. [DOI] [PubMed] [Google Scholar]
  31. Berry M. N., Phillips J. W., Grivell A. R. Interactions between mitochondria and cytoplasm in isolated hepatocytes. Curr Top Cell Regul. 1992;33:309–328. doi: 10.1016/b978-0-12-152833-1.50023-x. [DOI] [PubMed] [Google Scholar]
  32. Brewster N. K., Val D. L., Walker M. E., Wallace J. C. Regulation of pyruvate carboxylase isozyme (PYC1, PYC2) gene expression in Saccharomyces cerevisiae during fermentative and nonfermentative growth. Arch Biochem Biophys. 1994 May 15;311(1):62–71. doi: 10.1006/abbi.1994.1209. [DOI] [PubMed] [Google Scholar]
  33. Brocklehurst S. M., Perham R. N. Prediction of the three-dimensional structures of the biotinylated domain from yeast pyruvate carboxylase and of the lipoylated H-protein from the pea leaf glycine cleavage system: a new automated method for the prediction of protein tertiary structure. Protein Sci. 1993 Apr;2(4):626–639. doi: 10.1002/pro.5560020413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Böttger I., Kriegel H., Wieland O. Fluctuation of hepatic enzymes important in glucose metabolism in relation to thyroid function. Eur J Biochem. 1970 Apr;13(2):253–257. doi: 10.1111/j.1432-1033.1970.tb00925.x. [DOI] [PubMed] [Google Scholar]
  35. Böttger I., Wieland O., Brdiczka D., Pette D. Intracellular localization of pyruvate carboxylase and phosphoenolpyruvate carboxykinase in rat liver. Eur J Biochem. 1969 Mar;8(1):113–119. doi: 10.1111/j.1432-1033.1969.tb00503.x. [DOI] [PubMed] [Google Scholar]
  36. Carbone M. A., MacKay N., Ling M., Cole D. E., Douglas C., Rigat B., Feigenbaum A., Clarke J. T., Haworth J. C., Greenberg C. R. Amerindian pyruvate carboxylase deficiency is associated with two distinct missense mutations. Am J Hum Genet. 1998 Jun;62(6):1312–1319. doi: 10.1086/301884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Carver J. A., Baldwin G. S., Keech D. B., Bais R., Wallace J. C. Inactivation of chicken liver pyruvate carboxylase by 1,10-phenanthroline. Biochem J. 1988 Jun 1;252(2):501–507. doi: 10.1042/bj2520501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Cazzulo J. J., Stoppani A. O. The regulation of yeast pyruvate carboxylase by acetyl-coenzyme A and L-aspartate. Arch Biochem Biophys. 1968 Sep 20;127(1):563–567. doi: 10.1016/0003-9861(68)90263-4. [DOI] [PubMed] [Google Scholar]
  39. Cazzulo J. J., Sundaram T. K., Dilks S. N., Kornberg H. L. Synthesis of pyruvate carboxylase from its apoenzyme and (+)-biotin in Bacillus stearothermophilus. Purification and properties of the apoenzyme and the holoenzyme synthetase. Biochem J. 1971 May;122(5):653–661. doi: 10.1042/bj1220653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Chandler C. S., Ballard F. J. Distribution and degradation of biotin-containing carboxylases in human cell lines. Biochem J. 1985 Dec 1;232(2):385–393. doi: 10.1042/bj2320385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Chandler C. S., Ballard F. J. Multiple biotin-containing proteins in 3T3-L1 cells. Biochem J. 1986 Jul 1;237(1):123–130. doi: 10.1042/bj2370123. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Chang H. I., Cohen N. D. Regulation and intracellular localization of the biotin holocarboxylase synthetase of 3T3-L1 cells. Arch Biochem Biophys. 1983 Aug;225(1):237–247. doi: 10.1016/0003-9861(83)90026-7. [DOI] [PubMed] [Google Scholar]
  43. Chapatwala K. D., Boykin M., Butts A., Rajanna B. Effect of intraperitoneally injected cadmium on renal and hepatic gluconeogenic enzymes in rats. Drug Chem Toxicol. 1982;5(3):305–317. doi: 10.3109/01480548209041060. [DOI] [PubMed] [Google Scholar]
  44. Chapatwala K. D., Rajanna B., Desaiah D. Cadmium induced changes in gluconeogenic enzymes in rat kidney and liver. Drug Chem Toxicol. 1980;3(4):407–420. doi: 10.3109/01480548009030129. [DOI] [PubMed] [Google Scholar]
  45. Chapman-Smith A., Booker G. W., Clements P. R., Wallace J. C., Keech D. B. Further studies on the localization of the reactive lysyl residue of pyruvate carboxylase. Biochem J. 1991 Jun 15;276(Pt 3):759–764. doi: 10.1042/bj2760759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Chapman-Smith A., Forbes B. E., Wallace J. C., Cronan J. E., Jr Covalent modification of an exposed surface turn alters the global conformation of the biotin carrier domain of Escherichia coli acetyl-CoA carboxylase. J Biol Chem. 1997 Oct 10;272(41):26017–26022. doi: 10.1074/jbc.272.41.26017. [DOI] [PubMed] [Google Scholar]
  47. Ciprés G., Urcelay E., Butta N., Ayuso M. S., Parrilla R., Martín-Requero A. Loss of fatty acid control of gluconeogenesis and PDH complex flux in adrenalectomized rats. Am J Physiol. 1994 Oct;267(4 Pt 1):E528–E536. doi: 10.1152/ajpendo.1994.267.4.E528. [DOI] [PubMed] [Google Scholar]
  48. Cooper A. J., Plum F. Biochemistry and physiology of brain ammonia. Physiol Rev. 1987 Apr;67(2):440–519. doi: 10.1152/physrev.1987.67.2.440. [DOI] [PubMed] [Google Scholar]
  49. Cullingford T. E., Dolphin C. T., Bhakoo K. K., Peuchen S., Canevari L., Clark J. B. Molecular cloning of rat mitochondrial 3-hydroxy-3-methylglutaryl-CoA lyase and detection of the corresponding mRNA and of those encoding the remaining enzymes comprising the ketogenic 3-hydroxy-3-methylglutaryl-CoA cycle in central nervous system of suckling rat. Biochem J. 1998 Jan 15;329(Pt 2):373–381. doi: 10.1042/bj3290373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Dardel F., Davis A. L., Laue E. D., Perham R. N. Three-dimensional structure of the lipoyl domain from Bacillus stearothermophilus pyruvate dehydrogenase multienzyme complex. J Mol Biol. 1993 Feb 20;229(4):1037–1048. doi: 10.1006/jmbi.1993.1103. [DOI] [PubMed] [Google Scholar]
  51. De Vos A., Heimberg H., Quartier E., Huypens P., Bouwens L., Pipeleers D., Schuit F. Human and rat beta cells differ in glucose transporter but not in glucokinase gene expression. J Clin Invest. 1995 Nov;96(5):2489–2495. doi: 10.1172/JCI118308. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Doolittle R. F. The multiplicity of domains in proteins. Annu Rev Biochem. 1995;64:287–314. doi: 10.1146/annurev.bi.64.070195.001443. [DOI] [PubMed] [Google Scholar]
