Mechanism of the 2,3-diphosphoglycerate-dependent phosphoglycerate mutase from rabbit muscle.
Hubert G. Britton,J B Clarke +1 more
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The very rapid isomersization of the phosphoenzyme that the experiments demonstrate suggests a mechanism that does not involve a formal isomerization, and is closely related mechanistically and perhaps evolutionarily to a 2,3-diphosphoglycerate diphosphatase.Abstract:
1. The properties and kinetics of the 2,3-diphosphoglycerate-dependent phosphoglycerate mutases are discussed. There are at least three possible mechanisms for the reaction: (i) a phosphoenzyme (Ping Pong) mechanism; (ii) an intermolecular transfer of phosphate from 2,3-diphosphoglycerate to the substrates (sequential mechanism); (iii) an intramolecular transfer of phosphate. It is concluded that these mechanisms cannot be distinguished by conventional kinetic measurements. 2. The fluxes for the different mechanisms are calculated and it is shown that it should be possible to distinguish between the mechanisms by appropriate induced-transport tests and by comparing the fluxes of (32)P- and (14)C-labelled substrates at chemical equilibrium. 3. With (14)C-labelled substrates no induced transport was found over a wide concentration range, and with (32)P-labelled substrates co-transport occurred that was independent of concentration over a twofold range. (14)C-labelled substrates exchange at twice the rate of (32)P-labelled substrates at chemical equilibrium. The results were completely in accord with a phosphoenzyme mechanism and indicated a rate constant for the isomerization of the phosphoenzyme of not less than 4x10(6)s(-1). The intramolecular transfer of phosphate (and intermolecular transfer between two or more molecules of substrate) were completely excluded. The intermolecular transfer of phosphate from 2,3-diphosphoglycerate would have been compatible with the results only if the K(m) for 2-phosphoglycerate had been over 7.5-fold smaller than the observed value and if an isomerization of the enzyme-2,3-diphosphoglycerate complex had been the major rate-limiting step in the reaction. 4. The very rapid isomerization of the phosphoenzyme that the experiments demonstrate suggests a mechanism that does not involve a formal isomerization. According to this new scheme the enzyme is closely related mechanistically and perhaps evolutionarily to a 2,3-diphosphoglycerate diphosphatase.read more
Citations
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Book ChapterDOI
The phosphoglycerate mutases.
TL;DR: Available evidence indicates that these mutases are similar in many respects to the much smaller, cofactor-dependent monophosphoglycerate mutase from Schizosaccharomyces pombe, but further information is required to define the relationship more precisely.
Journal ArticleDOI
Post-translational modifications and the Warburg effect
Taro Hitosugi,Jing Chen +1 more
TL;DR: Recent advances revealing how oncogenic and/or tumor suppressive signaling pathways reprogram metabolism through diverse PTMs to provide a metabolic advantage to cancer cells, thereby promoting tumor cell proliferation, tumorigenesis and tumor growth are summarized.
Journal ArticleDOI
Tyr26 phosphorylation of PGAM1 provides a metabolic advantage to tumours by stabilizing the active conformation
Taro Hitosugi,Lu Zhou,Jun Fan,Shannon Elf,Liang Zhang,Jianxin Xie,Yi Wang,Ting-Lei Gu,Maša Alečković,Gary LeRoy,Yibin Kang,Hee-Bum Kang,Jae Ho Seo,Changliang Shan,Peng Jin,Weimin Gong,Sagar Lonial,Martha Arellano,Hanna Jean Khoury,Georgia Z. Chen,Dong M. Shin,Fadlo R. Khuri,Titus J. Boggon,Sumin Kang,Chuan He,Jing Chen +25 more
TL;DR: A novel mechanism in which Y26 phosphorylation enhances PGAM1 activation through release of inhibitory E19 that blocks the active site, stabilising cofactor 2,3-bisphosphoglycerate binding and H11 phosphorylated is reported.
Book ChapterDOI
[66] Phosphoglycerate mutase from yeast, chicken breast muscle, and kidney (2,3-PGA-dependent)
S. Grisolia,J. Carreras +1 more
Journal ArticleDOI
Rates of phosphorylation and dephosphorylation of phosphoglycerate mutase and bisphosphoglycerate synthase.
TL;DR: It is concluded that the phosphorylated enzymes have kinetic properties consistent with their participation as intermediates in the reactions catalyzed by these enzymes.
References
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Journal ArticleDOI
The specific precipitation of orthophosphate and some biochemical applications.
Yukio Sugino,Yukiko Miyoshi +1 more
Journal ArticleDOI
Separation of adenosine phosphates by paper chromatography and the equilibrium constant of the myokinase system
L. V. Eggleston,R. Hems +1 more
Journal ArticleDOI
The occurrence of a group transfer involving enzyme (phosphoglucomutase) and substrate.
Journal ArticleDOI
Evidence for a phosphohistidine protein intermediate in the phosphoglycerate mutase reaction.
TL;DR: The pH and time dependence of the release of the 32P from the phosphorylated enzyme at 46 ° agree with the lability of 3-phosphohistidine, and electrophoresis on polyacrylamide gels containing sodium dodecyl sulfate indicates that the combining weight of the32P-contaimng species is about half of the reported molecular weight.
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