Transformation of PGH2 to PGF2α

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The isomerisation of PGH2 to PGF2a is performed by PGFS. This reaction results in the formation of two hydroxyl groups at C9 and C11. This reaction takes place in the cytosol of cells and the cofactor is NADPH. PGFS is found to also catalyse the conversion of aldehydes and ketones to PGF2a, for example the conversion of PGD2 to PGF2a.

PGF2α has been found to be produced by keratinocyte cells in vitro (Rhodes, Gledhill et al. 2009). This species is synthesised from PGH2 via the prostaglandin F synthase (PGFS) or the PGE 9-ketoreductase enzymes. Upon production this species have been associated with pigmentation, inflammation and hair growth in the skin (Scott, Leopardi et al. 2004, Scott, Fricke et al. 2007). The species has various inflammatory roles such as a pro-inflammatory effect upon the system by facilitating pain transmission (Murata, Ushikubi et al. 1997) and also an anti-inflammatory effect by inhibiting lymphocyte and endothelial cell interactions (Della Bella, Molteni et al. 2001).

Reaction

Chemical equation

$PGH2 \rightleftharpoons PGF2a$

Rate equation

Parameters

K_ms

Literature values

Value	Units	Species	Notes	Reference
1.90E-03 ± 1.5E-03	$mM$	Human	Placental Aldose Reductase (AKR1B1), E. Coli, pH 7, 37°C
1.80E-02	$mM$	Human	Lung PGF2a Synthase (AKR1C3), E. Coli, pH 7, 37°C

Description of the PGFS Kms distribution

Mode (mM)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
1.33E-02	3.81E+00	-3.45E+00	9.33E-01

The estimated probability distribution for PGFS 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

In this model some parameters are referred as “Dependent parameters”, meaning that the log-normal distribution for that parameter was calculated using multivariate distributions (discussed in Protocol for defining informative priors for ensemble modelling in systems biology). As a result, no confidence interval factor or literature values were cited for the Dependent parameters.

Description of the PGFS Kmp distribution

Mode	Location parameter (µ)	Scale parameter (σ)
1.46E-02	-2.86E+00	1.17E+00

The estimated probability distribution for PGFS 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
14.9	per minute	Mouse/Swine	Prostamide/PGF Synthase Purified from Swine Brain and of Murine Enzyme Expressed in E. coli

Description of the PGFS kcat distribution

Mode (min-1)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
1.48E+01	1.10E+00	2.71E+00	9.49E-02

The estimated probability distribution for PGFS 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
105	$ppm$	Human	Expression Vector: Platelet Enzyme: PGFS pH: 7.5 Temperature: 37 °C
19.9	$ppm$	Human	Expression Vector: Lung Enzyme: PGFS pH: 7.5 Temperature: 37 °C
40.3	$ppm$	Human	Expression Vector: Esophagus Enzyme: PGFS pH: 7.5 Temperature: 37 °C
110	$ppm$	Human	Expression Vector: Oral Cavity Enzyme: PGFS pH: 7.5 Temperature: 37 °C

Description of the PGFS concentration distribution

Mode (mM)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
6.41E+01	2.05E+00	4.53E+00	6.06E-01

The estimated probability distribution for PGFS 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.

Related Reactions

• Transformation of AA to PGH2