  53. Dunn M. F., Araíza G., Cevallos M. A., Mora J. Regulation of pyruvate carboxylase in Rhizobium etli. FEMS Microbiol Lett. 1997 Dec 15;157(2):301–306. doi: 10.1111/j.1574-6968.1997.tb12789.x. [DOI] [PubMed] [Google Scholar]
  54. Dunn M. F., Encarnación S., Araíza G., Vargas M. C., Dávalos A., Peralta H., Mora Y., Mora J. Pyruvate carboxylase from Rhizobium etli: mutant characterization, nucleotide sequence, and physiological role. J Bacteriol. 1996 Oct;178(20):5960–5970. doi: 10.1128/jb.178.20.5960-5970.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Easterbrook-Smith S. B., Hudson P. J., Goss N. H., Keech D. B., Wallace J. C. Pyruvate carboxylase: mechanism on the second partial reaction. Arch Biochem Biophys. 1976 Oct;176(2):709–720. doi: 10.1016/0003-9861(76)90215-0. [DOI] [PubMed] [Google Scholar]
  56. Faff-Michalak L., Albrecht J. Aspartate aminotransferase, malate dehydrogenase, and pyruvate carboxylase activities in rat cerebral synaptic and nonsynaptic mitochondria: effects of in vitro treatment with ammonia, hyperammonemia and hepatic encephalopathy. Metab Brain Dis. 1991 Dec;6(4):187–197. doi: 10.1007/BF00996918. [DOI] [PubMed] [Google Scholar]
  57. Fahien L. A., Davis J. W., Laboy J. Interactions between pyruvate carboxylase and other mitochondrial enzymes. J Biol Chem. 1993 Aug 25;268(24):17935–17942. [PubMed] [Google Scholar]
  58. Fan C., Moews P. C., Walsh C. T., Knox J. R. Vancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution. Science. 1994 Oct 21;266(5184):439–443. doi: 10.1126/science.7939684. [DOI] [PubMed] [Google Scholar]
  59. Filsell O. H., Jarrett I. G., Taylor P. H., Keech D. B. Effects of fasting, diabetes and glucocorticoids on gluconeogenic enzymes in the sheep. Biochim Biophys Acta. 1969 Jun 17;184(1):54–63. doi: 10.1016/0304-4165(69)90098-1. [DOI] [PubMed] [Google Scholar]
  60. Flores C. L., Gancedo C. Expression of PEP carboxylase from Escherichia coli complements the phenotypic effects of pyruvate carboxylase mutations in Saccharomyces cerevisiae. FEBS Lett. 1997 Aug 4;412(3):531–534. doi: 10.1016/s0014-5793(97)00854-5. [DOI] [PubMed] [Google Scholar]
  61. Frey W. H., 2nd, Utter M. F. Binding of acetyl-CoA to chicken liver pyruvate carboxylase. J Biol Chem. 1977 Jan 10;252(1):51–56. [PubMed] [Google Scholar]
  62. Freytag S. O., Collier K. J. Molecular cloning of a cDNA for human pyruvate carboxylase. Structural relationship to other biotin-containing carboxylases and regulation of mRNA content in differentiating preadipocytes. J Biol Chem. 1984 Oct 25;259(20):12831–12837. [PubMed] [Google Scholar]
  63. Freytag S. O., Utter M. F. Induction of pyruvate carboxylase apoenzyme and holoenzyme in 3T3-L1 cells during differentiation. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1321–1325. doi: 10.1073/pnas.77.3.1321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Freytag S. O., Utter M. F. Regulation of the synthesis and degradation of pyruvate carboxylase in 3T3-L1 cells. J Biol Chem. 1983 May 25;258(10):6307–6312. [PubMed] [Google Scholar]
  65. Friedmann N., Exton J. H., Park C. R. Interaction of adrenal steroids and glucagon on gluconeogenesis in perfused rat liver. Biochem Biophys Res Commun. 1967 Oct 11;29(1):113–119. doi: 10.1016/0006-291x(67)90550-5. [DOI] [PubMed] [Google Scholar]
  66. Fuchs J., Johannssen W., Rohde M., Mayer F. Pyruvate carboxylase from Pseudomonas citronellolis: shape of the enzyme, and localization of its prosthetic biotin group by electron microscopic affinity labeling. FEBS Lett. 1988 Apr 11;231(1):102–106. doi: 10.1016/0014-5793(88)80711-7. [DOI] [PubMed] [Google Scholar]
  67. Gamberino W. C., Berkich D. A., Lynch C. J., Xu B., LaNoue K. F. Role of pyruvate carboxylase in facilitation of synthesis of glutamate and glutamine in cultured astrocytes. J Neurochem. 1997 Dec;69(6):2312–2325. doi: 10.1046/j.1471-4159.1997.69062312.x. [DOI] [PubMed] [Google Scholar]
  68. Gancedo J. M. Carbon catabolite repression in yeast. Eur J Biochem. 1992 Jun 1;206(2):297–313. doi: 10.1111/j.1432-1033.1992.tb16928.x. [DOI] [PubMed] [Google Scholar]
  69. Garrison J. C., Borland M. K. Regulation of mitochondrial pyruvate carboxylation and gluconeogenesis in rat hepatocytes via an alpha-adrenergic, adenosine 3':5'-monophosphate-independent mechanism. J Biol Chem. 1979 Feb 25;254(4):1129–1133. [PubMed] [Google Scholar]
  70. Garrison J. C., Haynes R. C., Jr The hormonal control of gluconeogenesis by regulation of mitochondrial pyruvate carboxylation in isolated rat liver cells. J Biol Chem. 1975 Apr 25;250(8):2769–2777. [PubMed] [Google Scholar]
  71. Girard J., Ferré P., Pégorier J. P., Duée P. H. Adaptations of glucose and fatty acid metabolism during perinatal period and suckling-weaning transition. Physiol Rev. 1992 Apr;72(2):507–562. doi: 10.1152/physrev.1992.72.2.507. [DOI] [PubMed] [Google Scholar]
  72. Goodall G. J., Baldwin G. S., Wallace J. C., Keech D. B. Factors that influence the translocation of the N-carboxybiotin moiety between the two sub-sites of pyruvate carboxylase. Biochem J. 1981 Dec 1;199(3):603–609. doi: 10.1042/bj1990603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  73. Goss J. A., Cohen N. D., Utter M. F. Characterization of the subunit structure of pyruvate carboxylase from Pseudomonas citronellolis. J Biol Chem. 1981 Nov 25;256(22):11819–11825. [PubMed] [Google Scholar]
  74. Green J. D., Laue E. D., Perham R. N., Ali S. T., Guest J. R. Three-dimensional structure of a lipoyl domain from the dihydrolipoyl acetyltransferase component of the pyruvate dehydrogenase multienzyme complex of Escherichia coli. J Mol Biol. 1995 Apr 28;248(2):328–343. doi: 10.1016/s0022-2836(95)80054-9. [DOI] [PubMed] [Google Scholar]
  75. Ha J., Daniel S., Kong I. S., Park C. K., Tae H. J., Kim K. H. Cloning of human acetyl-CoA carboxylase cDNA. Eur J Biochem. 1994 Jan 15;219(1-2):297–306. doi: 10.1111/j.1432-1033.1994.tb19941.x. [DOI] [PubMed] [Google Scholar]
