Transformation of PGE2 to 15-Keto-PGE2

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15-hydroxyprostaglandin dehydrogenase, also known as (15-PGDH) metabolises PG into the 15-Keto variant via the oxidation of 15(S)-hydroxyl group. The enzyme is constituently expressed in the skin (Finhelm1982) and within the eicosanoid network it is reported as metabolising PGE2 and PGF2a.

It should be noted that Judson et al found that 15-PGDH expression of the enzyme decreases in response to UVR (Judson2010).


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 [1]
0.0075  mM Rat Skin Method:

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

1024 [1]
0.024  mM Rat Skin Method:

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

1024 [1]
0.023  mM Rat Skin Method:

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

1024 [1]
0.0039  mM Purified Human 15-PGDH Method: In vitro

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

1024 [2]
0.0099  mM Purified Rat 15-PGDH Method: In vitro

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

512 [2]
0.0055 ± 0.0006  mM Human Method:In vitro

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

1024 [3]
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 [3]
366 ± 12 - 846 ± 12  per minute Human Method: In vitro

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

128 [3]
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

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 [4]
22.1  ppm Human Expression Vector: Heart

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

1024 [5]
11.2  ppm Human Expression Vector: Esophagus

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

1024 [5]
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 (mM) Confidence Interval Location parameter (μ) Scale parameter (σ)
1.12E+01 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 [6]
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