Skip to main content
NCBI home page
Biochemical Journal logoLink to Biochemical Journal
. 1971 Feb;121(4):711–720. doi: 10.1042/bj1210711

Studies on the control of hexosamine biosynthesis by glucosamine synthetase

P J Winterburn 1,*, C F Phelps 1
PMCID: PMC1176649  PMID: 5114979

Abstract

1. The nature of the feedback inhibition of hexosamine biosynthesis on rat liver glucosamine synthetase (l-glutamine–d-fructose 6-phosphate aminotransferase, EC 2.6.1.16) by UDP-N-acetylglucosamine was investigated in detail. 2. Further modifiers of physiological importance are described. Glucose 6-phosphate and AMP potentiated the UDP-N-acetylglucosamine inhibition, and UTP behaved as an activator. These three compounds only exerted their action when the feedback inhibitor was bound to the enzyme. 3. ATP also inhibited the enzyme. 4. The actions of these various effectors are discussed in kinetic terms. 5. An interpretation of these findings with reference to the regulation of hexosamine biosynthesis is presented.

Full text

PDF
711

Selected References

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

  1. Atkinson D. E. The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry. 1968 Nov;7(11):4030–4034. doi: 10.1021/bi00851a033. [DOI] [PubMed] [Google Scholar]
  2. Bates C. J., Adams W. R., Handschumacher R. E. Control of the formation of uridine diphospho-N-acetyl-hexosamine and glycoprotein synthesis in rat liver. J Biol Chem. 1966 Apr 25;241(8):1705–1712. [PubMed] [Google Scholar]
  3. Bates C. J., Handschumacher R. E. Inactivation and resynthesis of glucosamine-6-phosphate synthetase after treatment with glutamine analogs. Adv Enzyme Regul. 1969;7:183–204. doi: 10.1016/0065-2571(69)90018-1. [DOI] [PubMed] [Google Scholar]
  4. Brosnan J. T., Krebs H. A., Williamson D. H. Effects of ischaemia on metabolite concentrations in rat liver. Biochem J. 1970 Mar;117(1):91–96. doi: 10.1042/bj1170091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. CLELAND W. W. The kinetics of enzyme-catalyzed reactions with two or more substrates or products. II. Inhibition: nomenclature and theory. Biochim Biophys Acta. 1963 Feb 12;67:173–187. doi: 10.1016/0006-3002(63)91815-8. [DOI] [PubMed] [Google Scholar]
  6. Collins D. C., Jirku H., Layne D. S. Steroid N-acetylglucosaminyl transferase. Localization and some properties of the enzyme in rabbit tissues. J Biol Chem. 1968 Jun 10;243(11):2928–2933. [PubMed] [Google Scholar]
  7. Endo M., Yosizawa Z. Hormonal effect on sugar-nucleotides in rabbit uteri. Arch Biochem Biophys. 1968 Sep 20;127(1):585–589. doi: 10.1016/0003-9861(68)90266-x. [DOI] [PubMed] [Google Scholar]
  8. Engel P. C., Dalziel K. Kinetic studies of glutamate dehydrogenase with glutamate and norvaline as substrates. Coenzyme activation and negative homotropic interactions in allosteric enzymes. Biochem J. 1969 Dec;115(4):621–631. doi: 10.1042/bj1150621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gevers W., Krebs H. A. The effects of adenine nucleotides on carbohydrate metabolism in pigeon-liver homogenates. Biochem J. 1966 Mar;98(3):720–735. doi: 10.1042/bj0980720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. HORNBROOK K. R., BURCH H. B., LOWRY O. H. CHANGES IN SUBSTRATE LEVELS IN LIVER DURING GLYCOGEN SYNTHESIS INDUCED BY LACTATE AND HYDROCORTISONE. Biochem Biophys Res Commun. 1965 Jan 18;18:206–211. doi: 10.1016/0006-291x(65)90741-2. [DOI] [PubMed] [Google Scholar]
  11. Hardingham T. E., Phelps C. F. The tissue content and turnover rates of intermediates in the biosynthesis of glycosaminoglycans in young rat skin. Biochem J. 1968 Jun;108(1):9–16. doi: 10.1042/bj1080009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. IZUMI K. INTRACELLULAR DISTRIBUTION OF ENZYMES INVOLVED IN GLUCOSAMINE METABOLISM IN RAT LIVER. J Biochem. 1965 Apr;57:539–546. doi: 10.1093/oxfordjournals.jbchem.a128112. [DOI] [PubMed] [Google Scholar]
  13. KORNFELD S., KORNFELD R., NEUFELD E. F., O'BRIEN P. J. THE FEEDBACK CONTROL OF SUGAR NUCLEOTIDE BIOSYNTHESIS IN LIVER. Proc Natl Acad Sci U S A. 1964 Aug;52:371–379. doi: 10.1073/pnas.52.2.371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kirtley M. E., Koshland D. E., Jr Models for cooperative effects in proteins containing subunits. Effects of two interacting ligands. J Biol Chem. 1967 Sep 25;242(18):4192–4205. [PubMed] [Google Scholar]
  15. Kornfeld R. Studies on L-glutamine D-fructose 6-phosphate amidotransferase. I. Feedback inhibition by uridine diphosphate-N-acetylglucosamine. J Biol Chem. 1967 Jul 10;242(13):3135–3141. [PubMed] [Google Scholar]
  16. Mazlen R. G., Muellenberg C. G., O'Brien P. J. The control of L-glutamine-D-fructose-6-phosphate amidotransferase in bovine retina. Biochim Biophys Acta. 1969 Feb 11;171(2):352–354. doi: 10.1016/0005-2744(69)90168-5. [DOI] [PubMed] [Google Scholar]
  17. Reich J. G., Till U., Günther J., Zahn D., Tschisgale M., Frunder H. Enzymic flux rates in vivo through the Embden-Meyerhof pathway and the nucleotides of the mouse liver. Eur J Biochem. 1968 Nov;6(3):384–394. doi: 10.1111/j.1432-1033.1968.tb00459.x. [DOI] [PubMed] [Google Scholar]
  18. SPIRO R. G. Role of insulin in two pathways of glucose metabolism: in vivo glucosamine and glycogen synthesis. Ann N Y Acad Sci. 1959 Sep 25;82:366–373. doi: 10.1111/j.1749-6632.1959.tb44917.x. [DOI] [PubMed] [Google Scholar]
  19. SPIRO R. G. Studies on the biosynthesis of glucosamine in the intact rat. J Biol Chem. 1959 Apr;234(4):742–748. [PubMed] [Google Scholar]
  20. Start C., Newsholme E. A. The effects of starvation and alloxan-diabetes on the contents of citrate and other metabolic intermediates in rat liver. Biochem J. 1968 Apr;107(3):411–415. doi: 10.1042/bj1070411. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Till U., Blume E., Günther J., Reich J. G., Zahn D., Klinger R., Jaroszewicz K., Frunder H. Determination of specific radioactivities of mononucleotides and glycolytic intermediates from mouse liver after labelling in vivo with [32P]orthophosphate. Eur J Biochem. 1968 Nov;6(3):373–383. doi: 10.1111/j.1432-1033.1968.tb00458.x. [DOI] [PubMed] [Google Scholar]
  22. VON EULER L. H., RUBIN R. J., HANDSCHUMACHER R. E. Fatty livers induced by orotic acid. II. Changes in nucleotide metabolism. J Biol Chem. 1963 Jul;238:2464–2469. [PubMed] [Google Scholar]
  23. Winterburn P. J., Phelps C. F. Purification and some kinetic properties of rat liver glucosamine synthetase. Biochem J. 1971 Feb;121(4):701–709. doi: 10.1042/bj1210701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Winterburn P. J., Phelps C. F. Relevance of feedback inhibition applied to the biosynthesis of hexosamines. Nature. 1970 Dec 26;228(5278):1311–1313. doi: 10.1038/2281311a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES