Difference between revisions of "Pyruvate kinase"
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*Two values of <math>Km_{ATP}</math> have been reported in the literature. 0.35 for Sparus aurata liver <ref name="Gomez_Milan_2007"></ref> and 0.86 <ref name="Bergmeyer_1983"></ref>. The uncertainty is then <math>0.60 \pm 0.36</math>. | *Two values of <math>Km_{ATP}</math> have been reported in the literature. 0.35 for Sparus aurata liver <ref name="Gomez_Milan_2007"></ref> and 0.86 <ref name="Bergmeyer_1983"></ref>. The uncertainty is then <math>0.60 \pm 0.36</math>. | ||
− | *Two values of Serine activation for Pyruvate Kinase constant have been reported; 2<ref name="Merrins_2013">M.J. Merrins, A.R. Van Dyke, A.K. Mapp, M.A. Rizzo, L.S. Satin (2013), ''Direct measurements of oscillatory glycolysis in pancreatic islet beta-cells using novel fluorescence resonance energy transfer (FRET) biosensors for pyruvate kinase M2 activity''. J. Biol. Chem. 288, 33312–33322</ref> and 5 <ref name="Chaneton_2012></ref>. Taking mean and Std. Dev. for this two value gives <math>3.5 \pm 2.12</math>. | + | *Two values of Serine activation for Pyruvate Kinase constant have been reported; 2<ref name="Merrins_2013">M.J. Merrins, A.R. Van Dyke, A.K. Mapp, M.A. Rizzo, L.S. Satin (2013), ''Direct measurements of oscillatory glycolysis in pancreatic islet beta-cells using novel fluorescence resonance energy transfer (FRET) biosensors for pyruvate kinase M2 activity''. J. Biol. Chem. 288, 33312–33322</ref> and 5 <ref name="Chaneton_2012"></ref>. Taking mean and Std. Dev. for this two value gives <math>3.5 \pm 2.12</math>. |
* The <math>K_{eq}</math> values found in the literature are ΔGº´ = -23.0 | -31.4 | -24.98 | -26.815 kJ/mol, =>Keq = 7509 | 195452 | 16190 | 32995 | * The <math>K_{eq}</math> values found in the literature are ΔGº´ = -23.0 | -31.4 | -24.98 | -26.815 kJ/mol, =>Keq = 7509 | 195452 | 16190 | 32995 |
Revision as of 14:38, 15 May 2014
Pyruvate kinase is a transferase enzyme that catalyzes the transfer of a phosphate group from phosphoenolpyruvate (PEP) to ADP, yielding one molecule of pyruvate and one molecule of ATP.
Contents
Chemical reaction
![PEP + ADP \rightleftharpoons Pyrvate + ATP](/wiki/images/math/6/a/e/6aefc45d5babff149006084e4e37f222.png)
Rate equation
The rate equation is represented by the allosteric regualation model of Monod, Wyman and Changeux (MWS). Fru1,6BP and Serine are activators and ATP is inhibiting. Simple Micahelis-Menten kinetics (Briggs Haldane) is used for ADP and reverse reaction [1]
![v=V_m \left( \left(\frac{\frac{[ADP]}{K_{ADP}}}{1+\frac{[ADP]}{K_{ADP}}}\right) \left( \frac{\frac{[PEP]}{Km_{PEP}}\left( 1+\frac{[PEP]}{Km_{PEP}} \right)^3 }{ \frac{L \left( 1 + \frac{[ATP]}{Ki_{ATP}} \right)^4 }{ \left( 1 + \frac{[SER]}{Ka_{SER}} \right)^4 \left( 1 + \frac{F1,6BP}{Ka_{F1,6BP}} \right)^4 } + \left( 1 + \frac{[PEP]}{Km_{PEP}} \right)^4} \right) - \left( \frac{\frac{[ATP][PYR]}{K_{ATP} \times K_{PYR} \times K_{eq}}}{1 +\frac{[ATP]}{K_{ATP}} + \frac{[PYR]}{K_{PYR}} + \frac{[ATP][PYR]}{K_{ATP} \times K_{PYR} }} \right) \right)](/wiki/images/math/6/0/8/608585715d214881c663ba97b3810b40.png)
Parameter values
- The dissociation constant is commonly used to describe the affinity between a ligand (L) (such as a drug) and a protein (P) i.e. how tightly a ligand binds to a particular protein. In the specific case of antibodies (Ab) binding to antigen (Ag), usually the affinity constant is used. It is the inverted dissociation constant.
Parameter | Value | Units | Organism | Remarks |
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1.9[2] | ![]() |
HeLa cell line | |
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195172 | Recalculated from the ΔGº´ = - 31.4 KJ mol-1. | ||
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0.014 | mM | ||
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0.4 | mM | ||
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10 | mM | ||
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0.86 | mM | ||
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mM | ||
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2.5 | mM | ||
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1 | Dimensionless | ||
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5 | mM | For allosteric regulation the affinity constant is used. It is the inverted dissociation constant. so ![]() ![]() |
Parameters with uncertainty
- Three values of
have been reported as 0.14, 0.12, 0.33 in Boyer et. al. (1969) [7]. The Mean and Std. Dev. is Failed to parse (Cannot store math image on filesystem.): 0.19 \pm 0.09 .
