Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1998 Jul 15;333(Pt 2):359–366. doi: 10.1042/bj3330359

Human mitochondrial phosphoenolpyruvate carboxykinase 2 gene. Structure, chromosomal localization and tissue-specific expression.

S Modaressi 1, K Brechtel 1, B Christ 1, K Jungermann 1
PMCID: PMC1219593  PMID: 9657976

Abstract

The mitochodrial (mt) phosphoenolpyruvate carboxykinase 2 (PCK2) gene was isolated by screening a human genomic library with a rat cytosolic (cy) PCK1 cDNA probe comprising sequences from exons 2-9 and by PCR amplification of human genomic DNA spanning consecutive exons with known primer pairs from mtPCK2 cDNA containing sequences from two putative neighbouring exons. The mtPCK2 gene spans approx. 10 kb and consists of ten exons and nine introns. All exon-intron junction sequences match the classical GT/AG rule. Northern blot analysis of poly(A)+ and total RNA from various tissues revealed one mRNA species of approx. 2.4 kb. The gene is expressed in a variety of human tissues, mainly in liver, kidney, pancreas, intestine and fibroblasts. In contrast with the cytosolic isoenzyme, the mitochondrial form might not have a purely gluconeogenic function. The mtPCK2 gene maps to chromosome 14q11.2-q12, in contrast with the cyPCK1 gene located on 20q13.2-q13.31.

Full Text

The Full Text of this article is available as a PDF (1.8 MB).

