Difference between revisions of "Glucose-6-Phosphate Dehydrogenase"
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==Rate equation== | ==Rate equation== | ||
The enzyme activity can be modelled with the Rapid Equilibrium Ordered Bi Bi equation <ref name="OAO_2001"> Nazmi Özer, Yasemin Aksoy, I.Hamdi Ögüs, Kinetic properties of human placental glucose-6-phosphate dehydrogenase, The International Journal of Biochemistry & Cell Biology, Volume 33, Issue 3, March 2001, Pages 221-226, ISSN 1357-2725, ([http://dx.doi.org/10.1016/S1357-2725(01)00011-5]) </ref> | The enzyme activity can be modelled with the Rapid Equilibrium Ordered Bi Bi equation <ref name="OAO_2001"> Nazmi Özer, Yasemin Aksoy, I.Hamdi Ögüs, Kinetic properties of human placental glucose-6-phosphate dehydrogenase, The International Journal of Biochemistry & Cell Biology, Volume 33, Issue 3, March 2001, Pages 221-226, ISSN 1357-2725, ([http://dx.doi.org/10.1016/S1357-2725(01)00011-5]) </ref> | ||
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| + | <center><math>v= \frac{V_{max}}{1+\frac{K_{mNADP}}{[NADP]}+\frac{K_{mG6P}}{[G6P]}+\frac{K_{mNADP}*K_{mG6P}}{[G6P]*[NADP]}}</math></center> | ||
==Parameters== | ==Parameters== | ||
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| Km NADP||0.01<ref name="PRP_2012"> Preuss, J., Richardson, A. D., Pinkerton, A., Hedrick, M., Sergienko, E., Rahlfs, S., ... & Bode, L. (2012). Identification and characterization of novel human glucose-6-phosphate dehydrogenase inhibitors. Journal of biomolecular screening, 1087057112462131. ([http://jbx.sagepub.com/content/18/3/286]) </ref>||mM||Mammary carcinoma|| | | Km NADP||0.01<ref name="PRP_2012"> Preuss, J., Richardson, A. D., Pinkerton, A., Hedrick, M., Sergienko, E., Rahlfs, S., ... & Bode, L. (2012). Identification and characterization of novel human glucose-6-phosphate dehydrogenase inhibitors. Journal of biomolecular screening, 1087057112462131. ([http://jbx.sagepub.com/content/18/3/286]) </ref>||mM||Mammary carcinoma|| | ||
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| − | | | + | | Vm||87<ref name="Y_1966"> Nazmi Özer, Yasemin Aksoy, I.Hamdi Ögüs, Kinetic properties of human placental glucose-6-phosphate dehydrogenase, The International Journal of Biochemistry & Cell Biology, Volume 33, Issue 3, March 2001, Pages 221-226, ISSN 1357-2725, ([http://dx.doi.org/10.1016/S1357-2725(01)00011-5]) </ref>||U*mg-1*protein||Human placenta|| |
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Latest revision as of 11:55, 9 July 2014
The glucose 6-phosphate dehydrogenase is the first and most important enzyme in the oxidative branch of the Pentose Phosphate pathway. There are 140 variants and its deficiency is linked to health problems [1]. It uses glucose 6-phosphate produced in the glycolysis and oxidizes it with NADP+. The result of the reaction is 6-phosphogluconolactone and NADPH, reduced form of NADP+. The whole process takes place in the cytoplasm.