  76. Haarasilta S., Oura E. Effect of aeration on the activity of gluconeogenetic enzymes in Saccharomyces cerevisiae growing under glucose limitation. Arch Microbiol. 1975 Dec 31;106(3):271–273. doi: 10.1007/BF00446534. [DOI] [PubMed] [Google Scholar]
  77. Halestrap A. P., Armston A. E. A re-evaluation of the role of mitochondrial pyruvate transport in the hormonal control of rat liver mitochondrial pyruvate metabolism. Biochem J. 1984 Nov 1;223(3):677–685. doi: 10.1042/bj2230677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  78. Halestrap A. P. Stimulation of pyruvate transport in metabolizing mitochondria through changes in the transmembrane pH gradient induced by glucagon treatment of rats. Biochem J. 1978 Jun 15;172(3):389–398. doi: 10.1042/bj1720389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Heimberg H., De Vos A., Vandercammen A., Van Schaftingen E., Pipeleers D., Schuit F. Heterogeneity in glucose sensitivity among pancreatic beta-cells is correlated to differences in glucose phosphorylation rather than glucose transport. EMBO J. 1993 Jul;12(7):2873–2879. doi: 10.1002/j.1460-2075.1993.tb05949.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Hobbs S., Jitrapakdee S., Wallace J. C. Development of a bicistronic vector driven by the human polypeptide chain elongation factor 1alpha promoter for creation of stable mammalian cell lines that express very high levels of recombinant proteins. Biochem Biophys Res Commun. 1998 Nov 18;252(2):368–372. doi: 10.1006/bbrc.1998.9646. [DOI] [PubMed] [Google Scholar]
  81. Irias J. J., Olmsted M. R., Utter M. F. Pyruvate carboxylase. Reversible inactivation by cold. Biochemistry. 1969 Dec;8(12):5136–5148. doi: 10.1021/bi00840a068. [DOI] [PubMed] [Google Scholar]
  82. Javid-Majd F., Stapleton M. A., Harmon M. F., Hanks B. A., Mullins L. S., Raushel F. M. Comparison of the functional differences for the homologous residues within the carboxy phosphate and carbamate domains of carbamoyl phosphate synthetase. Biochemistry. 1996 Nov 12;35(45):14362–14369. doi: 10.1021/bi961184q. [DOI] [PubMed] [Google Scholar]
  83. Jitrapakdee S., Booker G. W., Cassady A. I., Wallace J. C. Cloning, sequencing and expression of rat liver pyruvate carboxylase. Biochem J. 1996 Jun 1;316(Pt 2):631–637. doi: 10.1042/bj3160631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Jitrapakdee S., Booker G. W., Cassady A. I., Wallace J. C. The rat pyruvate carboxylase gene structure. Alternate promoters generate multiple transcripts with the 5'-end heterogeneity. J Biol Chem. 1997 Aug 15;272(33):20522–20530. doi: 10.1074/jbc.272.33.20522. [DOI] [PubMed] [Google Scholar]
  85. Jitrapakdee S., Gong Q., MacDonald M. J., Wallace J. C. Regulation of rat pyruvate carboxylase gene expression by alternate promoters during development, in genetically obese rats and in insulin-secreting cells. Multiple transcripts with 5'-end heterogeneity modulate translation. J Biol Chem. 1998 Dec 18;273(51):34422–34428. doi: 10.1074/jbc.273.51.34422. [DOI] [PubMed] [Google Scholar]
  86. Jitrapakdee S., Walker M. E., Wallace J. C. Identification of novel alternatively spliced pyruvate carboxylase mRNAs with divergent 5'-untranslated regions which are expressed in a tissue-specific manner. Biochem Biophys Res Commun. 1996 Jun 25;223(3):695–700. doi: 10.1006/bbrc.1996.0958. [DOI] [PubMed] [Google Scholar]
  87. Johannssen W., Attwood P. V., Wallace J. C., Keech D. B. Localisation of the active site of pyruvate carboxylase by electron microscopic examination of avidin-enzyme complexes. Eur J Biochem. 1983 Jun 1;133(1):201–206. doi: 10.1111/j.1432-1033.1983.tb07448.x. [DOI] [PubMed] [Google Scholar]
  88. Jones C. G., Hothi S. K., Titheradge M. A. Effect of dexamethasone on gluconeogenesis, pyruvate kinase, pyruvate carboxylase and pyruvate dehydrogenase flux in isolated hepatocytes. Biochem J. 1993 Feb 1;289(Pt 3):821–828. doi: 10.1042/bj2890821. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Keech B., Barritt G. J. Allosteric activation of sheep kidney pyruvate carboxylase by the magnesium ion (Mg2+) and the magnesium adenosine triphosphate ion (MgATP2-). J Biol Chem. 1967 May 10;242(9):1983–1987. [PubMed] [Google Scholar]
  90. Khew-Goodall Y. S., Johannssen W., Attwood P. V., Wallace J. C., Keech D. B. Studies on dilution inactivation of sheep liver pyruvate carboxylase. Arch Biochem Biophys. 1991 Jan;284(1):98–105. doi: 10.1016/0003-9861(91)90269-o. [DOI] [PubMed] [Google Scholar]
  91. Knowles J. R. The mechanism of biotin-dependent enzymes. Annu Rev Biochem. 1989;58:195–221. doi: 10.1146/annurev.bi.58.070189.001211. [DOI] [PubMed] [Google Scholar]
  92. Koffas M. A., Ramamoorthi R., Pine W. A., Sinskey A. J., Stephanopoulos G. Sequence of the Corynebacterium glutamicum pyruvate carboxylase gene. Appl Microbiol Biotechnol. 1998 Sep;50(3):346–352. doi: 10.1007/s002530051302. [DOI] [PubMed] [Google Scholar]
  93. Kondo H., Kazuta Y., Saito A., Fuji K. Cloning and nucleotide sequence of Bacillus stearothermophilus pyruvate carboxylase. Gene. 1997 May 20;191(1):47–50. doi: 10.1016/s0378-1119(97)00027-9. [DOI] [PubMed] [Google Scholar]
  94. Kraus-Friedmann N., Feng L. The role of intracellular Ca2+ in the regulation of gluconeogenesis. Metabolism. 1996 Mar;45(3):389–403. doi: 10.1016/s0026-0495(96)90296-6. [DOI] [PubMed] [Google Scholar]
  95. Kumar G. K., Haase F. C., Phillips N. F., Wood H. G. Involvement and identification of a tryptophanyl residue at the pyruvate binding site of transcarboxylase. Biochemistry. 1988 Aug 9;27(16):5978–5983. doi: 10.1021/bi00416a022. [DOI] [PubMed] [Google Scholar]
  96. Kunst F., Ogasawara N., Moszer I., Albertini A. M., Alloni G., Azevedo V., Bertero M. G., Bessières P., Bolotin A., Borchert S. The complete genome sequence of the gram-positive bacterium Bacillus subtilis. Nature. 1997 Nov 20;390(6657):249–256. doi: 10.1038/36786. [DOI] [PubMed] [Google Scholar]
  97. LANE M. D., ROMINGER K. L., YOUNG D. L., LYNEN F. THE ENZYMATIC SYNTHESIS OF HOLOTRANSCARBOXYLASE FROM APOTRANSCARBOXYLASE AND (+)-BIOTIN. II. INVESTIGATION OF THE REACTION MECHANISM. J Biol Chem. 1964 Sep;239:2865–2871. [PubMed] [Google Scholar]
