Transformation of 15-Keto-PGE2 to 13,14-Dihydro-15-Keto-PGE2
The second step of the catabolic pathway of prostanoids is the reduction of the conjugated α, β-unsaturated double bond at C13, by 13, 15-ketoprostglandin reductase, also known as prostaglandin reductase. There are two isoforms of this protein, prostaglandin reductase 1 (PTGR-1) and prostaglandin reductase 2 (PTGR-2). Prostaglandin reductase 1 (PTGR-1) can accept a wide variety of prostaglandins as substrates. Prostaglandin reductase 2 (PTGR-2) has the highest affinity for 15-keto-PGE2, but also accepts a wide variety of prostaglandins as a substrate [1].
Contents
Reaction
Chemical equation
Rate equation
Parameters
Kms
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
0.01121 ± 0.00014 | mM | Human | Method: In vitro
Organism: Human Expression vector: E.coli Enzyme: PTGR2 pH: 7.5 Temperature: 37 ◦C Substrate: 15-Keto-PGE2 "For determining the KM and Vmax values for NADPH, 15-keto-PGE2 at a final concentration of 200 mM was used with different concentrations of NADPH (0–60 mM)." |
512 | [2] |
0.01587 ± 0.00171 | mM | Human | Method: In vitro
Organism: Human Expression vector: E.coli Enzyme: e PTGR2 pH: 7.5 Temperature: 37 ◦C Substrate: NADPH "For determining the KM and Vmax values for NADPH, 15-keto-PGE2 at a final concentration of 200 mM was used with different concentrations of NADPH (0–60 mM)." |
512 | [2] |
Mode (mM) | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
1.20E-02 | 4.92E+00 | -3.97E+00 | 6.71E-01 |
Kmp
Mode (mM) | Location parameter (µ) | Scale parameter (σ) |
---|---|---|
1.19E-02 | -3.97E+00 | 6.81E-01 |
kcat
Note: Turnover values from EC 1.3.1.48 - 13,14-dehydro-15-oxoprostaglandin 13-reductase
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
11.4 ± 0.9 | min-1 | Mouse | Method: In vitro
Organism: Mouse Expression vector: Enzyme: 13,14-dehydro-15-oxoprostaglandin 13-reductase pH: 7.4 Temperature: 37 ◦C Substrate: 15-Ketoprostaglandin E2 |
384 | [2] |
Mode (min-1) | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
1.14E+01 | 9.86E+00 | 3.22E+00 | 8.87E-01 |
Enzyme concentration
To convert the enzyme concentration from ppm to mM, the following equation was used.
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
162 | ppm | Human | Expression Vector: Skin
Enzyme: PTGR2 pH: 7.5 Temperature: 37 °C |
2048 | [3] |
80.9 | ppm | Human | Expression Vector: Skin
Enzyme: PTGR2 pH: Unknown Temperature: Unknown |
2048 | Unknown |
74.1 | ppm | Human | Expression Vector: Oral Cavity
Enzyme: PTGR2 pH: 7.5 Temperature: 37 °C |
1024 | [3] |
Mode (ppm) | Mode (mM) | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|---|
8.65E+01 | 4.79E-04 | 1.45E+00 | 4.58E+00 | 3.47E-01 |
Keq
Gibbs Free energy | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
3.6006165 | kcal/mol | Unspecified | Calculations with a Gaussian98 suite of programs
Enzyme: COX (Unspecific) Substrate: Arachidonate Temperature: 298.15 K Pressure: 1 bar |
64 | [4] |
Mode | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
2.28E-03 | 1.00E+01 | -5.29E+00 | 8.91E-01 |
Misch
Value | Units | Species | Notes | Reference |
---|---|---|---|---|
9.9 +/-0.2 | minutes | Dog | In vivo
Temperature:37 pH:7 |
[5] |
Value | Units | Species | Notes | Reference |
---|---|---|---|---|
159.23 ± 0.71 | nmol min-1 mg-1 | Human | Method: In vitro
Organism: Human Expression vector: E.coli Enzyme: PTGR2 pH: 7.5 Temperature: 37 ◦C Substrate: 15-Keto-PGE2 |
[2] |
66.73 ± 1.36 | nmol min-1 mg-1 | Human | Method: In vitro
Organism: Human Expression vector: E.coli Enzyme: PTGR2 pH: 7.5 Temperature: 37 ◦C Substrate: NADPH |
[2] |
References
- ↑ Wu, Yu-Hauh Ko, Tzu-Ping Guo, Rey-Ting Hu, Su-Ming Chuang, Lee-Ming Wang, Andrew H J., Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2,Structure (2008), 16, 1714-1723.
- ↑ 2.0 2.1 2.2 2.3 2.4 "Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2", Structure. 2008 Nov 12;16(11):1714-23. doi: 10.1016/j.str.2008.09.007.
- ↑ 3.0 3.1 [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587]
- ↑ P. Silva, "A theoretical study of radical-only and combined radical/carbocationic mechanisms of arachidonic acid cyclooxygenation by prostaglandin H synthase" Theor Chem Acc (2003) 110: 345
- ↑ W. Bothwell, "A radioimmunoassay for the unstable pulmonary metabolites of prostaglandin E1 and E2: an indirect index of their in vivo disposition and pharmacokinetics" Journal of Pharmacology and Experimental Therapeutics February 1982, 220 (2) 229-235