Difference between revisions of "Nucleosid diphosphate kinase"
(21 intermediate revisions by the same user not shown) | |||
Line 1: | Line 1: | ||
+ | [[Category:Uncertainty]] | ||
'''Nucleoside-diphosphate kinase'''s 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. | '''Nucleoside-diphosphate kinase'''s 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. | ||
Line 5: | Line 6: | ||
==Rate equation== | ==Rate equation== | ||
− | Random order Bi-Bi rate law is used | + | Random order Bi-Bi rate law is used from <ref name="Konig_2012">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</ref> |
− | <center><math>\frac{ \frac{V_{max}}{K_m^{ATP}K_m^{UDP}}\left( [ATP][UDP] - \frac{[ADP][UTP]}{K_{eq}} \right) } {1}</math></center> | + | <center><math>\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 }</math></center> |
+ | |||
+ | |||
+ | ==Parameter values== | ||
+ | * A mean body weight is defined as 75Kg in Konig et. al <ref name="Konig_2012"></ref>. The <math>V_{max}</math> is calculated by multiplying the reported value with body weight. | ||
+ | |||
+ | {|class="wikitable" | ||
+ | ! Parameter | ||
+ | ! Value | ||
+ | ! Units | ||
+ | ! Organism | ||
+ | ! Remarks | ||
+ | |- | ||
+ | |<math>V_{max}</math> | ||
+ | |<math>131.25</math> <ref name = "villar_1960"> 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.</ref> | ||
+ | |<math>min^{-1}</math> | ||
+ | |Human Liver | ||
+ | |rowspan="6"| | ||
+ | |- | ||
+ | |<math>K_{m}^{ATP}</math> | ||
+ | |<math> 1.33 </math><ref name="Walter_1980">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</ref> | ||
+ | |mM | ||
+ | |Rat liver | ||
+ | |- | ||
+ | |<math>K_{m}^{ADP}</math> | ||
+ | |<math>0.042</math><ref name="Walter_1980"></ref> | ||
+ | |mM | ||
+ | |Rat liver | ||
+ | |- | ||
+ | |<math>K_{m}^{UTP}</math> | ||
+ | |<math>16</math><ref name="Fukuchi_1994"> Fukuchi, T., Shimada, N., Hanai, N., Ishikawa, N., Watanabe, K., and Kimura, N. (1994) ''Recombinant rat nucleoside diphosphate kinase isoforms (<math>\alpha</math> and <math>\beta</math>): purification, properties and application to immunological detection of native isoforms in rat tissues. Biochim. Biophys. Acta 1205, 113–122</ref> | ||
+ | |mM | ||
+ | |Rat tissue | ||
+ | |- | ||
+ | |<math>K_{m}^{UDP}</math> | ||
+ | |<math>0.19</math><ref name="Walter_1980"></ref> | ||
+ | |mM | ||
+ | |Rat liver | ||
+ | |- | ||
+ | |<math>K_{eq}</math> | ||
+ | |<math>1</math> | ||
+ | |Dimensionless | ||
+ | | | ||
+ | |} | ||
+ | |||
+ | ==Parameters with uncertainty== | ||
+ | * In the paper by Walter (1980) et. al. <ref name="Walter_1980"></ref> two values of <math>K_{m}^{ADP}</math>, <math>K_{m}^{ATP}</math> and <math>K_{m}^{UDP}</math> 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 <math>K_{m}^{UTP}</math> has been reported in Fukuchi (1994) et. al. <ref name="Fukuchi_1994"></ref>; for <math>\alpha</math> kinase and <math>\beta</math> kinase. Taking average of those kinase gives a value of <math>21.5 \pm 7.77</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>. <br>'''Note:''' This <math>V_{max}</math> value fails to reach a Steady-State for our model. Therefore we collected the <math>V_{max}</math> for ''Saccharomyces cerevisiae'' from Jong(1991) et. al. <ref name="Jong_1990"> Ambrose Y. Jong, Jin. J. Ma (1991), ''Saccharomyces cerevisiae nucleoside-diphosphate kinase: Purification, characterization, and substrate specificity'', Archives of Biochemistry and Biophysiscs, Vol. 291, No. 2, pp. 241-246</ref> which is <math>8.5 \times 10^{-6}</math>. But the value does not report any uncertainty. We took the largest Relative percente error of <math>V_{max}</math> in the model. Which is <math>71%</math>. Therefore the value with uncertainty becomes <math> 8.5 \times 10^{-6} \pm 6.04 \times 10^{-6} </math> | ||