  98. Lamhonwah A. M., Barankiewicz T. J., Willard H. F., Mahuran D. J., Quan F., Gravel R. A. Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4864–4868. doi: 10.1073/pnas.83.13.4864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Lehn D. A., Moran S. M., MacDonald M. J. The sequence of the rat pyruvate carboxylase-encoding cDNA. Gene. 1995 Nov 20;165(2):331–332. doi: 10.1016/0378-1119(95)00557-m. [DOI] [PubMed] [Google Scholar]
  100. Leiter A. B., Weinberg M., Isohashi F., Utter M. F. Relationshiop between phosphorylation and activity of pyruvate dehydrogenase in rat liver mitochondria and the absence of such a relationship for pyruvate carboxylase. J Biol Chem. 1978 Apr 25;253(8):2716–2723. [PubMed] [Google Scholar]
  101. Lemons J. A., Moorehead H. C., Hage G. P. Effects of fasting on gluconeogenic enzymes in the ovine fetus. Pediatr Res. 1986 Jul;20(7):676–679. doi: 10.1203/00006450-198607000-00020. [DOI] [PubMed] [Google Scholar]
  102. Leon-Del-Rio A., Gravel R. A. Sequence requirements for the biotinylation of carboxyl-terminal fragments of human propionyl-CoA carboxylase alpha subunit expressed in Escherichia coli. J Biol Chem. 1994 Sep 16;269(37):22964–22968. [PubMed] [Google Scholar]
  103. Li S. J., Cronan J. E., Jr The gene encoding the biotin carboxylase subunit of Escherichia coli acetyl-CoA carboxylase. J Biol Chem. 1992 Jan 15;267(2):855–863. [PubMed] [Google Scholar]
  104. Liang Y., Najafi H., Smith R. M., Zimmerman E. C., Magnuson M. A., Tal M., Matschinsky F. M. Concordant glucose induction of glucokinase, glucose usage, and glucose-stimulated insulin release in pancreatic islets maintained in organ culture. Diabetes. 1992 Jul;41(7):792–806. doi: 10.2337/diab.41.7.792. [DOI] [PubMed] [Google Scholar]
  105. Liao V. H., Freedman J. H. Cadmium-regulated genes from the nematode Caenorhabditis elegans. Identification and cloning of new cadmium-responsive genes by differential display. J Biol Chem. 1998 Nov 27;273(48):31962–31970. doi: 10.1074/jbc.273.48.31962. [DOI] [PubMed] [Google Scholar]
  106. Libor S. M., Sundaram T. K., Scrutton M. C. Pyruvate carboxylase from a thermophilic Bacillus. Studies on the specificity of activation by acyl derivatives of coenzyme A and on the properties of catalysis in the absence of activator. Biochem J. 1978 Mar 1;169(3):543–558. doi: 10.1042/bj1690543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  107. Lim F., Morris C. P., Occhiodoro F., Wallace J. C. Sequence and domain structure of yeast pyruvate carboxylase. J Biol Chem. 1988 Aug 15;263(23):11493–11497. [PubMed] [Google Scholar]
  108. Liu F., Fromm H. J. Purification and characterization of fructose-1,6-bisphosphatase from bovine brain. Arch Biochem Biophys. 1988 Feb 1;260(2):609–615. doi: 10.1016/0003-9861(88)90488-2. [DOI] [PubMed] [Google Scholar]
  109. Lusty C. J., Widgren E. E., Broglie K. E., Nyunoya H. Yeast carbamyl phosphate synthetase. Structure of the yeast gene and homology to Escherichia coli carbamyl phosphate synthetase. J Biol Chem. 1983 Dec 10;258(23):14466–14477. [PubMed] [Google Scholar]
  110. Lynch C. J., McCall K. M., Billingsley M. L., Bohlen L. M., Hreniuk S. P., Martin L. F., Witters L. A., Vannucci S. J. Pyruvate carboxylase in genetic obesity. Am J Physiol. 1992 May;262(5 Pt 1):E608–E618. doi: 10.1152/ajpendo.1992.262.5.E608. [DOI] [PubMed] [Google Scholar]
  111. MacDonald M. J., Chang C. M. Do pancreatic islets contain significant amounts of phosphoenolpyruvate carboxykinase or ferroactivator activity? Diabetes. 1985 Mar;34(3):246–250. doi: 10.2337/diab.34.3.246. [DOI] [PubMed] [Google Scholar]
  112. MacDonald M. J., Efendić S., Ostenson C. G. Normalization by insulin treatment of low mitochondrial glycerol phosphate dehydrogenase and pyruvate carboxylase in pancreatic islets of the GK rat. Diabetes. 1996 Jul;45(7):886–890. doi: 10.2337/diab.45.7.886. [DOI] [PubMed] [Google Scholar]
  113. MacDonald M. J. Elusive proximal signals of beta-cells for insulin secretion. Diabetes. 1990 Dec;39(12):1461–1466. doi: 10.2337/diab.39.12.1461. [DOI] [PubMed] [Google Scholar]
  114. MacDonald M. J. Feasibility of a mitochondrial pyruvate malate shuttle in pancreatic islets. Further implication of cytosolic NADPH in insulin secretion. J Biol Chem. 1995 Aug 25;270(34):20051–20058. [PubMed] [Google Scholar]
  115. MacDonald M. J. High content of mitochondrial glycerol-3-phosphate dehydrogenase in pancreatic islets and its inhibition by diazoxide. J Biol Chem. 1981 Aug 25;256(16):8287–8290. [PubMed] [Google Scholar]
  116. MacDonald M. J. Influence of glucose on pyruvate carboxylase expression in pancreatic islets. Arch Biochem Biophys. 1995 May 10;319(1):128–132. doi: 10.1006/abbi.1995.1274. [DOI] [PubMed] [Google Scholar]
  117. MacDonald M. J., Kaysen J. H., Moran S. M., Pomije C. E. Pyruvate dehydrogenase and pyruvate carboxylase. Sites of pretranslational regulation by glucose of glucose-induced insulin release in pancreatic islets. J Biol Chem. 1991 Nov 25;266(33):22392–22397. [PubMed] [Google Scholar]
  118. MacDonald M. J., McKenzie D. I., Walker T. M., Kaysen J. H. Lack of glyconeogenesis in pancreatic islets: expression of gluconeogenic enzyme genes in islets. Horm Metab Res. 1992 Apr;24(4):158–160. doi: 10.1055/s-2007-1003284. [DOI] [PubMed] [Google Scholar]
  119. MacKay N., Rigat B., Douglas C., Chen H. S., Robinson B. H. cDNA cloning of human kidney pyruvate carboxylase. Biochem Biophys Res Commun. 1994 Jul 29;202(2):1009–1014. doi: 10.1006/bbrc.1994.2029. [DOI] [PubMed] [Google Scholar]
  120. Mackall J. C., Lane M. D. Role of pyruvate carboxylase in fatty acid synthesis: alterations during preadipocyte differentiation. Biochem Biophys Res Commun. 1977 Dec 7;79(3):720–725. doi: 10.1016/0006-291x(77)91171-8. [DOI] [PubMed] [Google Scholar]
  121. Maloy W. L., Bowien B. U., Zwolinski G. K., Kumar K. G., Wood H. G., Ericsson L. H., Walsh K. A. Amino acid sequence of the biotinyl subunit from transcarboxylase. J Biol Chem. 1979 Nov 25;254(22):11615–11622. [PubMed] [Google Scholar]
