Transformation of PGE2 to 15-Keto-PGE2

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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].

Reaction

R66 15PGDH.jpg

Chemical equation

 PGE2 \rightleftharpoons 15-Keto-PGE2

Rate equation

R66.PNG

Enzyme Parameters

Kms

Literature values
Value Units Species Notes Weight Reference
0.008  mM Rat Skin Method:

pH:7.4 Temperature: 37'C Substrate: PGE2 + NAD+

1024 [3]
0.0075  mM Rat Skin Method:

pH:7.4 Temperature: 37'C Substrate: PGE2 + NADP+

1024 [3]
0.024  mM Rat Skin Method:

pH:7.4 Temperature: 37'C Substrate: PGF2a + NAD+

1024 [3]
0.023  mM Rat Skin Method:

pH:7.4 Temperature: 37'C Substrate: PGF2a + NADP+

1024 [3]
0.0039  mM Purified Human 15-PGDH Method: In vitro

Expression Vector: E. coli pH:7.5 Temperature: 37'C Substrate: PGE2

1024 [4]
0.0099  mM 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  mM Human Method:In vitro

Expression Vector: E. Coli pH:8 Temperature: 25 Substrate: PGE2 + NAD+

1024 [5]
Description of the 15-PGDH Kms distribution
Mode (mM) Confidence Interval Location parameter (μ) Scale parameter (σ)
7.64E-03 5.05E+00 -4.41E+00 6.80E-01
The estimated probability distribution for 15-PGDH Kms. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

Kmp

Description of the 15-PGDH Kmp distribution
Mode (mM) Location parameter (μ) Scale parameter (σ)
7.70E-03 -4.41E+00 6.72E-01
The estimated probability distribution for 15-PGDH Kmp. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

kcat

Literature values
Value Units Species Notes Weight Reference
816 ± 18  per minute Human Method: In vitro

Expression Vector: E. Coli pH:8 Temperature: 25 Substrate: PGE2 + NAD+

128 [5]
366 ± 12 - 846 ± 12  per minute Human Method: In vitro

Expression Vector: E. Coli pH:8 Temperature: 25 Substrate: PGE2 + NAD+ + Inhibitor

128 [5]
Description of the 15-PGDH kcat distribution
Mode (min-1) Confidence Interval Location parameter (μ) Scale parameter (σ)
8.12E+02 5.38E+00 7.19E+00 7.01E-01
The estimated probability distribution for 15-PGDH kcat. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

Enzyme concentration

To convert the enzyme concentration from ppm to mM, the following equation was used.

Literature values
Value Units Species Notes Weight Reference
69.8  ppm Human Expression Vector: Esophagus

Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C

1024 [6]
22.1  ppm Human Expression Vector: Heart

Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C

1024 [7]
11.2  ppm Human Expression Vector: Esophagus

Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C

1024 [7]
7.68  ppm Human Expression Vector: Skin

Enzyme: 15-PGDH pH: 7.5 Temperature: 37 °C

2048 Paxdb - Unknown
Description of the 15-PGDH concentration distribution
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
The estimated probability distribution for 15-PGDH concentration. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

Keq

Gibbs Free Energy Change
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]
Description of the 15-PGDH Keq distribution
Mode Confidence Interval Location parameter (μ) Scale parameter (σ)
2.21E+00 1.00E+01 1.58E+00 8.91E-01
The estimated probability distribution for 15-PGDH Keq. The value and weight of the literature values used to define the distribution are indicated by an orange dashed line. The x axis is plotted on a log-scale.

References