Selected References

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

  1. Andersen B., Nath A., Jungermann K. Heterogeneous distribution of phosphoenolpyruvate carboxykinase in rat liver parenchyma, isolated, and cultured hepatocytes. Eur J Cell Biol. 1982 Aug;28(1):47–53. [PubMed] [Google Scholar]
  2. Ballard F. J., Hanson R. W. Purification of phosphoenolpyruvate carboxykinase from the cytosol fraction of rat liver and the immunochemical demonstration of differences between this enzyme and the mitochondrial phosphoenolpyruvate carboxykinase. J Biol Chem. 1969 Oct 25;244(20):5625–5630. [PubMed] [Google Scholar]
  3. Bartels H., Freimann S., Jungermann K. Predominant periportal expression of the phosphoenolpyruvate carboxykinase gene in liver of fed and fasted mice, hamsters and rats studied by in situ hybridization. Histochemistry. 1993 Apr;99(4):303–309. doi: 10.1007/BF00269103. [DOI] [PubMed] [Google Scholar]
  4. Bartels H., Herbort H., Jungermann K. Predominant periportal expression of the phosphoenolpyruvate carboxykinase and tyrosine aminotransferase genes in rat liver. Dynamics during the daily feeding rhythm and starvation-refeeding cycle demonstrated by in situ hybridization. Histochemistry. 1990;94(6):637–644. doi: 10.1007/BF00271991. [DOI] [PubMed] [Google Scholar]
  5. Bartels H., Linnemann H., Jungermann K. Predominant localization of phosphoenolpyruvate carboxykinase mRNA in the periportal zone of rat liver parenchyma demonstrated by in situ hybridization. FEBS Lett. 1989 May 8;248(1-2):188–194. doi: 10.1016/0014-5793(89)80459-4. [DOI] [PubMed] [Google Scholar]
  6. Beale E. G., Chrapkiewicz N. B., Scoble H. A., Metz R. J., Quick D. P., Noble R. L., Donelson J. E., Biemann K., Granner D. K. Rat hepatic cytosolic phosphoenolpyruvate carboxykinase (GTP). Structures of the protein, messenger RNA, and gene. J Biol Chem. 1985 Sep 5;260(19):10748–10760. [PubMed] [Google Scholar]
  7. Brech W., Shrago E., Wilken D. Studies on pyruvate carboxylase in rat and human liver. Biochim Biophys Acta. 1970 Feb 24;201(2):145–154. doi: 10.1016/0304-4165(70)90288-6. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Clayton P. T., Hyland K., Brand M., Leonard J. V. Mitochondrial phosphoenolpyruvate carboxykinase deficiency. Eur J Pediatr. 1986 Apr;145(1-2):46–50. doi: 10.1007/BF00441851. [DOI] [PubMed] [Google Scholar]
  10. Cook J. S., Weldon S. L., Garcia-Ruiz J. P., Hod Y., Hanson R. W. Nucleotide sequence of the mRNA encoding the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) from the chicken. Proc Natl Acad Sci U S A. 1986 Oct;83(20):7583–7587. doi: 10.1073/pnas.83.20.7583. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cornell N. W., Schramm V. L., Kerich M. J., Emig F. A. Subcellular location of phosphoenolpyruvate carboxykinase in hepatocytes from fed and starved rats. J Nutr. 1986 Jun;116(6):1101–1108. doi: 10.1093/jn/116.6.1101. [DOI] [PubMed] [Google Scholar]
  12. Elliott K. R., Pogson C. I. The effects of starvation and experimental diabetes on phosphoenol-pyruvate carboxykinase in the guinea pig. Biochem J. 1977 May 15;164(2):357–361. doi: 10.1042/bj1640357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fink T. M., Lichter P., Wekerle H., Zimmer M., Jenne D. E. The human granzyme A (HFSP, CTLA3) gene maps to 5q11-q12 and defines a new locus of the serine protease superfamily. Genomics. 1993 Nov;18(2):401–403. doi: 10.1006/geno.1993.1483. [DOI] [PubMed] [Google Scholar]
  14. Guder W. G., Schmidt U. Liver cell heterogeneity. The distribution of pyruvate kinase and phosphoenolpyruvate carboxykinase (GTP) in the liver lobule of fed and starved rats. Hoppe Seylers Z Physiol Chem. 1976 Dec;357(12):1793–1800. doi: 10.1515/bchm2.1976.357.2.1793. [DOI] [PubMed] [Google Scholar]
  15. Hod Y., Cook J. S., Weldon S. L., Short J. M., Wynshaw-Boris A., Hanson R. W. Differential expression of the genes for the mitochondrial and cytosolic forms of phosphoenolpyruvate carboxykinase. Ann N Y Acad Sci. 1986;478:31–45. doi: 10.1111/j.1749-6632.1986.tb15519.x. [DOI] [PubMed] [Google Scholar]
  16. Hod Y., Utter M. F., Hanson R. W. The mitochondrial and cytosolic forms of avian phosphoenolpyruvate carboxykinase (GTP) are encoded by different messenger RNAs. J Biol Chem. 1982 Nov 25;257(22):13787–13794. [PubMed] [Google Scholar]
  17. Hommes F. A., Bendien K., Elema J. D., Bremer H. J., Lombeck I. Two cases of phosphoenolpyruvate carboxykinase deficiency. Acta Paediatr Scand. 1976 Mar;65(2):233–240. doi: 10.1111/j.1651-2227.1976.tb16543.x. [DOI] [PubMed] [Google Scholar]
  18. Jurka J., Smith T. A fundamental division in the Alu family of repeated sequences. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4775–4778. doi: 10.1073/pnas.85.13.4775. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kietzmann T., Schmidt H., Unthan-Fechner K., Probst I., Jungermann K. A ferro-heme protein senses oxygen levels, which modulate the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in rat hepatocyte cultures. Biochem Biophys Res Commun. 1993 Sep 15;195(2):792–798. doi: 10.1006/bbrc.1993.2115. [DOI] [PubMed] [Google Scholar]