- Four isoforms of PYK exists. Among those four, three isoforms (R, L and M2) exhibits cooperative kinetics activated by Fru1,6BP (Ka = 0.00006 - 0.0004). For calculating the mean and standard deviation we consider max = 0.0004 and min = 0.00006. The range rule tells that the mean of a sample is the average of the maximum and the minimum value and standard deviation is approximately equal to one fourth of the range of the data ie. s = (Maximum – Minimum)/4. So the mean is (0.0004 + 0.00006)/2= 0.00023 and std. dev. = 0.000085[8].
- Four values for
found in the literature are 0.025,0.055 [9] for Sparus aurata liver, 0.48 for Selenomonas ruminantium [10] and 10 [3]. The mean and std. dev. from these 4 values are 2.64 and 4.9.
- Two values of
have been reported in the literature. 0.35 for Sparus aurata liver [9] and 0.86 [3]. The uncertainty is then
.
- Two values of Serine activation for Pyruvate Kinase constant have been reported; 2[11] and 5 [6]. Taking mean and Std. Dev. for this two value gives
.
- The
values found in the literature are ΔGº´ = -23.0 | -31.4 | -24.98 | -26.815 kJ/mol, =>Keq = 7509 | 195452 | 16190 | 32995
Parameter | Value | Units | Organism | Remarks |
---|---|---|---|---|
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HeLa cell line | |
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Failed to parse (Cannot store math image on filesystem.): 63036 \pm 76997 (n=4) | Recalculated from the ΔGº´ = - 31.4 KJ mol-1. | ||
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Failed to parse (Cannot store math image on filesystem.): 0.17 \pm 0.01 [13] | mM | ||
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mM | ||
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mM | ||
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mM | ||
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mM | ||
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Failed to parse (Cannot store math image on filesystem.): 0.19 \pm 0.09 [7] | mM | ||
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Dimensionless | ||
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mM |
References
- ↑ Monod J, Wyman J, Changeux J-P (1965). On the Nature of Allosteric Transitions: A Plausible Model . Journal of Molecular Biology 12:88–118 (doi)
- ↑ 2.0 2.1 2.2 2.3 2.4 Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S et al (2011) Modeling cancer glycolysis. Biochim Biophys Acta 1807:755–767 (doi)
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 H.U. Bergmeyer. Methods of Enzymatic Analysis. Verlag Chemie, Winheim
- ↑ 4.0 4.1 4.2 Imamura K, Tanaka T (1982). Pyruvate kinase isoenzymes from rat, Methods Enzymol. 90 (1982) 150–165
- ↑ Arbitrary value
- ↑ 6.0 6.1 Chaneton, B. et al.(2012) Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 491, 458–462
- ↑ 7.0 7.1 P.D. Boyer (1969, The inhibition of pyruvate kinase by ATP: A Mg++ buffer system for use in enzyme studies, Biochemical and Biophysical Research Communications, Volume 34, Issue 5, 10 March 1969, Pages 702–706
- ↑ A. Marín-Hernández, J.C. Gallardo-Pérez, S.J. Ralph, S. Rodríguez-Enríquez, R. Moreno-Sánchez (2009), HIF-1alpha modulates energy metabolism in cancer cells by inducing over-expression of specific glycolytic isoforms, Mini Rev. Med. Chem., 9, pp. 1084–1101
- ↑ 9.0 9.1 Gomez-Milan E., Cardenete G., Sanchez-Muros M.J. (2007), Annual variations in the specific activity of fructose 1,6-bisphosphatase, alanine aminotransferase and pyruvate kinase in the Sparus aurata liver, Comp. Biochem. Physiol. B 147, 49-55
- ↑ Asanuma N., Hino T. (2001), Molecular characterization, enzyme properties and transcriptional regulation of phosphoenolpyruvate carboxykinase and pyruvate kinase in a ruminal bacterium, Selenomonas ruminantium, Microbiology 147, 681-690 (2001)
- ↑ M.J. Merrins, A.R. Van Dyke, A.K. Mapp, M.A. Rizzo, L.S. Satin (2013), Direct measurements of oscillatory glycolysis in pancreatic islet beta-cells using novel fluorescence resonance energy transfer (FRET) biosensors for pyruvate kinase M2 activity. J. Biol. Chem. 288, 33312–33322
- ↑ Marín-Hernández A , Rodríguez-Enríquez S, Vital-González P A, et al. (2006). Determining and understanding the control of glycolysis in fast-growth tumor cells. Flux control by an over-expressed but strongly product-inhibited hexokinase. FEBS J., 273 , pp. 1975–1988(doi)
- ↑ 13.0 13.1 Dombrauckas, J. D., Santarsiero, B. D. & Mesecar, A. D. (2005) Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis. Biochemistry 44, 9417–9429
- ↑ del Valle,P.,de Arriaga, D., Busto, F. and Soler, J. (1986) A study of the allosteric kinetics of Phycomyces pyruvate kinase as judged by the effect of e-alanine and fructose 1,6-bisphosphate. Biochim. Biophys. Acta 874, 193-204