Difference between revisions of "Glyceraldehyde-3-phosphate dehydrogenase"

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| Lehninger, (2008)<ref name="lehninger2008">David L. Nelson, Michael M. Cox (2008), Lehninger Principles of Biochemistry (5th edn), W. H. Freeman and Company</ref> p 553:<br/>
 
| Lehninger, (2008)<ref name="lehninger2008">David L. Nelson, Michael M. Cox (2008), Lehninger Principles of Biochemistry (5th edn), W. H. Freeman and Company</ref> p 553:<br/>
 
<math>\Delta G' = 6.3\ kJ.mol^{-1}</math>, <math>Keq = exp(-\frac{\Delta G'}{RT}) = exp(\frac{-6300}{8.31*298.15}) \approx 0.078</math>
 
<math>\Delta G' = 6.3\ kJ.mol^{-1}</math>, <math>Keq = exp(-\frac{\Delta G'}{RT}) = exp(\frac{-6300}{8.31*298.15}) \approx 0.078</math>
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| 0.067
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| pH=7, T=25°C
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| Voet et al.<ref name="voet">Voet, D., Voet., J.G. and Pratt, C. W. (1999) Fundamentals of biochemistry, Wiley</ref> from Newshole et al. (1973) <ref name="newshole73">Newshole, E.A. and Stuart, C. (1973) Regulation in Metabolism, Wiley</ref>p 97:<br/>
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<math>\Delta G' = 6.7\ kJ.mol^{-1}</math>, <math>Keq = exp(-\frac{\Delta G'}{RT}) = exp(\frac{-6300}{8.31*298.15}) \approx 0.067</math>
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| 0.08
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| pH=7, T=298.15
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| Corrected for pH from Cori et al. 1950 (NIST database<ref name="nist">Goldberg R.N., Tewari Y.B. and Bhat T.N. (2004) Bioinformatics 20(16):2874-2877 [[http://www.ncbi.nlm.nih.gov/pubmed?term=15145806 pmid: 15145806]]</ref> [[http://xpdb.nist.gov/enzyme_thermodynamics/enzyme_data1.pl?T1=50COR/VEL_252 50COR/VEL_252]]) pH=7.09
 
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==References==
 
==References==
 
<references/>
 
<references/>

Revision as of 10:37, 1 July 2014

The Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) enzyme serves two functions in glycolytic pathway. First the enzyme transfers a hydrogen (H-) from glyceraldehyde phosphate (Gly3P) to the oxidizing agent Nicotinamide Adenine Dinucleotide (NAD+) to form NADH. Next it adds a phosphate (P) from the cytosol to the oxidized Gly3P to form 1, 3-bisphosphoglycerate.

Chemical equation

NAD + Gly3P + Pi \rightleftharpoons 1,3BPG + NADH

Rate equation

Ordererd Ter-Bi reversible Michaelis-Menten equation for non-interacting substrates. [1]

v = \frac{ V_{mf}\frac{[NAD][Gly3P][Pi]}{K_{NAD}K_{Gly3P}K_{Pi}} - V_{mr} \frac{[1,3BPG][NADH]}{K_{1,3BPG}K_{NADH}} }{1 + \frac{[NAD]}{K_{NAD}} + \frac{[NAD][Gly3P]}{K_{NAD}K_{Gly3P}} + \frac{[NAD][Gly3P][Pi]}{K_{NAD}K_{Gly3P}K_{Pi}} + \frac{[1,3BPG][NADH]}{K_{1,3BPG}K_{NADH}} +\frac{[NADH]}{K_{NADH}} }

Modified rate law for taking Thermodynamic constant into consideration

v = \frac{ V_{mf}\frac{[NAD][Gly3P][Pi]}{K_{NAD}K_{Gly3P}K_{Pi}} \left( 1 - \frac{[1,3BPG][NADH]}{K_{eq}[NAD][Gly3P][Pi]} \right)}{1 + \frac{[NAD]}{K_{NAD}} + \frac{[NAD][Gly3P]}{K_{NAD}K_{Gly3P}} + \frac{[NAD][Gly3P][Pi]}{K_{NAD}K_{Gly3P}K_{Pi}} + \frac{[1,3BPG][NADH]}{K_{1,3BPG}K_{NADH}} +\frac{[NADH]}{K_{NADH}} }

Parameters

Parameter Value Units Organism Remarks
V_{mf} 0.58 [2] mM \times min^{-1} HeLa cell line
V_{mr} 0.72[2] mM \times min^{-1}
Km_{Gly3P} 0.19[1] mM
Km_{1,3BPG} 0.022[1] mM
Km_{NAD+} 0.09[1] mM
Km_{NADH} 0.01[1] mM
Km_{Pi} 29[1] mM