Contents
Chemical equation
Rate equation
The enzyme activity can be modelled with the Rapid Equilibrium Ordered Bi Bi equation [2]
![v= \frac{V_{max}}{1+\frac{K_{mNADP}}{[NADP]}+\frac{K_{mG6P}}{[G6P]}+\frac{K_{mNADP}*K_{mG6P}}{[G6P]*[NADP]}}](/wiki/images/math/7/4/8/74838a72505759094511c80e104765ba.png)
Parameters
| Name | Value | Units | Organism | Remarks |
| KmG6P | 0.04[3] | mM | Human placenta | |
| 0.039[2] | mM | Human Erythrocyte | ||
| 0.095 – 0.120 [4] | mM | Mammary carcinoma | ||
| 0.0458±0.0016[5] | mM | Human Erythrocyte | ||
| 0.0444±0.0021[5] | mM | Plymouth mutant | ||
| 0.0507±0.0008[5] | mM | Mahidol mutant | ||
| 0.052[6] | mM | Human Erythrocyte | ||
| 0.0671±0.013[6] | mM | Wisconsin mutant | ||
| 0.19±0.027[6] | mM | Nashville mutant | ||
| 0.026-0.090[7] | mM | Human Erythrocyte | ||
| Km NADP | 0.02[3] | mM | Human placenta | |
| 0.0044[2] | mM | Human Erythrocyte | ||
| 0.01[4] | mM | Mammary carcinoma | ||
| 0.00467±0.000032[5] | mM | Human Erythrocyte | ||
| 0.0048±0.00041[5] | mM | Plymouth mutant | ||
| 0.00646±0.00027[5] | mM | Mahidol mutant | ||
| 0.00707[6] | mM | Human Erythrocyte | ||
| 0.00931±0.0024[6] | mM | Wisconsin mutant | ||
| 0.0165±0.0027[6] | mM | Nashville mutant | ||
| 0.008[7] | mM | Human Erythrocyte | ||
| Kcat | 251[5] | s-1 | Human Erythrocyte | |
| 249[5] | s-1 | Plymouth mutant | ||
| 207[5] | s-1 | Mahidol mutant | ||
| 275[6] | s-1 | Human Erythrocyte | ||
| 232[6] | s-1 | Wisconsin mutant | ||
| 192[6] | s-1 | Nashville mutant | ||
| Vm | 87[3] | U*mg-1*protein | Human placenta | |
| Ki NADPH | 0.0171±0.0032[3] | mM | Human placenta |
Parameters with uncertainity
Glucose 6-phosphate dehydrogenase is a highly polimorfic enzyme with more than 140 mutants reported[8]. It supplies with pentose sugars to the cell, neccesary to synthesise new DNA, among other things. This make it a crucial enzyme for cancer growth. The values for KmG6P and KmNADP used in this model are those coming from mammary carcinoma tissue. The Vmax value comes from a tissue with high metabolic activity, human placenta.
| Name | Value | Units | Organism | Remarks |
| Km G6P | 0.095 – 0.120[4] | mM | Mammary carcinoma | |
| Km NADP | 0.01[4] | mM | Mammary carcinoma | |
| Vm | 87[3] | U*mg-1*protein | Human placenta | |
References
- ↑ E. Beutler, T.J. Vulliamy, Hematologically important mutations: glucose-6-phosphate dehydrogenase, Blood Cells Mol. Diseases, 28 (2002), pp. 93–103 ([1])
- ↑ 2.0 2.1 2.2 Nazmi Özer, Yasemin Aksoy, I.Hamdi Ögüs, Kinetic properties of human placental glucose-6-phosphate dehydrogenase, The International Journal of Biochemistry & Cell Biology, Volume 33, Issue 3, March 2001, Pages 221-226, ISSN 1357-2725, ([2]) Cite error: Invalid
<ref>tag; name "OAO_2001" defined multiple times with different content Cite error: Invalid<ref>tag; name "OAO_2001" defined multiple times with different content - ↑ 3.0 3.1 3.2 3.3 3.4 Nazmi Özer, Yasemin Aksoy, I.Hamdi Ögüs, Kinetic properties of human placental glucose-6-phosphate dehydrogenase, The International Journal of Biochemistry & Cell Biology, Volume 33, Issue 3, March 2001, Pages 221-226, ISSN 1357-2725, ([3])
- ↑ 4.0 4.1 4.2 4.3 Preuss, J., Richardson, A. D., Pinkerton, A., Hedrick, M., Sergienko, E., Rahlfs, S., ... & Bode, L. (2012). Identification and characterization of novel human glucose-6-phosphate dehydrogenase inhibitors. Journal of biomolecular screening, 1087057112462131. ([4])
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 5.7 5.8 Yuxiang Huang, Mei Yee Choi, Shannon Wing Ngor Au, Deborah Man Yee Au, Veronica Min Sien Lam, Paul C. Engel, Purification and detailed study of two clinically different human glucose 6-phosphate dehydrogenase variants, G6PDPlymouth and G6PDMahidol: Evidence for defective protein folding as the basis of disease, Molecular Genetics and Metabolism, Volume 93, Issue 1, January 2008, Pages 44-53, ISSN 1096-7192 ([5])
- ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 Xiao-Tao Wang, Veronica M.S. Lam, Paul C. Engel, Functional properties of two mutants of human glucose 6-phosphate dehydrogenase, R393G and R393H, corresponding to the clinical variants G6PD Wisconsin and Nashville, Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Volume 1762, Issue 8, August 2006, Pages 767-774, ISSN 0925-4439([6])
- ↑ 7.0 7.1 L. Luzzatto, A. Afolayan, Enzymic properties of different types of human erythrocyte glucose-6-phosphate dehydrogenase, with characterization of two new genetic variants, J Clin Invest. 1968 August; 47(8): 1833–1842. ([7])
- ↑ Ernest Beutler, Tom J Vulliamy, Hematologically Important Mutations: Glucose-6-phosphate Dehydrogenase, Blood Cells, Molecules, and Diseases, Volume 28, Issue 2, March 2002, Pages 93-103, ISSN 1079-9796, ([8])
