Welcome to the In-Silico Model of Cutaneous Lipids Wiki

About the Project

The skin is the largest structure in the body and acts as the ultimate barrier to our environment. The aim of this project is to comprehend how the lipid network within the skin responds in physiopathological states such as inflammation (sunburn, atopic dermatitis, psoriasis). Little is known about the regulatory relationships within the cutaneous lipid signalling networks, and there is a distinct lack of information about how these networks interact between compartments (the different layers of the skin).

Description of the Model

We aim to create a quantitative computational model of the cutaneous lipid signalling networks, including variables such as multiple lipid substrates and enzyme isoforms. Model construction will be guided by literature studies, combined with new experimental lipidomics data collected in this project. In order to analyse model properties, experimental studies such as altering the systemic availability of fatty acids and the effect upon the anti-inflammatory milieu will be measured. This information will be integrated into the model to obtain estimated kinetic parameter values and also to validate and refine the overall model topology. The resulting mathematical model will be testable and predictive of the lipid responses during inflammation. The insights obtained will allow for more targeted experiments to be designed in order to better understand skin lipid biology and to aid in the mapping of lipid networks contributing to inflammation. This will ultimately support the design of interventional studies to combat skin disease.

Error creating thumbnail: Unable to save thumbnail to destination

A detailed network of the stimulated arachidonic acid cascade in human skin cells. The metabolites are shown in green rectangles and the enzymes are shown in blue rectangles. The numbered arrows between the metabolites represent the reaction number. The arrows in bold represent the enzyme catalysed reactions, the normal arrows represent non-enzyme catalysed reactions. The degradation and extracellular transport reactions are not shown for simplification purposes. For the full names of the metabolites and enzymes please refere to the abbreviations list.

Reactions

The reactions per compartment are the following:

Transformation of PL to AA Prostanoids Transformation of AA to PGH2 Transformation of PGH2 to PGF2α Transformation of PGH2 to TXA2 Transformation of PGH2 to PGI2 Transformation of PGH2 to PGD2 Transformation of PGH2 to PGE2 Transformation of TXA2 to TXB2 Transformation of PGI2 to 6-K-PGF1α Transformation of PGD2 to PGJ2 Transformation of PGJ2 to 15-D-PGJ2 Mono and Poly Hydroxy Fatty Acids Transformation of AA to 5-HPETE Transformation of AA to 12-HPETE Transformation of AA to 15-HPETE Transformation of 5-HPETE to 5-HETE Transformation of 12-HPETE to 12-HETE Transformation of 15-HPETE to 15-HETE Transformation of 5-HETE to 5-OXO-ETE Transformation of 5-HPETE to LTA4 Transformation of LTA4 to LTB4 Transformation of LTA4 to LTC4 Transporters Prostaglandin Transporters ATP-Binding Cassette Transporters

Species

Acronym	Name	Species Type
12-LOX	12-Lipoxygenase	Enzyme
15-D-PGJ2	15-Deoxy-Cyclopentenone Prostaglandin	Chemical
15-LOX	15-Lipoxygenase	Enzyme
5-LOX	5-Lipoxygenase	Enzyme
6-K-PGF2α	6-Keto-Prostaglandin F2α	Chemical
AA	Arachidonic Acid	Chemical
COX-1	Cycloxygenase-1	Enzyme
COX-2	Cycloxygenase-2	Enzyme
PL	Phospholipid	Chemical
PGD2	Prostaglandin D2	Chemical
PGDS	Prostaglandin D Synthase	Enzyme
PGE2	Prostaglandin E2	Chemical
PGES	Prostaglandin E Synthase	Enzyme
PGF2α	Prostaglandin F2α	Chemical
PGFS	Prostaglandin F Synthase	Enzyme
PGH2	Prostaglandin H2	Chemical
PGI2	Prostaglandin I2	Chemical
PGJ2	Cyclopentenone Prostaglandin J2	Chemical
PLA2	Phospholipase A2	Enzyme
TXA2	Thromboxane A2	Chemical
TXB2	Thromboxane B2	Chemical
TXAS	Thromboxane A Synthase	Enzyme

Information on the initial concentrations of all species can be found here.

Model Parametrisation

• Enzyme Parameters