Transformation of PGE2 to 15-Keto-PGE2
The primary catabolic pathway of prostanoids is initiated by the oxidation of the C15 hydroxyl group by 15-prostoglandin dehydrogenase (15-PGDH). 15-PGDH can accept a wide variety of prostaglandins as substrates. Two isoforms of 15-PGDH have been recognised, Type I is NAD+ specific, whereas Type II prefers NADP+. 15-PGDH Type I is prostaglandin and lipoxin specific, whereas Type II exhibits broad substrate specificity, therefore Type I is typically referred to as 15-PGDH in the literature [1][2].
Contents
Reaction
Chemical equation
Rate equation
Enzyme Parameters
Kms
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
0.008 | Rat Skin | Method:
pH:7.4 Temperature: 37'C Substrate: PGE2 + NAD+ |
1024 | [3] | |
0.0075 | Rat Skin | Method:
pH:7.4 Temperature: 37'C Substrate: PGE2 + NADP+ |
1024 | [3] | |
0.024 | Rat Skin | Method:
pH:7.4 Temperature: 37'C Substrate: PGF2a + NAD+ |
1024 | [3] | |
0.023 | Rat Skin | Method:
pH:7.4 Temperature: 37'C Substrate: PGF2a + NADP+ |
1024 | [3] | |
0.0039 | Purified Human 15-PGDH | Method: In vitro
Expression Vector: E. coli pH:7.5 Temperature: 37'C Substrate: PGE2 |
1024 | [4] | |
0.0099 | Purified Rat 15-PGDH | Method: In vitro
Expression Vector: E. coli pH:7.5 Temperature: 37'C Substrate: PGE2 |
512 | [4] | |
0.0055 ± 0.0006 | Human | Method:In vitro
Expression Vector: E. Coli pH:8 Temperature: 25 Substrate: PGE2 + NAD+ |
1024 | [5] |
Mode (mM) | Confidence Interval | Location parameter (μ) | Scale parameter (σ) |
---|---|---|---|
7.64E-03 | 5.05E+00 | -4.41E+00 | 6.80E-01 |
Kmp
Mode (mM) | Location parameter (μ) | Scale parameter (σ) |
---|---|---|
7.70E-03 | -4.41E+00 | 6.72E-01 |
kcat
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
816 ± 18 | Human | Method: In vitro
Expression Vector: E. Coli pH:8 Temperature: 25 Substrate: PGE2 + NAD+ |
128 | [5] | |
366 ± 12 - 846 ± 12 | Human | Method: In vitro
Expression Vector: E. Coli pH:8 Temperature: 25 Substrate: PGE2 + NAD+ + Inhibitor |
128 | [5] |
Mode (min-1) | Confidence Interval | Location parameter (μ) | Scale parameter (σ) |
---|---|---|---|
8.12E+02 | 5.38E+00 | 7.19E+00 | 7.01E-01 |
Enzyme concentration
To convert the enzyme concentration from ppm to mM, the following equation was used.
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
69.8 | Human | Expression Vector: Esophagus
Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C |
1024 | [6] | |
22.1 | Human | Expression Vector: Heart
Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C |
1024 | [7] | |
11.2 | Human | Expression Vector: Esophagus
Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C |
1024 | [7] | |
7.68 | Human | Expression Vector: Skin
Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C |
2048 | Paxdb - Unknown |
Mode (ppm) | Mode (mM) | Confidence Interval | Location parameter (μ) | Scale parameter (σ) |
---|---|---|---|---|
1.12E+01 | 6.20E-05 | 2.32E+00 | 2.87E+00 | 6.80E-01 |
Keq
Value | Units | Species | Notes | Weight | Reference |
---|---|---|---|---|---|
(-0.46818542) | kcal/mol | Calculated | Estimated
Enzyme: 15-PGDH Substrate: PGE2 Product: 15-dehydro-PGE2 pH: 7.3 ionic strength: 0.25 |
64 | [8] |
Mode | Confidence Interval | Location parameter (μ) | Scale parameter (σ) |
---|---|---|---|
2.21E+00 | 1.00E+01 | 1.58E+00 | 8.91E-01 |
References
- ↑ Ensor, C. M. Tai, H. H., 15-Hydroxyprostaglandin dehydrogenase, J Lipid Mediat Cell Signal (1995), 12, 313-9.
- ↑ Wermuth, B., Purification and properties of an NADPH-dependent carbonyl reductase from human brain. Relationship to prostaglandin 9-ketoreductase and xenobiotic ketone reductase, J Biol Chem (1981), 256, 1206-13.
- ↑ 3.0 3.1 3.2 3.3 N. Fincham, Novel prostaglandin dehydrogenase in rat skin. Biochem J. 1983 Apr 15;212(1):129-34.
- ↑ 4.0 4.1 Zhou H., C-Terminal region of human NAD+-dependent 15-hydroxyprostaglandin dehydrogenase is involved in the interaction with prostaglandin substrates. Eur J Biochem. 2001 Jun;268(12):3368-74.
- ↑ 5.0 5.1 5.2 F. Niesen,, High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships PLoS One. 2010 Nov 2;5(11):e13719.
- ↑ M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
- ↑ 7.0 7.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
- ↑ Caspi et al 2014, "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases," Nucleic Acids Research 42:D459-D471