+ | |||
+ | *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 other value reported, Std. Dev. from transporter Keq values are considered which is <math>\approx 70%</math>. So the Keq value would be <math>1 \pm 0.7</math> | ||
+ | |||
+ | {|class="wikitable" | ||
+ | ! Parameter | ||
+ | ! Value | ||
+ | ! Units | ||
+ | ! Organism | ||
+ | ! Remarks | ||
+ | |- | ||
+ | |<math>V_{max}</math> | ||
+ | |<math>8.5 \times 10^{-6} \pm 6.04 \times 10^{-6}</math> | ||
+ | |<math>min^{-1}</math> | ||
+ | |rowspan="6"|Rat lever | ||
+ | |rowspan="6"| | ||
+ | |- | ||
+ | |<math>K_{m}^{ATP}</math> | ||
+ | |<math> 1.49 \pm 0.23 </math> | ||
+ | |mM | ||
+ | |- | ||
+ | |<math>K_{m}^{ADP}</math> | ||
+ | |<math>0.0575 \pm 0.02</math> | ||
+ | |mM | ||
+ | |- | ||
+ | |<math>K_{m}^{UTP}</math> | ||
+ | |<math>21.5 \pm 7.77</math> | ||
+ | |mM | ||
+ | |- | ||
+ | |<math>K_{m}^{UDP}</math> | ||
+ | |<math>0.17 \pm 0.02</math> | ||
+ | |mM | ||
+ | |- | ||
+ | |<math>K_{eq}</math> | ||
+ | |<math>1 \pm 0.7</math> | ||
+ | |Dimensionless | ||
+ | |} | ||
+ | |||
+ | ==References== | ||
+ | <references/> |
Latest revision as of 11:38, 17 July 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.
Contents
Chemical equation
Rate equation
Random order Bi-Bi rate law is used from [1]
Parameter values
- A mean body weight is defined as 75Kg in Konig et. al [1]. The is calculated by multiplying the reported value with body weight.
Parameter | Value | Units | Organism | Remarks |
---|---|---|---|---|
[2] | Human Liver | |||
[3] | mM | Rat liver | ||
[3] | mM | Rat liver | ||
[4] | mM | Rat tissue | ||
[3] | mM | Rat liver | ||
Dimensionless |
Parameters with uncertainty
- In the paper by Walter (1980) et. al. [3] two values of , and 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 has been reported in Fukuchi (1994) et. al. [4]; for kinase and kinase. Taking average of those kinase gives a value of
- Two values of is also reported in Fukuchi (1994) et. al. [4]; 126 (4.20 multiplied with 30 mg) and 138 (4.60 multiplied with 30 mg) . Taking average gives .
Note: This value fails to reach a Steady-State for our model. Therefore we collected the for Saccharomyces cerevisiae from Jong(1991) et. al. [5] which is . But the value does not report any uncertainty. We took the largest Relative percente error of in the model. Which is . Therefore the value with uncertainty becomes
- Standard free energy is reported to be zero kJ/mol. Therefore the value of Keq can be assumed to be constant. As there was no other value reported, Std. Dev. from transporter Keq values are considered which is . So the Keq value would be
Parameter | Value | Units | Organism | Remarks |
---|---|---|---|---|
Rat lever | ||||
mM | ||||
mM | ||||
mM | ||||
mM | ||||
Dimensionless |
References
- ↑ 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
- ↑ 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.
- ↑ 3.0 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
- ↑ 4.0 4.1 4.2 Fukuchi, T., Shimada, N., Hanai, N., Ishikawa, N., Watanabe, K., and Kimura, N. (1994) Recombinant rat nucleoside diphosphate kinase isoforms ( and ): purification, properties and application to immunological detection of native isoforms in rat tissues. Biochim. Biophys. Acta 1205, 113–122
- ↑ Ambrose Y. Jong, Jin. J. Ma (1991), Saccharomyces cerevisiae nucleoside-diphosphate kinase: Purification, characterization, and substrate specificity, Archives of Biochemistry and Biophysiscs, Vol. 291, No. 2, pp. 241-246