Pyruvate kinase

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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.

Chemical reaction

 PEP + ADP \rightleftharpoons Pyrvate + ATP

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)

Parameter values

Parameter Value Units Organism Remarks
V_{mf} 195[2]  \text{mM min}^{-1} HeLa cell line
K_{eq}[2] 195172 Recalculated from the ΔGº´ = - 31.4 KJ mol-1.
Km_{PEP}[2] 0.014 mM
Km_{ADP}[2] 0.4 mM
Km_{PYR}[3] 10 mM
Km_{ATP}[3] 0.86 mM
Ka_{F1,6BP}[4] 4\times 10^{-4} mM
Ki_{ATP}[4] 2.5 mM
L[5] 1 Dimensionless
Ka_{SER} 5 mM For allosteric regulation the affinity constant is used. It is the inverted dissociation constant. so  Ka_{SER} = \frac{1}{K_d} where  k_d = 0.2 mM [6]

Alternative parameter values

References

  1. 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. 2.0 2.1 2.2 2.3 Marín-Hernández A, Gallardo-Pérez JC, Rodríguez-Enríquez S et al (2011) Modeling cancer glycolysis. Biochim Biophys Acta 1807:755–767 (doi)
  3. 3.0 3.1 H.U. Bergmeyer. Methods of Enzymatic Analysis. Verlag Chemie, Winheim
  4. 4.0 4.1 Imamura K, Tanaka T (1982). Pyruvate kinase isoenzymes from rat, Methods Enzymol. 90 (1982) 150–165
  5. Arbitrary value
  6. Chaneton, B. et al.(2012) Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature 491, 458–462