Parameters with uncertainty

  • Four values of Km_{NADH} have been collected from Lambeir et. al. (1991)[3] for different organisms. Km_{NADH} = 0.007 for Trypanosoma brucei, Km_{NADH} = 0.01 for Homo sapiens, Km_{NADH} = 0.012 for Geobacillus stearothermophilus and Km_{NADH} = 0.012 for Oryctolagus cuniculus. Calculating mean and std. dev. from these 4 values gives Km_{NADH} = 0.01025 \pm 0.002046
  • Three values collected under different conditions from human cell is reported for Km_{NAD+} in Ryzlak (1998) et. al. [4]. Those values are 0.01, 0.02, 0.027. The mean and Std. Dev. from these three values are Km_{NAD+} = 0.019 \pm 0.007
  • Three values for Km_{1,3BPG} have also been reported under different conditions from human cell in Ryzlak (1998) et. al. [4]. Those values are 0.01, 0.012, 0.018. The mean and Std. Dev. from these three values are Km_{1,3BPG} = 0.013 \pm 0.0035
  • Three values for Km_{Gly3P} have also been reported under different conditions from human cell in Ryzlak (1998) et. al. [4]. Those values are 0.032, 0.035, 0.042. The mean and Std. Dev. from these three values are Km_{Gly3P} = 0.036 \pm 0.0042
Parameter Value Units Organism Remarks
V_{mf} 2 \pm 0.74 (5) [2] mM \times min^{-1} HeLa cell line
V_{mr} 2.5 \pm 0.8 (5)[2] mM \times min^{-1}
Km_{Gly3P} 0.036 \pm 0.0042 mM Human brain
Km_{1,3BPG} 0.013 \pm 0.0035 mM Human brain
Km_{NAD+} 0.019 \pm 0.007 mM Human brain
Km_{NADH} 0.01025 \pm 0.002046 mM Multiple organism
Km_{Pi} 4 \pm 0.2[5] mM Normal tissue in human

Equilibrium constant

Equilibrium constant Conditions Source
0.078 pH=7, T=25°C Lehninger, (2008)[6] p 553:

\Delta G' = 6.3\ kJ.mol^{-1}, Keq = exp(-\frac{\Delta G'}{RT}) = exp(\frac{-6300}{8.31*298.15}) \approx 0.078

0.067 pH=7, T=25°C Voet et al.[7] from Newshole et al. (1973) [8]p 97:

\Delta G' = 6.7\ kJ.mol^{-1}, Keq = exp(-\frac{\Delta G'}{RT}) = exp(\frac{-6300}{8.31*298.15}) \approx 0.067

0.08 pH=7, T=298.15 Corrected for pH from Cori et al. 1950 (NIST database[9] [50COR/VEL_252]) pH=7.09

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S et al (2011) Modeling cancer glycolysis. Biochim Biophys Acta 1807:755–767 (doi)
  2. ↑ 2.0 2.1 2.2 2.3 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)
  3. ↑ Lambeir, A.M.; Loiseau, A.M.; Kuntz, D.A.; Vellieux, F.M.; Michels, P.A.M.; Opperdoes, F.R. (1991), The cytosolic and glycosomal glyceraldehyde-3-phosphate dehydrogenase from Trypanosoma brucei. Kinetic properties and comparison with homologous enzymes, Eur. J. Biochem. 198, 429-435
  4. ↑ 4.0 4.1 4.2 Ryzlak, M.T.; Pietruszko, R. (1998), Heterogeneity of glyceraldehyde-3-phosphate dehydrogenase from human brain, Biochim. Biophys. Acta 954, 309-324
  5. ↑ Patra, S.; Ghosh, S.; Bera, S.; Roy, A.; Ray, S.; Ray, M. (2009), Molecular characterization of tumor associated glyceraldehyde-3-phosphate dehydrogenase, Biochemistry (Moscow) 74, 717-727
  6. ↑ David L. Nelson, Michael M. Cox (2008), Lehninger Principles of Biochemistry (5th edn), W. H. Freeman and Company
  7. ↑ Voet, D., Voet., J.G. and Pratt, C. W. (1999) Fundamentals of biochemistry, Wiley
  8. ↑ Newshole, E.A. and Stuart, C. (1973) Regulation in Metabolism, Wiley
  9. ↑ Goldberg R.N., Tewari Y.B. and Bhat T.N. (2004) Bioinformatics 20(16):2874-2877 [pmid: 15145806]
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