  122. Martin A. D., Allan E. H., Titheradge M. A. The stimulation of mitochondrial pyruvate carboxylation after dexamethasone treatment of rats. Biochem J. 1984 Apr 1;219(1):107–115. doi: 10.1042/bj2190107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. Mayer F., Wallace J. C., Keech D. B. Further electron microscope studies on pyruvate carboxylase. Eur J Biochem. 1980 Nov;112(2):265–272. doi: 10.1111/j.1432-1033.1980.tb07202.x. [DOI] [PubMed] [Google Scholar]
  124. McAllister H. C., Coon M. J. Further studies on the properties of liver propionyl coenzyme A holocarboxylase synthetase and the specificity of holocarboxylase formation. J Biol Chem. 1966 Jun 25;241(12):2855–2861. [PubMed] [Google Scholar]
  125. McClure W. R., Lardy H. A., Cleland W. W. Rat liver pyruvate carboxylase. 3. Isotopic exchange studies of the first partial reaction. J Biol Chem. 1971 Jun 10;246(11):3584–3590. [PubMed] [Google Scholar]
  126. McCormack J. G., Halestrap A. P., Denton R. M. Role of calcium ions in regulation of mammalian intramitochondrial metabolism. Physiol Rev. 1990 Apr;70(2):391–425. doi: 10.1152/physrev.1990.70.2.391. [DOI] [PubMed] [Google Scholar]
  127. McKenna M. C., Tildon J. T., Stevenson J. H., Huang X. New insights into the compartmentation of glutamate and glutamine in cultured rat brain astrocytes. Dev Neurosci. 1996;18(5-6):380–390. doi: 10.1159/000111431. [DOI] [PubMed] [Google Scholar]
  128. Menéndez J., Delgado J., Gancedo C. Isolation of the Pichia pastoris PYC1 gene encoding pyruvate carboxylase and identification of a suppressor of the pyc phenotype. Yeast. 1998 May;14(7):647–654. doi: 10.1002/(SICI)1097-0061(199805)14:7<647::AID-YEA269>3.0.CO;2-L. [DOI] [PubMed] [Google Scholar]
  129. Menéndez J., Gancedo C. Regulatory regions in the promoters of the Saccharomyces cerevisiae PYC1 and PYC2 genes encoding isoenzymes of pyruvate carboxylase. FEMS Microbiol Lett. 1998 Jul 15;164(2):345–352. doi: 10.1111/j.1574-6968.1998.tb13108.x. [DOI] [PubMed] [Google Scholar]
  130. Merritt E. A., Murphy M. E. Raster3D Version 2.0. A program for photorealistic molecular graphics. Acta Crystallogr D Biol Crystallogr. 1994 Nov 1;50(Pt 6):869–873. doi: 10.1107/S0907444994006396. [DOI] [PubMed] [Google Scholar]
  131. Middleditch C., Clottes E., Burchell A. A different isoform of the transport protein mutated in the glycogen storage disease 1b is expressed in brain. FEBS Lett. 1998 Aug 14;433(1-2):33–36. doi: 10.1016/s0014-5793(98)00878-3. [DOI] [PubMed] [Google Scholar]
  132. Mitchell G. A., Robert M. F., Hruz P. W., Wang S., Fontaine G., Behnke C. E., Mende-Mueller L. M., Schappert K., Lee C., Gibson K. M. 3-Hydroxy-3-methylglutaryl coenzyme A lyase (HL). Cloning of human and chicken liver HL cDNAs and characterization of a mutation causing human HL deficiency. J Biol Chem. 1993 Feb 25;268(6):4376–4381. [PubMed] [Google Scholar]
  133. Moss J., Lane M. D. The biotin-dependent enzymes. Adv Enzymol Relat Areas Mol Biol. 1971;35:321–442. doi: 10.1002/9780470122808.ch7. [DOI] [PubMed] [Google Scholar]
  134. Mukhopadhyay B., Stoddard S. F., Wolfe R. S. Purification, regulation, and molecular and biochemical characterization of pyruvate carboxylase from Methanobacterium thermoautotrophicum strain deltaH. J Biol Chem. 1998 Feb 27;273(9):5155–5166. doi: 10.1074/jbc.273.9.5155. [DOI] [PubMed] [Google Scholar]
  135. Nyunoya H., Lusty C. J. The carB gene of Escherichia coli: a duplicated gene coding for the large subunit of carbamoyl-phosphate synthetase. Proc Natl Acad Sci U S A. 1983 Aug;80(15):4629–4633. doi: 10.1073/pnas.80.15.4629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  136. Ohneda M., Johnson J. H., Inman L. R., Chen L., Suzuki K., Goto Y., Alam T., Ravazzola M., Orci L., Unger R. H. GLUT2 expression and function in beta-cells of GK rats with NIDDM. Dissociation between reductions in glucose transport and glucose-stimulated insulin secretion. Diabetes. 1993 Jul;42(7):1065–1072. doi: 10.2337/diab.42.7.1065. [DOI] [PubMed] [Google Scholar]
  137. Osmani S. A., Mayer F., Marston F. A., Selmes I. P., Scrutton M. C. Pyruvate carboxylase from Aspergillus nidulans. Effects of regulatory modifiers on the structure of the enzyme. Eur J Biochem. 1984 Mar 15;139(3):509–518. doi: 10.1111/j.1432-1033.1984.tb08035.x. [DOI] [PubMed] [Google Scholar]
  138. Osmani S. A., Scrutton M. C., Mayer F. The structure and regulation of fungal pyruvate carboxylases. Ann N Y Acad Sci. 1985;447:56–71. doi: 10.1111/j.1749-6632.1985.tb18425.x. [DOI] [PubMed] [Google Scholar]
  139. Owen M. R., Halestrap A. P. The mechanisms by which mild respiratory chain inhibitors inhibit hepatic gluconeogenesis. Biochim Biophys Acta. 1993 Apr 5;1142(1-2):11–22. doi: 10.1016/0005-2728(93)90079-u. [DOI] [PubMed] [Google Scholar]
  140. Palmer J. D., Logsdon J. M., Jr The recent origins of introns. Curr Opin Genet Dev. 1991 Dec;1(4):470–477. doi: 10.1016/s0959-437x(05)80194-7. [DOI] [PubMed] [Google Scholar]
  141. Phillips N. F., Snoswell M. A., Chapman-Smith A., Keech D. B., Wallace J. C. Isolation of a carboxyphosphate intermediate and the locus of acetyl-CoA action in the pyruvate carboxylase reaction. Biochemistry. 1992 Oct 6;31(39):9445–9450. doi: 10.1021/bi00154a017. [DOI] [PubMed] [Google Scholar]
  142. Polakis S. E., Guchhait R. B., Zwergel E. E., Lane M. D., Cooper T. G. Acetyl coenzyme A carboxylase system of Escherichia coli. Studies on the mechanisms of the biotin carboxylase- and carboxyltransferase-catalyzed reactions. J Biol Chem. 1974 Oct 25;249(20):6657–6667. [PubMed] [Google Scholar]
