Difference between revisions of "Glycogen phosphorylase"

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Revision as of 10:33, 9 May 2014


Glycogen phosphorylase (GP) is a dimeric enzyme that catalyses the reaction in which the terminal glucose residue from a glycogen chain is phosphorylated and cleaved from the chain, releasing it as Glc1P.

Chemical equation

 Glycogen_{n+1} + Pi \rightleftharpoons Glycogen_{n} + Glc1P

Rate equation

MWC model was used to formualte the rate law. [1]

\frac{V_{max} \times n \times \frac{[Pi]}{K_{r,Pi}} \left( 1 + \frac{[Pi]}{K_{r,Pi}} + \frac{[Glc1P]}{K_{r,Glc1P}}  \right)^{n-1} }{\left( 1 + \frac{[Pi]}{K_{r,Pi}} + \frac{[Glc1P]}{K_{r,Glc1P}} \right)^n + L_u \left( 1 + \frac{[Pi]}{K_{u,Pi}} + \frac{[Glc1P]}{K_{u,Glc1P}}  \right)^n \left(  \frac{1 + \frac{[Glc6P]}{K_{u,Glc6P}}}{1 + \frac{[AMP]}{K_{r,AMP}} + \frac{[Glc6P]}{K_{r,Glc6P}}} \right)^n  }  +  \frac{V_{max} \times n \times \frac{[Pi]}{K_{r,Pi}} \left( 1 + \frac{[Pi]}{K_{r,Pi}} + \frac{[Glc1P]}{K_{r,Glc1P}}  \right)^{n-1} }{\left( 1 + \frac{[Pi]}{K_{r,Pi}} + \frac{[Glc1P]}{K_{r,Glc1P}} \right)^n + L_t \left( 1 + \frac{[Pi]}{K_{t,Pi}} + \frac{[Glc1P]}{K_{t,Glc1P}}  \right)^n \left(  \frac{1 + \frac{[AMP]}{K_{t,AMP}} \frac{[Glc6P]}{K_{t,Glc6P}}}{1 + \frac{[AMP]}{K_{r,AMP}} + \frac{[Glc6P]}{K_{r,Glc6P}}} \right)^n \left( 1 + \frac{[ATP]}{K_{t,ATP}}  \right)^n }




An alternative rate equation without considering the allosteric regulation is given as [2]

 \frac{V_{maxf} \frac{Glycogen_{n+1} \times Pi}{K_{iGlyf} \times K_{Pi}} -\frac{V_{maxf} \times K_{Glyb} \times K_{iGlc1P}}{K_{iGlyf} \times K_{Pi} \times Keq} \times \frac{Glycogen_n \times Glc1P}{K_{Glyb} \times K_{iGlc1P}} }{1 + \frac{Glycogen_{n+1}}{K_{iGlyf}} + \frac{Pi}{K_{iPi}} + \frac{Glycogen_n}{K_{iGlyb}} + \frac{Glc1P}{K_{iGlc1P}} \frac{Glycogen_{n+1} \times Pi}{K_{Glyf} \times K_{iPi}} + \frac{Glycogen_n \times Glc1P}{K_{Glyb} \times K_{iGlc1P}} }

Parameter values

Parameter Value Units Organism Remarks
n 2 Dimensionless Recombinant, human muscle
V_{max} 50 \text{mM min}^{-1}
K_{r,Pi} 2.08 mM
K_{u,Pi} 4.32 mM
K_{t,Pi} 41.53 mM
K_{r, Glc1P} 0.67 mM
K_{u, Glc1P} 82.02 mM
K_{t, Glc1P} 27.92 mM
K_{r, AMP}  3.36 \times 10^{-3} mM
K_{t, AMP} 0.53 mM
K_{t, ATP} 3.9 mM
K_{r, Glc6P} 7.42 mM
K_{u, Glc6P} 0.56 mM
K_{t, Glc6P} 0.27 mM
L_{u} 5.93 Dimensionless
L_{t} 34741 Dimensionless

The parameter for the alternative equation are

Parameter Value Units Organism Remarks
V_{maxf} 50 [1] \text{mM min}^{-1} Rabbit
K_{iGlyf} 15[2] mM
K_{Pi} 4 [2] mM
K_{Glyb} 0.15 [2] mM
K_{iGlc1P} 10.1 [2] mM
K_{iPi} 4.6 [2] mM
K_{iGlyb} 4.4 [2] mM
K_{Glyf} 1.7 [2] mM
Keq 0.42 [2] mM

Parameters with uncertainty

Parameter Value Units Organism Remarks
n 2 Dimensionless Recombinant, human muscle
V_{max} 31.446 \pm 0.917 \text{mM min}^{-1}
K_{r,Pi} 2.08 \pm 0.044 mM
K_{u,Pi} 4.32 \pm 0.177 mM
K_{t,Pi} 41.53 \pm 547.57 mM
K_{r, Glc1P} 0.67 \pm 0.083 mM
K_{u, Glc1P} 82.02 \pm 53.35 mM
K_{t, Glc1P} 27.92 \pm 9.31 mM
K_{r, AMP}  0.00336 \pm 0.00395 mM
K_{t, AMP} 0.53 \pm 0.283 mM
K_{t, ATP} 3.9 \pm 22.627 mM
K_{r, Glc6P} 7.42 \pm 2.73 mM
K_{u, Glc6P} 0.56 \pm 0.12 mM
K_{t, Glc6P} 0.27 \pm 0.0485 mM
L_{u} 5.93 \pm 0.40 Dimensionless
L_{t} 34741 \pm 72931 Dimensionless

The parameter for the alternative equation are

Parameter Value Units Organism Remarks
V_{maxf} 31.446 \pm 0.917 [1] \text{mM min}^{-1} Rabbit
K_{iGlyf} 15[2] mM
K_{Pi} 4 \pm 0.8 [3] mM
K_{Glyb} 0.15 \pm 0.03[3] mM
K_{iGlc1P} 10.1 \pm 2.5 [3] mM
K_{iPi} 4.6 \pm 2.0[3] mM
K_{iGlyb} 4.4 [2] mM
K_{Glyf} 1.7 \pm 0.4[3] mM
Keq 0.36 \pm 0.08 mM Two Keq values of 0.30, 0.42 are reported in [4][2].
Mean and Std. Dev. from these two values are taken.

References

  1. 1.0 1.1 1.2 Palm, D.C. (2013). The regulatory design of glycogen metabolism in mammalian skeletal muscle (Ph.D.). University of Stellenbosch
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 Lambeth M.J. & Kushmerick M.J. (2002). A computational model for glycogenolysis in skeletal muscle. Ann Biomed Eng 30, 808–827
  3. 3.0 3.1 3.2 3.3 3.4 Gold, A. M., R. M. Johnson, and J. K. Tseng (1970), Kinetic mechanism of rabbit muscle glycogen phosphorylase a,J. Biol. Chem. 245:2564 –2572, 1970
  4. Principles of Metabolic Regulation, Book chapter