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. 1980 Jan;141(1):235–245. doi: 10.1128/jb.141.1.235-245.1980

Regulation of phosphoglycerate dehydrogenase levels and effect on serine synthesis in Escherichia coli K-12.

J C McKitrick, L I Pizer
PMCID: PMC293570  PMID: 6986358

Abstract

The level of phosphoglycerate dehydrogenase, the first enzyme in the biosynthetic pathway to serine and glycine, has been studied in Escherichia coli grown under different conditions. The enzyme level was not reduced by growth in a medium which contained the end products of the pathway, nor was it elevated when the growth rates was limited by the supply of serine. Elevation of phosphoglycerate dehydrogenase did not occur when charging of tRNA ser was inhibited by serine hydroxamate. However, phosphoglycerate dehydrogenase levels were subject to regulation. Elevated levels of enzyme activity were observed in merodiploids containing multiple copies of the serA gene, and lowered enzyme levels were found in cells grown on carbon sources other than glucose or when certain amino acids were present in the growth medium. The combined effect of these nutritional changes (carbon source and amino acids) reduced the level of phosphoglycerate dehydrogenase to 10 to 12% of that found in wild-type cells and to about 5% of the level in the merodiploids. By using antibody prepared against purified phosphoglycerate dehydrogenase we established that the decrease in enzyme activity reflected decreased amounts of enzyme protein. Constant intracellular concentrations of 3-phosphoglycerate and serine were found in cells with marked differences in phosphoglycerate dehydrogenase activity, indicating that end product inhibition of phosphoglycerate dehydrogenase activity, rather than the amount of the biosynthetic enzymes, is the major factor in regulating the intracellular concentration of serine.

