View source for Transformation of AA to PGH2 (COX-1)

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The COX enzyme possesses two isoforms, COX-1 and COX-2, of which both produce bioactive eicosanoids. The two isoforms have nearly identical active site residues (Simmons et al. 2004), but COX-1 is a constitutive enzyme, whereas COX-2 is an inducible enzyme. Both enzymes add molecular oxygen to arachidonic acid, generating an endoperoxide species, PGH2, by catalysing the two-step reaction of cycloooxygenation and oxygenation, followed by a hydroperoxide reduction. 

PGH2 possesses a short life time due to the formation of a reactive functional group. The endoperoxide undergoes rapid isomerisation reactions, catalysed by a series of synthase enzymes (PGES, PGDS, PGIS, PGFS and TXAS). The resultant species of the isomerisation reactions are PGs (PGE2, PGD2, PGJ2, deoxy-PGJ2 and PGF2α), TXs (TXA2 and TXB2) and prostacyclin (PGI2), all of which have varying effects on the immune system.

== Reaction ==

[[File:R2_AA-PGH2.jpg|center|500px]]

==Chemical equation==

<center><math> AA \rightleftharpoons PGH2 </math></center>

== Rate equation ==
[[File:R65.PNG|center|500px]]

== Enzyme Parameters ==

=== K<sub>eq</sub> ===
{|class="wikitable sortable" 
|+  style="text-align: left;" | Gibbs Free Energy Change
|-
! Value
! Units
! Species
! Notes
! Reference
|-
|(-30)
|kcal/mol
|Unspecified
|Calculations with a Gaussian98 suite of programs
Enzyme: COX (Unspecific)
Substrate: Arachidonate
Temperature: 298.15 K
Pressure: 1 bar
|<ref name="Silva2003”>[http://link.springer.com/article/10.1007/s00214-003-0476-9 P. Silva, "A theoretical study of radical-only and combined radical/carbocationic mechanisms of arachidonic acid cyclooxygenation by prostaglandin H synthase" Theor Chem Acc (2003) 110: 345]</ref>
|-
|}

{| class="wikitable"
|+  style="text-align: left;" | Description of the COX-1 Keq distribution
! Mode !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
|-
| 4.18E+28 || 1.00E+01 || 6.67E+01 || 8.90E-01
|-
|}

[[Image:72.jpg|none|thumb|500px|The estimated probability distribution for COX-1 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.   ]]

=== K<sub>ms</sub> ===
{|class="wikitable sortable" 
|+  style="text-align: left;" | COX-1 Michaelis-Menten Constants
|-
! Value
! Units
! Species
! Notes
! Reference
|-
|0.0088 ± 0.0022
|<math> mM </math>
|Human 
|Expression Vector: Human
Enzyme: Cyclooxygenase-1
pH: 7.6 - 8.4
Temperature: 37 °C
|<ref name="Noreen1998"> [http://pubs.acs.org/doi/abs/10.1021/np970343j Y. ''Noreen Development of a Radiochemical Cyclooxygenase-1 and -2 in Vitro Assay for Identification of Natural Products as Inhibitors of Prostaglandin Biosynthesis''J. Nat. Prod., 1998, 61 (1), pp 2–7)]</ref>
|-
|0.0019 ± 0.0002
|<math> mM </math>
|Ram
|Expression Vector: Ram
Enzyme: Cyclooxygenase-1
pH: 8
Temperature: 30 ± 0.2 °C
|<ref name="Mukherjee2007"> [http://pubs.acs.org/doi/abs/10.1021/bi602502jA. Mukherjee ''Molecular Oxygen Dependent Steps in Fatty Acid Oxidation by Cyclooxygenase-1'' Biochemistry, 2007, 46 (13), pp 3975–3989]</ref>
|}

{| class="wikitable"
! Mode !! Confidence Interval  !! Location parameter (µ) !! Scale parameter (σ)
|-
| 8.30E-03 || 1.62E+00 || -4.60E+00 || 4.41E-01
|}

