Transformation of PGH2 to PGE2

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PGE2 is an incredibly bioactive compound, which upon binding with the receptors, an immune cellular response is triggered. For example in the binding of PGE2 to EP2 and EP4, dendritic cell (DC) migration and maturation is activated (Legler, Krause et al. 2006, van Helden, Krooshoop et al. 2006). This event results in the activation of Th2 cells, which produce cytokines that in turn stimulates further inflammatory species (McIlroy, Caron et al. 2006, Theiner, Gessner et al. 2006). Furthermore binding of PGE2 to EP4 stimulates infiltration of macrophages from the bloodstream.

PGE2 is synthesised from PGH2 via the prostaglandin E synthase (PGES) enzyme. This influential species is produced by almost all cutaneous cell types and as a consequence is in high concentrations in the skin (Ziboh 1992, Cho, Park et al. 2005, Gledhill, Rhodes et al. 2010). In addition to affecting DCs, the species acts as a chemoattractant for keratinocyte cells (Parekh, Sandulache et al. 2009) and in normal and inflamed epithelial cells PGE2 possess an inhibitory effect on the release of leukotrienes (Shaf96).

Reaction

Chemical equation

$PGH2 \rightleftharpoons PGE2$

Rate equation

Parameters

K_ms

Literature values

Value	Units	Species	Notes	Reference
1.6E-01 ± 4.00E-03	$mM$	Human	Expression Vector: E. Coli Enzyme: PGES pH: 8 Temperature: 37
2.15E-01	$mM$	Human	Wild Type Enzyme
1.49E-02	$mM$	Human	Expression Vector: E. Coli Enzyme: PGES pH: Unknown Temperature: Unknown Other: cPGES, casein kinase II and Hsp90
6.66E-02	$mM$	Human	Expression Vector: E. Coli Enzyme: PGES pH: Unknown Temperature: Unknown

Description of the PGES Kms distribution

Mode (mM)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
1.97E-01	1.73E+00	-1.39E+00	4.91E-01

The estimated probability distribution for PGES 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.

K_mp

This is a “Dependent parameter”, meaning that the log-normal distribution for this parameter was calculated using multivariate distributions (this is discussed in detail here). As a result, no confidence interval factor or literature values were cited for this parameter.

Description of the PGES Kmp distribution

Mode (mM)	Location parameter (µ)	Scale parameter (σ)
1.93E-01	-1.15E+00	7.02E-01 (mM)

The estimated probability distribution for PGES 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.

k_cat

Literature values

Value	Units	Species	Notes	Reference
3000 ± 360	per minute	Human	Expression Vector: E. Coli. Enzyme: Microsomal Prostaglandin E Synthase pH: 7.5 Temperature: 37

Description of the PGES kcat distribution

Mode (min-1)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
2.98E+03	1.13E+00	8.01E+00	1.19E-01

The estimated probability distribution for PGES 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	Reference
220	$ppm$	Human	Expression Vector: Placenta Enzyme: PGES pH: 7.5 Temperature: 37 °C
75.3	$ppm$	Human	Expression Vector: Urinary Bladder Enzyme: PGES pH: 7.5 Temperature: 37 °C
208	$ppm$	Human	Expression Vector: Stomach Enzyme: PGES pH: 7.5 Temperature: 37 °C
28.1	$ppm$	Human	Expression Vector: Lung Enzyme: PGES pH: 7.5 Temperature: 37 °C
11.6	$ppm$	Human	Expression Vector: Colon Enzyme: PGES pH: 7.5 Temperature: 37 °C

Description of the PGES concentration distribution

Mode	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
7.49E+01	3.15E+00	5.03E+00	8.44E-01

The estimated probability distribution for PGES 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.

K_eq

Gibbs Free Energy Change

Value	Units	Species	Notes	Reference
5.72	kcal/mol	Not stated	Estimated Enzyme: PGES Substrate: Arachidonate Product: PGE2 pH: 7.3 ionic strength: 0.25

Description of the PGES Keq distribution

Mode	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
7.46E+04	1.00E+01	1.20E+01	8.90E-01

The estimated probability distribution for PGES 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.

Related Reactions

• Transformation of AA to PGH2