  143. Pryor H. J., Smyth J. E., Quinlan P. T., Halestrap A. P. Evidence that the flux control coefficient of the respiratory chain is high during gluconeogenesis from lactate in hepatocytes from starved rats. Implications for the hormonal control of gluconeogenesis and action of hypoglycaemic agents. Biochem J. 1987 Oct 15;247(2):449–457. doi: 10.1042/bj2470449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  144. Reche P., Li Y. L., Fuller C., Eichhorn K., Perham R. N. Selectivity of post-translational modification in biotinylated proteins: the carboxy carrier protein of the acetyl-CoA carboxylase of Escherichia coli. Biochem J. 1998 Feb 1;329(Pt 3):589–596. doi: 10.1042/bj3290589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  145. Reddy D. V., Rothemund S., Shenoy B. C., Carey P. R., Sönnichsen F. D. Structural characterization of the entire 1.3S subunit of transcarboxylase from Propionibacterium shermanii. Protein Sci. 1998 Oct;7(10):2156–2163. doi: 10.1002/pro.5560071013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  146. Reed G. H., Scrutton M. C. Pyruvate carboxylase from chicken liver. Magnetic resonance studies of the effect of substrates and inhibitors on the environment of the bound manganese. J Biol Chem. 1974 Oct 10;249(19):6156–6162. [PubMed] [Google Scholar]
  147. Rinard G. A., Okuno G., Haynes R. C., Jr Stimulation of gluconeogenesis in rat liver slices by epinephrine and glucocorticoids. Endocrinology. 1969 Mar;84(3):622–631. doi: 10.1210/endo-84-3-622. [DOI] [PubMed] [Google Scholar]
  148. Robinson B. H., MacKay N., Chun K., Ling M. Disorders of pyruvate carboxylase and the pyruvate dehydrogenase complex. J Inherit Metab Dis. 1996;19(4):452–462. doi: 10.1007/BF01799106. [DOI] [PubMed] [Google Scholar]
  149. Robinson B. H., Oei J., Saudubray J. M., Marsac C., Bartlett K., Quan F., Gravel R. The French and North American phenotypes of pyruvate carboxylase deficiency, correlation with biotin containing protein by 3H-biotin incorporation, 35S-streptavidin labeling, and Northern blotting with a cloned cDNA probe. Am J Hum Genet. 1987 Jan;40(1):50–59. [PMC free article] [PubMed] [Google Scholar]
  150. Robinson B. H., Oei J., Saunders M., Gravel R. [3H]biotin-labeled proteins in cultured human skin fibroblasts from patients with pyruvate carboxylase deficiency. J Biol Chem. 1983 May 25;258(10):6660–6664. [PubMed] [Google Scholar]
  151. Rohde M., Lim F., Wallace J. C. Electron microscopic localization of pyruvate carboxylase in rat liver and Saccharomyces cerevisiae by immunogold procedures. Arch Biochem Biophys. 1991 Oct;290(1):197–201. doi: 10.1016/0003-9861(91)90608-l. [DOI] [PubMed] [Google Scholar]
  152. Rohde M., Lim F., Wallace J. C. Pyruvate carboxylase from Saccharomyces cerevisiae. Quaternary structure, effects of allosteric ligands and binding of avidin. Eur J Biochem. 1986 Apr 1;156(1):15–22. doi: 10.1111/j.1432-1033.1986.tb09542.x. [DOI] [PubMed] [Google Scholar]
  153. Rothman D. L., Magnusson I., Katz L. D., Shulman R. G., Shulman G. I. Quantitation of hepatic glycogenolysis and gluconeogenesis in fasting humans with 13C NMR. Science. 1991 Oct 25;254(5031):573–576. doi: 10.1126/science.1948033. [DOI] [PubMed] [Google Scholar]
  154. SEUBERT W., REMBERGER U. [Purification and mechanism of action of pyruvate carboxylase from Pseudomonas citronellolis]. Biochem Z. 1961;334:401–414. [PubMed] [Google Scholar]
  155. Salto R., Sola M., Oliver F. J., Vargas A. M. Effects of starvation, diabetes and carbon tetrachloride intoxication on rat kidney cortex and liver pyruvate carboxylase levels. Arch Physiol Biochem. 1996 Dec;104(7):845–850. doi: 10.1076/apab.104.7.845.13111. [DOI] [PubMed] [Google Scholar]
  156. Samols D., Thornton C. G., Murtif V. L., Kumar G. K., Haase F. C., Wood H. G. Evolutionary conservation among biotin enzymes. J Biol Chem. 1988 May 15;263(14):6461–6464. [PubMed] [Google Scholar]
  157. Schmoll D., Führmann E., Gebhardt R., Hamprecht B. Significant amounts of glycogen are synthesized from 3-carbon compounds in astroglial primary cultures from mice with participation of the mitochondrial phosphoenolpyruvate carboxykinase isoenzyme. Eur J Biochem. 1995 Jan 15;227(1-2):308–315. doi: 10.1111/j.1432-1033.1995.tb20390.x. [DOI] [PubMed] [Google Scholar]
  158. Schuit F., De Vos A., Farfari S., Moens K., Pipeleers D., Brun T., Prentki M. Metabolic fate of glucose in purified islet cells. Glucose-regulated anaplerosis in beta cells. J Biol Chem. 1997 Jul 25;272(30):18572–18579. doi: 10.1074/jbc.272.30.18572. [DOI] [PubMed] [Google Scholar]
  159. Schwarz E., Oesterhelt D., Reinke H., Beyreuther K., Dimroth P. The sodium ion translocating oxalacetate decarboxylase of Klebsiella pneumoniae. Sequence of the biotin-containing alpha-subunit and relationship to other biotin-containing enzymes. J Biol Chem. 1988 Jul 15;263(20):9640–9645. [PubMed] [Google Scholar]
  160. Scrutton M. C., Griminger P., Wallace J. C. Pyruvate carboxylase. Bound metal content of the vertebrate liver enzyme as a function of diet and species. J Biol Chem. 1972 May 25;247(10):3305–3313. [PubMed] [Google Scholar]
  161. Scrutton M. C., Taylor B. L. Isolation and characterization of pyruvate carboxylase from Azotobacter vinelandii OP. Arch Biochem Biophys. 1974 Oct;164(2):641–654. doi: 10.1016/0003-9861(74)90076-9. [DOI] [PubMed] [Google Scholar]
  162. Scrutton M. C., White M. D. Prufication and properties of human liver pyruvate carboxylase. Biochem Med. 1974 Mar;9(3):217–292. doi: 10.1016/0006-2944(74)90062-3. [DOI] [PubMed] [Google Scholar]
  163. Scrutton M. C., White M. D. Pyruvate carboxylase. Specific inactivation of acetyl coenzyme A-dependent oxylacetate synthesis during modification of the enzyme by trinitrobenzene sulfonate. J Biol Chem. 1973 Aug 10;248(15):5541–5544. [PubMed] [Google Scholar]
  164. Scrutton M. C., Young M. R., Utter M. F. Pyruvate carboxylase from baker's yeast. The presence of bound zinc. J Biol Chem. 1970 Nov 25;245(22):6220–6227. [PubMed] [Google Scholar]
  165. Seitz H. J., Kaiser M., Krone W., Tarnowski W. Physiologic significance of glucocorticoids and insulin in the regulation of hepatic gluconeogenesis during starvation in rats. Metabolism. 1976 Dec;25(12):1545–1555. doi: 10.1016/0026-0495(76)90107-4. [DOI] [PubMed] [Google Scholar]
  166. Sekine N., Cirulli V., Regazzi R., Brown L. J., Gine E., Tamarit-Rodriguez J., Girotti M., Marie S., MacDonald M. J., Wollheim C. B. Low lactate dehydrogenase and high mitochondrial glycerol phosphate dehydrogenase in pancreatic beta-cells. Potential role in nutrient sensing. J Biol Chem. 1994 Feb 18;269(7):4895–4902. [PubMed] [Google Scholar]