[[Image:69.jpg|none|thumb|500px|The estimated probability distribution for COX-2 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<sub>mp</sub> ===
{| class="wikitable"
! Mode (mM) !! Location parameter (μ) !! Scale parameter (σ)
|-
| 8.20E-03 || -4.60E+00 || 4.49E-01
|}

[[Image:70.jpg|none|thumb|500px|The estimated probability distribution for COX-2 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<sub>cat</sub> ===
{|class="wikitable sortable" 
|+  style="text-align: left;" | COX-1 Turnover Number
|-
! Value
! Units
! Species
! Notes
! Reference
|-
|8820 ± 360
|<math> per minute </math>
|Ram
|Expression Vector: Ram
Enzyme: Cyclooxygenase-1
pH: 8
Temperature: 30 ± 0.2 °C
|<ref name="Mukherjee2007"> [http://pubs.acs.org/doi/abs/10.1021/bi602502jA. Mukherjee ''Molecular Oxygen Dependent Steps in Fatty Acid Oxidation by Cyclooxygenase-1'' Biochemistry, 2007, 46 (13), pp 3975–3989]</ref>
|-

|}

{| class="wikitable"
! Mode (min-1) !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
|-
| 8.81E+03 || 1.04E+00 || 9.09E+00 || 4.08E-02
|}

[[Image:71.jpg|none|thumb|500px|The estimated probability distribution for COX-1 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.   ]]

=== Enzyme concentration ===

{|class="wikitable sortable" 
|+  style="text-align: left;" | COX-1 Abundance
|-
! Value
! Units
! Species
! Notes
! Reference
|-
|1176
|<math> ppm </math>
|Human 
|Expression Vector: Urinary Bladder
Enzyme: Cyclooxygenase-1 (PGTS1)
pH: 7.5
Temperature: 37 °C
|<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref>
|-
|849
|<math> ppm </math>
|Human 
|Expression Vector: Platlet
Enzyme: Cyclooxygenase-1 (PGTS1)
pH: 7.5
Temperature: 37 °C
|<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref>
|-
|208
|<math> ppm </math>
|Human 
|Expression Vector: Stomach
Enzyme: Cyclooxygenase-1 (PGTS1)
pH: 7.5
Temperature: 37 °C
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
human proteome'' Nature, 2014 509, 582–587]</ref>
|-
|130
|<math> ppm </math>
|Human 
|Expression Vector: Esophagus
Enzyme: Cyclooxygenase-1 (PGTS1)
pH: 7.5
Temperature: 37 °C
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
human proteome'' Nature, 2014 509, 582–587]</ref>
|-
|70.8
|<math> ppm </math>
|Human 
|Expression Vector: Oral Cavity
Enzyme: Cyclooxygenase-1 (PGTS1)
pH: 7.5
Temperature: 37 °C
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
human proteome'' Nature, 2014 509, 582–587]</ref>
|-
|19.1
|<math> ppm </math>
|Human 
|Expression Vector: Lung
Enzyme: Cyclooxygenase-1 (PGTS1)
pH: 7.5
Temperature: 37 °C
|<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref>
|-
|}

{| class="wikitable"
! Mode (mM) !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
|-
| 4.18E+28 || 1.00E+01 || 6.67E+01 || 8.90E-01
|}

[[Image:154.jpg|none|thumb|500px|The estimated probability distribution for COX-1 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.   ]]

== References ==
<references/>

== Related Reactions ==
* [[Transformation of PL to AA |Transformation of PL to AA]] 
* [[Transformation of PGH2 to PGF2α |Transformation of PGH2 to PGF2α]]
* [[Transformation of PGH2 to TXA2  |Transformation of PGH2 to TXA2]]
* [[Transformation of PGH2 to PGI2 |Transformation of PGH2 to PGI2]]
* [[Transformation of PGH2 to PGD2 |Transformation of PGH2 to PGD2]]
* [[Transformation of PGH2 to PGE2 |Transformation of PGH2 to PGE2]]