6-phosphogluconate dehydrogenase

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6-phosphogluconate dehydrogenase is the third enzyme of the Pentose Phosphate pathway. It catalyses the oxidative decarboxylation of 6-phosphogluconate using NADP+. The product of this reaction is ribulose 5-P, CO2 and NADPH. This is the second step of the pentose phosphate pathway producing NADPH and the last step of the oxidative phase.

Chemical reaction

6-PGA + NADP^+ \rightleftharpoons Rbu-5-P + NADPH + CO_{2}

Rate equation

The basic reaction mechanism can be modelled with an ordered Bi-ter equation [1]


v=\frac{V_{max}*[NADP^+]*[6-PGA]}{k_{iNADP}*k_{6-PGA}+k_{6-PGA}*[NADP^+]+k_{NADP^+}*[6-PGA]+[NADP^+]*[6-PGA]}

Parameters values

Name Value Units Organism Remarks
Km 6-PGA 0.0292[1] mM Pig liver
0.051±0.021[2] mM Recombinant human protein
0.063±0.004[2] mM Recombinant human protein
0.06±0.005[2] mM Recombinant human protein
0.016±0.0008[2] mM Human liver
0.023±0.0001[2] mM Human erythrocyte
0.041[2] mM Human Brain
Km NADP 0.0135[1] mM Pig liver
0.018±0.0008[2] mM Recombinant human protein
0.025 ± 0.001[2] mM Recombinant human protein
0.022 ± 0.0004[2] mM Recombinant human protein
0.0037[2] mM Human Brain
Vmax 0.00493*10-3[1] mM/min Pig liver
Kcat 73 ± 19[2] Recombinant human protein
57 ± 2[2] Recombinant human protein
44 ± 4[2] Recombinant human protein
21 ± 0.07[2] Human liver
21.3 ± 0.01[2] Human erythrocyte
Ki NADP 0.0048 ± 0.0008[1] mM Pig liver

Parameters with uncertainity

To cover the uncertainity inside cancer cells, the Km for 6PGA ad NADP were calculated using in vivo and in vitro measures. This information has been taken from Barden et al, 2013[2]. Th average Kcat was calculated in the same way, taking in account in vivo and in vitro values.

Name Value Units Organism Remarks
Km 6PGA 0.042 ± 0.019 mM Human
Km NADP 0.017 ± 0.0094 mM Human
Kcat 48.75 ± 21.98 s-1 Human

References

  1. 1.0 1.1 1.2 1.3 1.4 Toews, Myron L., M. I. Kanji, and W. R. Carper. "6-Phosphogluconate dehydrogenase. Purification and kinetics." Journal of Biological Chemistry 251.22 (1976): 7127-7131. ([1])
  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 2.12 2.13 2.14 2.15 Barden Chan, Vikas P. Sukhatme, One-step purification of soluble recombinant human 6-phosphogluconate dehydrogenase from Escherichia coli, Protein Expression and Purification, Volume 92, Issue 1, November 2013, Pages 62-66, ISSN 1046-5928 ([2])