Difference between revisions of "Transformation of PGH2 to PGE2"

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[[File:R10.PNG|center|500px]]
 
[[File:R10.PNG|center|500px]]
  
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== PGES Enzyme Parameters ==
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== Parameters ==
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=== K<sub>ms</sub> ===
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
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|+  style="text-align: left;" | Michaelis-Menten Constants
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|+  style="text-align: left;" | Literature values
 
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|-
 
! Value
 
! Value
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|}
 
|}
  
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{| class="wikitable"
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|+  style="text-align: left;" | Description of the PGES Kms distribution
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! Mode (mM) !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ)
 +
|-
 +
| 1.97E-01 || 1.73E+00 || -1.39E+00 || 4.91E-01
 +
|}
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=== K<sub>mp</sub>===
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{| class="wikitable"
 +
|+  style="text-align: left;" | Description of the PGES Kmp distribution
 +
! Mode (mM) !! Location parameter (µ) !! Scale parameter (σ)
 +
|-
 +
| 1.93E-01 || -1.15E+00 || 7.02E-01 (mM)
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|}
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=== k<sub>cat</sub>===
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
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|+  style="text-align: left;" | Enzyme Turnover Numbers
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|+  style="text-align: left;" | Literature values
 
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|-
 
! Value
 
! Value
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|}
 
|}
  
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{| class="wikitable"
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! Mode (min-1) !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ)
 +
|-
 +
| 2.98E+03 || 1.13E+00 || 8.01E+00 || 1.19E-01
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|}
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 +
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=== Enzyme concentration ===
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
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|+  style="text-align: left;" | PGES Abundance
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|+  style="text-align: left;" | Literature values
 
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|-
 
! Value
 
! Value
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|-
 
|-
 
|}
 
|}
 +
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | 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
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|}
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=== K<sub>eq </sub> ===
  
 
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{|class="wikitable sortable"  
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|<ref name="MetaCyc”>[http://metacyc.org/META/NEW-IMAGE?type=REACTION&object=PROSTAGLANDIN-E-SYNTHASE-RXN Caspi et al 2014, "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases," Nucleic Acids Research 42:D459-D471]</ref>
 
|<ref name="MetaCyc”>[http://metacyc.org/META/NEW-IMAGE?type=REACTION&object=PROSTAGLANDIN-E-SYNTHASE-RXN Caspi et al 2014, "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases," Nucleic Acids Research 42:D459-D471]</ref>
 
|}
 
|}
 +
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | 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
 +
|}
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 +
  
 
== References ==
 
== References ==

Revision as of 09:29, 15 May 2019

Return to overview

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

R10 PGH2 - PGE2.jpg

Chemical equation

PGH2 \rightleftharpoons PGE2

Rate equation

R10.PNG

Parameters

Kms

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

[1]
2.15E-01 mM Human Wild Type Enzyme [2]
1.49E-02 mM Human Expression Vector: E. Coli

Enzyme: PGES pH: Unknown Temperature: Unknown

Other: cPGES, casein kinase II and Hsp90

[3]
6.66E-02 mM Human Expression Vector: E. Coli

Enzyme: PGES pH: Unknown Temperature: Unknown

[3]
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

Kmp

Description of the PGES Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
1.93E-01 -1.15E+00 7.02E-01 (mM)


kcat

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

[4]
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
2.98E+03 1.13E+00 8.01E+00 1.19E-01


Enzyme concentration

Literature values
Value Units Species Notes Reference
220 ppm Human Expression Vector: Placenta

Enzyme: PGES pH: 7.5 Temperature: 37 °C

[5]
75.3 ppm Human Expression Vector: Urinary Bladder

Enzyme: PGES pH: 7.5 Temperature: 37 °C

[6]
208 ppm Human Expression Vector: Stomach

Enzyme: PGES pH: 7.5 Temperature: 37 °C

[5]
28.1 ppm Human Expression Vector: Lung

Enzyme: PGES pH: 7.5 Temperature: 37 °C

[6]
11.6 ppm Human Expression Vector: Colon

Enzyme: PGES pH: 7.5 Temperature: 37 °C

[6]
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


Keq

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

[7]
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


References

  1. ↑ Pettersson P. , "Identification of beta-trace as prostaglandin D synthase. FASEB J. 2010 Dec;24(12):4668-77. doi: 10.1096/fj.10-164863. Epub 2010 Jul 28.
  2. ↑ Hamza A. , "Understanding microscopic binding of human microsomal prostaglandin E synthase-1 (mPGES-1) trimer with substrate PGH2 and cofactor GSH: insights from computational alanine scanning and site-directed mutagenesis. J Phys Chem B. 2010 Apr 29;114(16):5605-16. doi: 10.1021/jp100668y.
  3. ↑ 3.0 3.1 Kobayashi T. , "Regulation of cytosolic prostaglandin E synthase by phosphorylation. Biochem J. 2004 Jul 1;381(Pt 1):59-69.
  4. ↑ [www.ncbi.nlm.nih.gov/pubmed/16399384 Pettersson P., "Human microsomal prostaglandin E synthase 1: a member of the MAPEG protein superfamily. Methods Enzymol. 2005;401:147-61.]
  5. ↑ 5.0 5.1 M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  6. ↑ 6.0 6.1 6.2 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  7. ↑ Caspi et al 2014, "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases," Nucleic Acids Research 42:D459-D471


Related Reactions

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