  167. Shank R. P., Leo G. C., Zielke H. R. Cerebral metabolic compartmentation as revealed by nuclear magnetic resonance analysis of D-[1-13C]glucose metabolism. J Neurochem. 1993 Jul;61(1):315–323. doi: 10.1111/j.1471-4159.1993.tb03570.x. [DOI] [PubMed] [Google Scholar]
  168. Shenoy B. C., Paranjape S., Murtif V. L., Kumar G. K., Samols D., Wood H. G. Effect of mutations at Met-88 and Met-90 on the biotination of Lys-89 of the apo 1.3S subunit of transcarboxylase. FASEB J. 1988 Jun;2(9):2505–2511. doi: 10.1096/fasebj.2.9.3131174. [DOI] [PubMed] [Google Scholar]
  169. Srere P. A. Complexes of sequential metabolic enzymes. Annu Rev Biochem. 1987;56:89–124. doi: 10.1146/annurev.bi.56.070187.000513. [DOI] [PubMed] [Google Scholar]
  170. Srivastava G., Borthwick I. A., Brooker J. D., Wallace J. C., May B. K., Elliott W. H. Hemin inhibits transfer of pre-delta-aminolevulinate synthase into chick embryo liver mitochondria. Biochem Biophys Res Commun. 1983 Nov 30;117(1):344–349. doi: 10.1016/0006-291x(83)91582-6. [DOI] [PubMed] [Google Scholar]
  171. Stapleton M. A., Javid-Majd F., Harmon M. F., Hanks B. A., Grahmann J. L., Mullins L. S., Raushel F. M. Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase. Biochemistry. 1996 Nov 12;35(45):14352–14361. doi: 10.1021/bi961183y. [DOI] [PubMed] [Google Scholar]
  172. Stucka R., Dequin S., Salmon J. M., Gancedo C. DNA sequences in chromosomes II and VII code for pyruvate carboxylase isoenzymes in Saccharomyces cerevisiae: analysis of pyruvate carboxylase-deficient strains. Mol Gen Genet. 1991 Oct;229(2):307–315. doi: 10.1007/BF00272171. [DOI] [PubMed] [Google Scholar]
  173. Student A. K., Hsu R. Y., Lane M. D. Induction of fatty acid synthetase synthesis in differentiating 3T3-L1 preadipocytes. J Biol Chem. 1980 May 25;255(10):4745–4750. [PubMed] [Google Scholar]
  174. Sundaram T. K., Cazzulo J. J., Kornberg H. L. Pyruvate holocarboxylase formation from the apoenzyme and D-biotin in Saccharomyces cerevisiae. Arch Biochem Biophys. 1971 Apr;143(2):609–616. doi: 10.1016/0003-9861(71)90246-3. [DOI] [PubMed] [Google Scholar]
  175. Söling H. D., Willms B., Kleineke J., Gehlhoff M. Regulation of gluconeogenesis in the guinea pig liver. Eur J Biochem. 1970 Oct;16(2):289–302. doi: 10.1111/j.1432-1033.1970.tb01084.x. [DOI] [PubMed] [Google Scholar]
  176. Taylor B. L., Frey W. H., 2nd, Barden R. E., Scrutton M. C., Utter M. F. The use of the ultracentrifuge to determine the catalytically competent forms of enzymes with more than one oligomeric structure. Multiple reacting forms of pyruvate carboxylase from chicken and rat liver. J Biol Chem. 1978 May 10;253(9):3062–3069. [PubMed] [Google Scholar]
  177. Taylor P. H., Wallace J. C., Keech D. B. Gluconeogenic enzymes in sheep liver. Intracellular localization of pyruvate carboxylase and phosphoenolpyruvate carboxykinase in normal, fasted and diabetic sheep. Biochim Biophys Acta. 1971 May 18;237(2):179–191. [PubMed] [Google Scholar]
  178. Thoden J. B., Holden H. M., Wesenberg G., Raushel F. M., Rayment I. Structure of carbamoyl phosphate synthetase: a journey of 96 A from substrate to product. Biochemistry. 1997 May 27;36(21):6305–6316. doi: 10.1021/bi970503q. [DOI] [PubMed] [Google Scholar]
  179. Thomas A. P., Halestrap A. P. Computer stimulation of the effects of alpha-cyano-4-hydroxycinnamate on gluconeogenesis from L-lactate in rat liver cells. Biochem J. 1981 Sep 15;198(3):561–564. doi: 10.1042/bj1980561. [DOI] [PMC free article] [PubMed] [Google Scholar]
  180. Thompson J. D., Higgins D. G., Gibson T. J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 1994 Nov 11;22(22):4673–4680. doi: 10.1093/nar/22.22.4673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  181. Thornton C. G., Kumar G. K., Shenoy B. C., Haase F. C., Phillips N. F., Park V. M., Magner W. J., Hejlik D. P., Wood H. G., Samols D. Primary structure of the 5 S subunit of transcarboxylase as deduced from the genomic DNA sequence. FEBS Lett. 1993 Sep 13;330(2):191–196. doi: 10.1016/0014-5793(93)80271-u. [DOI] [PubMed] [Google Scholar]
  182. Tipton P. A., Cleland W. W. Catalytic mechanism of biotin carboxylase: steady-state kinetic investigations. Biochemistry. 1988 Jun 14;27(12):4317–4325. doi: 10.1021/bi00412a019. [DOI] [PubMed] [Google Scholar]
  183. Tu Z., Hagedorn H. H. Biochemical, molecular, and phylogenetic analysis of pyruvate carboxylase in the yellow fever mosquito, Aedes aegypti. Insect Biochem Mol Biol. 1997 Feb;27(2):133–147. doi: 10.1016/s0965-1748(96)00078-1. [DOI] [PubMed] [Google Scholar]
  184. UTTER M. F., KEECH D. B. PYRUVATE CARBOXYLASE. I. NATURE OF THE REACTION. J Biol Chem. 1963 Aug;238:2603–2608. [PubMed] [Google Scholar]
  185. Val D. L., Chapman-Smith A., Walker M. E., Cronan J. E., Jr, Wallace J. C. Polymorphism of the yeast pyruvate carboxylase 2 gene and protein: effects on protein biotinylation. Biochem J. 1995 Dec 15;312(Pt 3):817–825. doi: 10.1042/bj3120817. [DOI] [PMC free article] [PubMed] [Google Scholar]
  186. Vallee B. L., Auld D. S. Zinc coordination, function, and structure of zinc enzymes and other proteins. Biochemistry. 1990 Jun 19;29(24):5647–5659. doi: 10.1021/bi00476a001. [DOI] [PubMed] [Google Scholar]
  187. Waldrop G. L., Rayment I., Holden H. M. Three-dimensional structure of the biotin carboxylase subunit of acetyl-CoA carboxylase. Biochemistry. 1994 Aug 30;33(34):10249–10256. doi: 10.1021/bi00200a004. [DOI] [PubMed] [Google Scholar]
  188. Walker M. E., Baker E., Wallace J. C., Sutherland G. R. Assignment of the human pyruvate carboxylase gene (PC) to 11q13.4 by fluorescence in situ hybridisation. Cytogenet Cell Genet. 1995;69(3-4):187–189. doi: 10.1159/000133958. [DOI] [PubMed] [Google Scholar]
  189. Walker M. E., Val D. L., Rohde M., Devenish R. J., Wallace J. C. Yeast pyruvate carboxylase: identification of two genes encoding isoenzymes. Biochem Biophys Res Commun. 1991 May 15;176(3):1210–1217. doi: 10.1016/0006-291x(91)90414-3. [DOI] [PubMed] [Google Scholar]