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Selected References

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

  1. BORKENHAGEN L. F., KENNEDY E. P. The enzymatic exchange of L-serine with O-phospho-L-serine catalyzed by a specific phosphatase. J Biol Chem. 1959 Apr;234(4):849–853. [PubMed] [Google Scholar]
  2. Buettner M. J., Spitz E., Rickenberg H. V. Cyclic adenosine 3',5'-monophosphate in Escherichia coli. J Bacteriol. 1973 Jun;114(3):1068–1073. doi: 10.1128/jb.114.3.1068-1073.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. D'Alessio G., Josse J. Glyceraldehyde phosphate dehydrogenase, phosphoglycerate kinase, and phosphoglyceromutase of Escherichia coli. Simultaneous purification and physical properties. J Biol Chem. 1971 Jul 10;246(13):4319–4325. [PubMed] [Google Scholar]
  4. Dempsey W. B. Evidence that 3-phosphoserine may be a precursor of vitamin B6 in Escherichia coli. Biochem Biophys Res Commun. 1969 Sep 24;37(1):89–93. [PubMed] [Google Scholar]
  5. Dempsey W. B., Ito H. Characterization of pyridoxine auxotrophs of Escherichia coli: serine and pdxF mutants. J Bacteriol. 1970 Nov;104(2):658–667. doi: 10.1128/jb.104.2.658-667.1970. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dubrow R., Pizer L. I. Transient kinetic and deuterium isotope effect studies on the catalytic mechanism of phosphoglycerate dehydrogenase. J Biol Chem. 1977 Mar 10;252(5):1539–1551. [PubMed] [Google Scholar]
  7. Dubrow R., Pizer L. I. Transient kinetic studies on the allosteric transition of phosphoglycerate dehydrogenase. J Biol Chem. 1977 Mar 10;252(5):1527–1538. [PubMed] [Google Scholar]
  8. Fraenkel D. G., Banerjee S. A mutation increasing the amount of a constitutive enzyme in Escherichia coli, glucose 6-phosphate dehydrogenase. J Mol Biol. 1971 Feb 28;56(1):183–194. doi: 10.1016/0022-2836(71)90093-3. [DOI] [PubMed] [Google Scholar]
  9. Fraenkel D. G., Levisohn S. R. Glucose and gluconate metabolism in an Escherichia coli mutant lacking phosphoglucose isomerase. J Bacteriol. 1967 May;93(5):1571–1578. doi: 10.1128/jb.93.5.1571-1578.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. GERHART J. C., PARDEE A. B. The enzymology of control by feedback inhibition. J Biol Chem. 1962 Mar;237:891–896. [PubMed] [Google Scholar]
  11. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  12. Lowry O. H., Carter J., Ward J. B., Glaser L. The effect of carbon and nitrogen sources on the level of metabolic intermediates in Escherichia coli. J Biol Chem. 1971 Nov;246(21):6511–6521. [PubMed] [Google Scholar]
  13. PIZER L. I. ENZYMOLOGY AND REGULATION OF SERINE BIOSYNTHESIS IN CULTURED HUMAN CELLS. J Biol Chem. 1964 Dec;239:4219–4226. [PubMed] [Google Scholar]
  14. PIZER L. I., POTOCHNY M. L. NUTRITIONAL AND REGULATORY ASPECTS OF SERINE METABOLISM IN ESCHERICHIA COLI. J Bacteriol. 1964 Sep;88:611–619. doi: 10.1128/jb.88.3.611-619.1964. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. PIZER L. I. THE PATHWAY AND CONTROL OF SERINE BIOSYNTHESIS IN ESCHERICHIA COLI. J Biol Chem. 1963 Dec;238:3934–3944. [PubMed] [Google Scholar]
  16. Perlman R. L., De Crombrugghe B., Pastan I. Cyclic AMP regulates catabolite and transient repression in E. coli. Nature. 1969 Aug 23;223(5208):810–812. doi: 10.1038/223810a0. [DOI] [PubMed] [Google Scholar]
  17. Prusiner S., Miller R. E., Valentine R. C. Adenosine 3':5'-cyclic monophosphate control of the enzymes of glutamine metabolism in Escherichia coli. Proc Natl Acad Sci U S A. 1972 Oct;69(10):2922–2926. doi: 10.1073/pnas.69.10.2922. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Rose J. K., Yanofsky C. Metabolic regulation of the tryptophan operon of Escherichia coli: repressor-independent regulation of transcription initiation frequency. J Mol Biol. 1972 Aug 14;69(1):103–118. doi: 10.1016/0022-2836(72)90026-5. [DOI] [PubMed] [Google Scholar]
  19. Roth J. R., Ames B. N. Histidine regulatory mutants in Salmonella typhimurium II. Histidine regulatory mutants having altered histidyl-tRNA synthetase. J Mol Biol. 1966 Dec 28;22(2):325–333. doi: 10.1016/0022-2836(66)90135-5. [DOI] [PubMed] [Google Scholar]
  20. SCHLESINGER S., MAGASANIK B. EFFECT OF ALPHA-METHYLHISTIDINE ON THE CONTROL OF HISTIDINE SYNTHESIS. J Mol Biol. 1964 Sep;9:670–682. doi: 10.1016/s0022-2836(64)80174-1. [DOI] [PubMed] [Google Scholar]
  21. Sugimoto E., Pizer L. I. The mechanism of end product inhibition of serine biosynthesis. I. Purification and kinetics of phosphoglycerate dehydrogenase. J Biol Chem. 1968 May 10;243(9):2081–2089. [PubMed] [Google Scholar]
  22. Tosa T., Pizer L. I. Biochemical bases for the antimetabolite action of L-serine hydroxamate. J Bacteriol. 1971 Jun;106(3):972–982. doi: 10.1128/jb.106.3.972-982.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. UMBARGER H. E., UMBARGER M. A., SIU P. M. BIOSYNTHESIS OF SERINE IN ESCHERICHIA COLI AND SALMONELLA TYPHIMURIUM. J Bacteriol. 1963 Jun;85:1431–1439. doi: 10.1128/jb.85.6.1431-1439.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Wanner B. L., Kodaira R., Neidhardt F. C. Physiological regulation of a decontrolled lac operon. J Bacteriol. 1977 Apr;130(1):212–222. doi: 10.1128/jb.130.1.212-222.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Winicov I., Pizer L. I. The mechanism of end product inhibition of serine biosynthesis. IV. Subunit structure of phosphoglycerate dehydrogenase and steady state kinetic studies of phosphoglycerate oxidation. J Biol Chem. 1974 Mar 10;249(5):1348–1355. [PubMed] [Google Scholar]

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