Difference between revisions of "Nucleosid diphosphate kinase"

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(Parameters with uncertainty)
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* Two values of <math>V_{max}</math> is also reported in Fukuchi (1994) et. al. <ref name="Fukuchi_1994"></ref>; 126 (4.20 <math>\text{mmol min}^{-1}\text{ mg}^{-1}</math> multiplied with 30 mg)  and 138 (4.60 <math>\text{mmol min}^{-1}\text{ mg}^{-1}</math> multiplied with 30 mg) <math>\text{mmol min}^{-1}</math>. Taking average gives <math>132 \pm 8.48</math>.
 
* Two values of <math>V_{max}</math> is also reported in Fukuchi (1994) et. al. <ref name="Fukuchi_1994"></ref>; 126 (4.20 <math>\text{mmol min}^{-1}\text{ mg}^{-1}</math> multiplied with 30 mg)  and 138 (4.60 <math>\text{mmol min}^{-1}\text{ mg}^{-1}</math> multiplied with 30 mg) <math>\text{mmol min}^{-1}</math>. Taking average gives <math>132 \pm 8.48</math>.
  
*Standard free energy <math>\Delta G^{o}{'}</math> is reported to be zero kJ/mol. Therefore the value of Keq is assumed to be constant.
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*Standard free energy <math>\Delta G^{o}{'}</math> is reported to be zero kJ/mol. Therefore the value of Keq can be assumed to be constant. As there was no reported other value std. dev. from other Keq values are considered which is <math>\approx 30%</math>. So the Keq value would be <math>1 \pm 0.3</math>
  
 
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|<math>K_{eq}</math>
 
|<math>K_{eq}</math>
|<math>1</math>
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|<math>1 \pm .3</math>
 
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Revision as of 15:49, 28 May 2014

Nucleoside-diphosphate kinases are enzymes that catalyze the exchange of phosphate groups between different nucleotides. The overall effect of NDKs is to transfer a phosphate group from a nucleoside triphosphate to a nucleoside diphosphate. Starting with ATP and UDP, the activity of NDK produces ADP and UTP.

Chemical equation

ATP + UDP \leftrightarrow ADP + UTP

Rate equation

Random order Bi-Bi rate law is used from [1]

\frac{ \frac{V_{max}}{K_m^{ATP}K_m^{UDP}}\left( [ATP][UDP] - \frac{[ADP][UTP]}{K_{eq}}  \right)  }  { \left( 1 + \frac{[ATP]}{K_{m}^{ATP}}  \right)\left( 1 + \frac{[UDP]}{K_{m}^{UDP}}  \right) + \left( 1 + \frac{[ADP]}{K_{m}^{ADP}}  \right)\left( 1 + \frac{[UTP]}{K_{m}^{UTP}}  \right) -1 }


Parameter values

  • A mean body weight is defined as 75Kg in Konig et. al [1]. The V_{max} is calculated by multiplying the reported value with body weight.
Parameter Value Units Organism Remarks
V_{max} 131.25 [2] min^{-1} Human Liver
K_{m}^{ATP}  1.33 [3] mM Rat liver
K_{m}^{ADP} 0.042[3] mM Rat liver
K_{m}^{UTP} 16[4] mM Rat tissue
K_{m}^{UDP} 0.19[3] mM Rat liver
K_{eq} 1 Dimensionless

Parameters with uncertainty

  • In the paper by Walter (1980) et. al. [3] two values of K_{m}^{ADP}, K_{m}^{ATP} and K_{m}^{UDP} have been reported; one for cytosolic kinase and the other for membrane-associated kinase. As in our model we are not differentiating between cytosolic and membrane-associated kinase, we would consider both those values and calculate the uncertainty from them.
  • Similarly two values of K_{m}^{UTP} has been reported in Fukuchi (1994) et. al. [4]; for \alpha kinase and \beta kinase. Taking average of those kinase gives a value of 21.5 \pm 7.77
  • Two values of V_{max} is also reported in Fukuchi (1994) et. al. [4]; 126 (4.20 \text{mmol min}^{-1}\text{ mg}^{-1} multiplied with 30 mg) and 138 (4.60 \text{mmol min}^{-1}\text{ mg}^{-1} multiplied with 30 mg) \text{mmol min}^{-1}. Taking average gives 132 \pm 8.48.
  • Standard free energy \Delta G^{o}{'} is reported to be zero kJ/mol. Therefore the value of Keq can be assumed to be constant. As there was no reported other value std. dev. from other Keq values are considered which is Failed to parse (Cannot store math image on filesystem.): \approx 30% . So the Keq value would be Failed to parse (Cannot store math image on filesystem.): 1 \pm 0.3
Parameter Value Units Organism Remarks
V_{max} 132 \pm 8.48 min^{-1} Rat lever
K_{m}^{ATP}  1.49 \pm 0.23 mM
K_{m}^{ADP} 0.0575 \pm 0.02 mM
K_{m}^{UTP} 21.5 \pm 7.77 mM
K_{m}^{UDP} 0.17 \pm 0.02 mM
K_{eq} Failed to parse (Cannot store math image on filesystem.): 1 \pm .3 Dimensionless

References

  1. 1.0 1.1 M. König, S. Bulik, H.G. Holzhütter (2012), Quantifying the contribution of the liver to glucose homeostasis: a detailed kinetic model of human hepatic glucose metabolism, PLoS Comput. Biol., 8 (6), p. e1002577
  2. Villar-Palasi C & Larner J (1960). Levels of activity of the enzymes of the glycogen cycle in rat tissues. Arch Biochem Biophys 86, 270–273.
  3. 3.0 3.1 3.2 3.3 Walter P and Blobel G. (1980), Purification of a membrane-associated protein complex required for protein translocation across the endoplasmic reticulum, Proc. Natl. Acad. Sci. 77:7112-7116
  4. 4.0 4.1 4.2 Fukuchi, T., Shimada, N., Hanai, N., Ishikawa, N., Watanabe, K., and Kimura, N. (1994) Recombinant rat nucleoside diphosphate kinase isoforms (\alpha and \beta): purification, properties and application to immunological detection of native isoforms in rat tissues. Biochim. Biophys. Acta 1205, 113–122