  20. Lamballe F., Klein R., Barbacid M. trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991 Sep 6;66(5):967–979. doi: 10.1016/0092-8674(91)90442-2. [DOI] [PubMed] [Google Scholar]
  21. Leonard J. V., Hyland K., Furukawa N., Clayton P. T. Mitochondrial phosphoenolpyruvate carboxykinase deficiency. Eur J Pediatr. 1991 Jan;150(3):198–199. doi: 10.1007/BF01963566. [DOI] [PubMed] [Google Scholar]
  22. Lichter P., Tang C. J., Call K., Hermanson G., Evans G. A., Housman D., Ward D. C. High-resolution mapping of human chromosome 11 by in situ hybridization with cosmid clones. Science. 1990 Jan 5;247(4938):64–69. doi: 10.1126/science.2294592. [DOI] [PubMed] [Google Scholar]
  23. Matsuo M., Maeda E., Nakamura H., Koike K., Koike M. Hepatic phosphoenolpyruvate carboxykinase deficiency: a neonatal case with reduced activity of pyruvate carboxylase. J Inherit Metab Dis. 1989;12(3):336–337. doi: 10.1007/BF01799232. [DOI] [PubMed] [Google Scholar]
  24. McGrane M. M., Yun J. S., Patel Y. M., Hanson R. W. Metabolic control of gene expression: in vivo studies with transgenic mice. Trends Biochem Sci. 1992 Jan;17(1):40–44. doi: 10.1016/0968-0004(92)90426-a. [DOI] [PubMed] [Google Scholar]
  25. Miller S. A., Dykes D. D., Polesky H. F. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988 Feb 11;16(3):1215–1215. doi: 10.1093/nar/16.3.1215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Modaressi S., Christ B., Bratke J., Zahn S., Heise T., Jungermann K. Molecular cloning, sequencing and expression of the cDNA of the mitochondrial form of phosphoenolpyruvate carboxykinase from human liver. Biochem J. 1996 May 1;315(Pt 3):807–814. doi: 10.1042/bj3150807. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. NORDLIE R. C., LARDY H. A. Mammalian liver phosphoneolpyruvate carboxykinase activities. J Biol Chem. 1963 Jul;238:2259–2263. [PubMed] [Google Scholar]
  28. Nolte J., Brdiczka D., Pette D. Intracellular distribution of phosphoenolpyruvate carboxylase and (NADP) malate dehydrogenase in different muscle types. Biochim Biophys Acta. 1972 Oct 12;284(2):497–507. doi: 10.1016/0005-2744(72)90148-9. [DOI] [PubMed] [Google Scholar]
  29. O'Brien R. M., Granner D. K. Regulation of gene expression by insulin. Physiol Rev. 1996 Oct;76(4):1109–1161. doi: 10.1152/physrev.1996.76.4.1109. [DOI] [PubMed] [Google Scholar]
  30. Pari G., Jardine K., McBurney M. W. Multiple CArG boxes in the human cardiac actin gene promoter required for expression in embryonic cardiac muscle cells developing in vitro from embryonal carcinoma cells. Mol Cell Biol. 1991 Sep;11(9):4796–4803. doi: 10.1128/mcb.11.9.4796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Runge D., Schmidt H., Christ B., Jungermann K. Mechanism of the permissive action of dexamethasone on the glucagon-dependent activation of the phosphoenolpyruvate carboxykinase gene in cultured rat hepatocytes. Eur J Biochem. 1991 Jun 15;198(3):641–649. doi: 10.1111/j.1432-1033.1991.tb16062.x. [DOI] [PubMed] [Google Scholar]
  32. SHRAGO E., LARDY H. A., NORDLIE R. C., FOSTER D. O. METABOLIC AND HORMONAL CONTROL OF PHOSPHOENOLPYRUVATE CARBOXYKINASE AND MALIC ENZYME IN RAT LIVER. J Biol Chem. 1963 Oct;238:3188–3192. [PubMed] [Google Scholar]
  33. Stoffel M., Xiang K. S., Espinosa R., 3rd, Cox N. J., Le Beau M. M., Bell G. I. cDNA sequence and localization of polymorphic human cytosolic phosphoenolpyruvate carboxykinase gene (PCK1) to chromosome 20, band q13.31: PCK1 is not tightly linked to maturity-onset diabetes of the young. Hum Mol Genet. 1993 Jan;2(1):1–4. doi: 10.1093/hmg/2.1.1. [DOI] [PubMed] [Google Scholar]
  34. Ting C. N., Burgess D. L., Chamberlain J. S., Keith T. P., Falls K., Meisler M. H. Phosphoenolpyruvate carboxykinase (GTP): characterization of the human PCK1 gene and localization distal to MODY on chromosome 20. Genomics. 1993 Jun;16(3):698–706. doi: 10.1006/geno.1993.1250. [DOI] [PubMed] [Google Scholar]
  35. UTTER M. F., KURAHASHI K. Purification of oxalacetic carboxylase from chicken liver. J Biol Chem. 1954 Apr;207(2):787–802. [PubMed] [Google Scholar]
  36. Vidnes J., Sovik O. Gluconeogenesis in infancy and childhood. III. Deficiency of the extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hypoglycaemia. Acta Paediatr Scand. 1976 May;65(3):307–312. doi: 10.1111/j.1651-2227.1976.tb04890.x. [DOI] [PubMed] [Google Scholar]
  37. Watford M., Hod Y., Chiao Y. B., Utter M. F., Hanson R. W. The unique role of the kidney in gluconeogenesis in the chicken. The significance of a cytosolic form of phosphoenolpyruvate carboxykinase. J Biol Chem. 1981 Oct 10;256(19):10023–10027. [PubMed] [Google Scholar]
  38. Weldon S. L., Rando A., Matathias A. S., Hod Y., Kalonick P. A., Savon S., Cook J. S., Hanson R. W. Mitochondrial phosphoenolpyruvate carboxykinase from the chicken. Comparison of the cDNA and protein sequences with the cytosolic isozyme. J Biol Chem. 1990 May 5;265(13):7308–7317. [PubMed] [Google Scholar]
  39. Wieland O., Evertz-Prüsse E., Stukowski B. Distribution of pyruvate carboxylase and phosphoenol-pyruvate carboxikinase in human liver. FEBS Lett. 1968 Nov;2(1):26–28. doi: 10.1016/0014-5793(68)80091-2. [DOI] [PubMed] [Google Scholar]

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

RESOURCES