  190. Walker M. E., Wallace J. C. Isolation of a yeast mutant deficient in pyruvate carboxylase activity. Biochem Int. 1991 Mar;23(4):697–705. [PubMed] [Google Scholar]
  191. Wallace J. C., Jitrapakdee S., Chapman-Smith A. Pyruvate carboxylase. Int J Biochem Cell Biol. 1998 Jan;30(1):1–5. doi: 10.1016/s1357-2725(97)00147-7. [DOI] [PubMed] [Google Scholar]
  192. Webb G. C., Jitrapakdee S., Bottema C. D., Wallace J. C. Assignment of the pyruvate carboxylase gene to rat chromosome band 1q43 by in situ hybridization. Cytogenet Cell Genet. 1997;79(1-2):151–152. doi: 10.1159/000134707. [DOI] [PubMed] [Google Scholar]
  193. Weinberg M. B., Utter M. F. Effect of streptozotocin-induced diabetes mellitus on the turnover of rat liver pyruvate carboxylase and pyruvate dehydrogenase. Biochem J. 1980 Jun 15;188(3):601–608. doi: 10.1042/bj1880601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  194. Weinberg M. B., Utter M. F. Effect of thyroid hormone on the turnover of rat liver pyruvate carboxylase and pyruvate dehydrogenase. J Biol Chem. 1979 Oct 10;254(19):9492–9499. [PubMed] [Google Scholar]
  195. Werneburg B. G., Ash D. E. Chemical modifications of chicken liver pyruvate carboxylase: evidence for essential cysteine-lysine pairs and a reactive sulfhydryl group. Arch Biochem Biophys. 1993 Jun;303(2):214–221. doi: 10.1006/abbi.1993.1275. [DOI] [PubMed] [Google Scholar]
  196. Werneburg B. G., Ash D. E. VO2+(IV) complexes with pyruvate carboxylase: activation of oxaloacetate decarboxylation and EPR properties of enzyme-VO2+ complexes. Biochemistry. 1997 Nov 25;36(47):14392–14402. doi: 10.1021/bi971282r. [DOI] [PubMed] [Google Scholar]
  197. Wexler I. D., Du Y., Lisgaris M. V., Mandal S. K., Freytag S. O., Yang B. S., Liu T. C., Kwon M., Patel M. S., Kerr D. S. Primary amino acid sequence and structure of human pyruvate carboxylase. Biochim Biophys Acta. 1994 Oct 21;1227(1-2):46–52. doi: 10.1016/0925-4439(94)90105-8. [DOI] [PubMed] [Google Scholar]
  198. Wexler I. D., Kerr D. S., Du Y., Kaung M. M., Stephenson W., Lusk M. M., Wappner R. S., Higgins J. J. Molecular characterization of pyruvate carboxylase deficiency in two consanguineous families. Pediatr Res. 1998 May;43(5):579–584. doi: 10.1203/00006450-199805000-00004. [DOI] [PubMed] [Google Scholar]
  199. White M. F., Kahn C. R. The insulin signaling system. J Biol Chem. 1994 Jan 7;269(1):1–4. [PubMed] [Google Scholar]
  200. Wiesinger H., Hamprecht B., Dringen R. Metabolic pathways for glucose in astrocytes. Glia. 1997 Sep;21(1):22–34. doi: 10.1002/(sici)1098-1136(199709)21:1<22::aid-glia3>3.0.co;2-3. [DOI] [PubMed] [Google Scholar]
  201. Wimhurst J. M., Manchester K. L. A comparison of the effects of diabetes induced with either alloxan or streptozotocin and of starvation on the activities in rat liver of the key enzymes of gluconeogenesis. Biochem J. 1970 Nov;120(1):95–103. doi: 10.1042/bj1200095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  202. Woehlke G., Wifling K., Dimroth P. Sequence of the sodium ion pump oxaloacetate decarboxylase from Salmonella typhimurium. J Biol Chem. 1992 Nov 15;267(32):22798–22803. [PubMed] [Google Scholar]
  203. Wolodko W. T., Fraser M. E., James M. N., Bridger W. A. The crystal structure of succinyl-CoA synthetase from Escherichia coli at 2.5-A resolution. J Biol Chem. 1994 Apr 8;269(14):10883–10890. doi: 10.2210/pdb1scu/pdb. [DOI] [PubMed] [Google Scholar]
  204. Wood H. G., Barden R. E. Biotin enzymes. Annu Rev Biochem. 1977;46:385–413. doi: 10.1146/annurev.bi.46.070177.002125. [DOI] [PubMed] [Google Scholar]
  205. Wurtele E. S., Nikolau B. J. Plants contain multiple biotin enzymes: discovery of 3-methylcrotonyl-CoA carboxylase, propionyl-CoA carboxylase and pyruvate carboxylase in the plant kingdom. Arch Biochem Biophys. 1990 Apr;278(1):179–186. doi: 10.1016/0003-9861(90)90246-u. [DOI] [PubMed] [Google Scholar]
  206. Yakunin A. F., Hallenbeck P. C. Regulation of synthesis of pyruvate carboxylase in the photosynthetic bacterium Rhodobacter capsulatus. J Bacteriol. 1997 Mar;179(5):1460–1468. doi: 10.1128/jb.179.5.1460-1468.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  207. Yamaguchi H., Kato H., Hata Y., Nishioka T., Kimura A., Oda J., Katsube Y. Three-dimensional structure of the glutathione synthetase from Escherichia coli B at 2.0 A resolution. J Mol Biol. 1993 Feb 20;229(4):1083–1100. doi: 10.1006/jmbi.1993.1106. [DOI] [PubMed] [Google Scholar]
  208. Yao X., Wei D., Soden C., Jr, Summers M. F., Beckett D. Structure of the carboxy-terminal fragment of the apo-biotin carboxyl carrier subunit of Escherichia coli acetyl-CoA carboxylase. Biochemistry. 1997 Dec 9;36(49):15089–15100. doi: 10.1021/bi971485f. [DOI] [PubMed] [Google Scholar]
  209. Yeung D., Stanley R. S., Oliver I. T. Development of gluconeogenesis in neonatal rat liver. Effect of triamcinolone. Biochem J. 1967 Dec;105(3):1219–1227. doi: 10.1042/bj1051219. [DOI] [PMC free article] [PubMed] [Google Scholar]
  210. Zempleni J., Trusty T. A., Mock D. M. Lipoic acid reduces the activities of biotin-dependent carboxylases in rat liver. J Nutr. 1997 Sep;127(9):1776–1781. doi: 10.1093/jn/127.9.1776. [DOI] [PubMed] [Google Scholar]
  211. Zhang J., Xia W. L., Ahmad F. Regulation of pyruvate carboxylase in 3T3-L1 cells. Biochem J. 1995 Feb 15;306(Pt 1):205–210. doi: 10.1042/bj3060205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  212. Zhang J., Xia W. L., Brew K., Ahmad F. Adipose pyruvate carboxylase: amino acid sequence and domain structure deduced from cDNA sequencing. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1766–1770. doi: 10.1073/pnas.90.5.1766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  213. Zimmer D. B., Magnuson M. A. Immunohistochemical localization of phosphoenolpyruvate carboxykinase in adult and developing mouse tissues. J Histochem Cytochem. 1990 Feb;38(2):171–178. doi: 10.1177/38.2.1688895. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES