Studies on the Control of Hexosamine Biosynthesis by Glucosamine Synthetase

Overview

Journal Biochem J

Specialty Biochemistry

Date 1971 Feb 1

PMID 5114979

Citations 12

Authors

P J Winterburn

C F Phelps

Affiliations

Soon will be listed here.

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.

Citing Articles

Azide- and Alkyne-Bearing Metabolic Chemical Reporters of Glycosylation Show Structure-Dependent Feedback Inhibition of the Hexosamine Biosynthetic Pathway.

Walter L, Batt A, Darabedian N, Zaro B, Pratt M Chembiochem. 2018; 19(18):1918-1921.

PMID: 29979493 PMC: 6261355. DOI: 10.1002/cbic.201800280.

Genetic and structural validation of Aspergillus fumigatus UDP-N-acetylglucosamine pyrophosphorylase as an antifungal target.

Fang W, Du T, Raimi O, Hurtado-Guerrero R, Urbaniak M, Ibrahim A Mol Microbiol. 2013; 89(3):479-93.

PMID: 23750903 PMC: 3888555. DOI: 10.1111/mmi.12290.

Regulation of the hexosamine biosynthetic pathway in the water mold Blastocladiella emersonii: Sensitivity to endproduct inhibition is dependent upon the life cycle phase.

Selitrennikoff C, Dalley N, Sonneborn D Proc Natl Acad Sci U S A. 1980; 77(10):5998-6002.

PMID: 16592895 PMC: 350200. DOI: 10.1073/pnas.77.10.5998.

UDP-sugar metabolism in Swarm rat chondrosarcoma chondrocytes.

Sweeney C, Mackintosh D, Mason R Biochem J. 1993; 290 ( Pt 2):563-70.

PMID: 8452547 PMC: 1132311. DOI: 10.1042/bj2900563.

Coordinated regulation of amino sugar-synthesizing and -degrading enzymes in Escherichia coli K-12.

Plumbridge J, Cochet O, Souza J, Altamirano M, Calcagno M, Badet B J Bacteriol. 1993; 175(16):4951-6.

PMID: 8349539 PMC: 204958. DOI: 10.1128/jb.175.16.4951-4956.1993.

References

Collins D, Jirku H, Layne D . Steroid N-acetylglucosaminyl transferase. Localization and some properties of the enzyme in rabbit tissues. J Biol Chem. 1968; 243(11):2928-33. View

Till U, Blume E, Gunther J, Reich J, Zahn D, Klinger R . Determination of specific radioactivities of mononucleotides and glycolytic intermediates from mouse liver after labelling in vivo with [32P]orthophosphate. Eur J Biochem. 1968; 6(3):373-83. DOI: 10.1111/j.1432-1033.1968.tb00458.x. View

Spiro R . Studies on the biosynthesis of glucosamine in the intact rat. J Biol Chem. 1959; 234(4):742-8. View

Winterburn P, Phelps C . Purification and some kinetic properties of rat liver glucosamine synthetase. Biochem J. 1971; 121(4):701-9. PMC: 1176648. DOI: 10.1042/bj1210701. View

KORNFELD R . Studies on L-glutamine D-fructose 6-phosphate amidotransferase. I. Feedback inhibition by uridine diphosphate-N-acetylglucosamine. J Biol Chem. 1967; 242(13):3135-41. View

Start C, Newsholme E . The effects of starvation and alloxan-diabetes on the contents of citrate and other metabolic intermediates in rat liver. Biochem J. 1968; 107(3):411-5. PMC: 1198678. DOI: 10.1042/bj1070411. View

Brosnan J, KREBS H, Williamson D . Effects of ischaemia on metabolite concentrations in rat liver. Biochem J. 1970; 117(1):91-6. PMC: 1178834. DOI: 10.1042/bj1170091. View

Bates C, Handschumacher R . 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. View

VON EULER L, RUBIN R, Handschumacher R . Fatty livers induced by orotic acid. II. Changes in nucleotide metabolism. J Biol Chem. 1963; 238:2464-9. View

10.

Spiro R . Role of insulin in two pathways of glucose metabolism: in vivo glucosamine and glycogen synthesis. Ann N Y Acad Sci. 1959; 82:366-73. DOI: 10.1111/j.1749-6632.1959.tb44917.x. View

11.

Engel P, 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; 115(4):621-31. PMC: 1185186. DOI: 10.1042/bj1150621. View

12.

Kornfeld S, KORNFELD R, Neufeld E, OBrien P . THE FEEDBACK CONTROL OF SUGAR NUCLEOTIDE BIOSYNTHESIS IN LIVER. Proc Natl Acad Sci U S A. 1964; 52:371-9. PMC: 300286. DOI: 10.1073/pnas.52.2.371. View

13.

Winterburn P, Phelps C . Relevance of feedback inhibition applied to the biosynthesis of hexosamines. Nature. 1970; 228(5278):1311-3. DOI: 10.1038/2281311a0. View

14.

Atkinson D . The energy charge of the adenylate pool as a regulatory parameter. Interaction with feedback modifiers. Biochemistry. 1968; 7(11):4030-4. DOI: 10.1021/bi00851a033. View

15.

Hardingham T, Phelps C . The tissue content and turnover rates of intermediates in the biosynthesis of glycosaminoglycans in young rat skin. Biochem J. 1968; 108(1):9-16. PMC: 1198763. DOI: 10.1042/bj1080009. View

16.

Gevers W, KREBS H . The effects of adenine nucleotides on carbohydrate metabolism in pigeon-liver homogenates. Biochem J. 1966; 98(3):720-35. PMC: 1264913. DOI: 10.1042/bj0980720. View

17.

Reich J, Till U, Gunther 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; 6(3):384-94. DOI: 10.1111/j.1432-1033.1968.tb00459.x. View

18.

Hornbrook K, Burch H, LOWRY O . CHANGES IN SUBSTRATE LEVELS IN LIVER DURING GLYCOGEN SYNTHESIS INDUCED BY LACTATE AND HYDROCORTISONE. Biochem Biophys Res Commun. 1965; 18:206-11. DOI: 10.1016/0006-291x(65)90741-2. View

19.

Izumi K . INTRACELLULAR DISTRIBUTION OF ENZYMES INVOLVED IN GLUCOSAMINE METABOLISM IN RAT LIVER. J Biochem. 1965; 57:539-46. DOI: 10.1093/oxfordjournals.jbchem.a128112. View

20.

Mazlen R, Muellenberg C, OBrien P . The control of L-glutamine-D-fructose-6-phosphate amidotransferase in bovine retina. Biochim Biophys Acta. 1969; 171(2):352-4. DOI: 10.1016/0005-2744(69)90168-5. View