Difference between revisions of "Transformation of AA to PGH2 (COX-1)"
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== Enzyme Parameters == | == Enzyme Parameters == | ||
− | === K<sub>eq<\sub> | + | === K<sub>eq<\sub> === |
{|class="wikitable sortable" | {|class="wikitable sortable" | ||
|+ style="text-align: left;" | Gibbs Free Energy Change | |+ style="text-align: left;" | Gibbs Free Energy Change | ||
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|} | |} | ||
+ | {| 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. ]] | [[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> === | === 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. ]] | [[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. ]] | ||
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|- | |- | ||
+ | |} | ||
+ | |||
+ | {| 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 | ||
|} | |} | ||
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|} | |} | ||
− | + | {| 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. ]] | [[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. ]] |
Revision as of 15:19, 14 May 2019
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.
Contents
Reaction
Chemical equation
Rate equation
Enzyme Parameters
Keq<\sub>
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 |
[1] |
Mode | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
4.18E+28 | 1.00E+01 | 6.67E+01 | 8.90E-01 |
Kms<\sub>
Value | Units | Species | Notes | Reference |
---|---|---|---|---|
0.0088 ± 0.0022 | Human | Expression Vector: Human
Enzyme: Cyclooxygenase-1 pH: 7.6 - 8.4 Temperature: 37 °C |
[2] | |
0.0019 ± 0.0002 | Ram | Expression Vector: Ram
Enzyme: Cyclooxygenase-1 pH: 8 Temperature: 30 ± 0.2 °C |
[3] |
Mode | Confidence Interval | Location parameter (µ) | Scale parameter (σ) |
---|---|---|---|
8.30E-03 | 1.62E+00 | -4.60E+00 | 4.41E-01 |
Kmp<\sub>
Mode (mM) | Location parameter (μ) | Scale parameter (σ) |
---|---|---|
8.20E-03 | -4.60E+00 | 4.49E-01 |
kcat<\sub>
Value | Units | Species | Notes | Reference |
---|---|---|---|---|
8820 ± 360 | Ram | Expression Vector: Ram
Enzyme: Cyclooxygenase-1 pH: 8 Temperature: 30 ± 0.2 °C |
[3] |
Mode (min-1) | Confidence Interval | Location parameter (μ) | Scale parameter (σ) |
---|---|---|---|
8.81E+03 | 1.04E+00 | 9.09E+00 | 4.08E-02 |
Enzyme concentration
Value | Units | Species | Notes | Reference |
---|---|---|---|---|
1176 | Human | Expression Vector: Urinary Bladder
Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C |
[4] | |
849 | Human | Expression Vector: Platlet
Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C |
[4] | |
208 | Human | Expression Vector: Stomach
Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C |
[5] | |
130 | Human | Expression Vector: Esophagus
Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C |
[5] | |
70.8 | Human | Expression Vector: Oral Cavity
Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C |
[5] | |
19.1 | Human | Expression Vector: Lung
Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C |
[4] |
Mode (mM) | Confidence Interval | Location parameter (μ) | Scale parameter (σ) |
---|---|---|---|
4.18E+28 | 1.00E+01 | 6.67E+01 | 8.90E-01 |
References
- ↑ 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
- ↑ Y. Noreen Development of a Radiochemical Cyclooxygenase-1 and -2 in Vitro Assay for Identification of Natural Products as Inhibitors of Prostaglandin BiosynthesisJ. Nat. Prod., 1998, 61 (1), pp 2–7)
- ↑ 3.0 3.1 Mukherjee Molecular Oxygen Dependent Steps in Fatty Acid Oxidation by Cyclooxygenase-1 Biochemistry, 2007, 46 (13), pp 3975–3989
- ↑ 4.0 4.1 4.2 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
- ↑ 5.0 5.1 5.2 [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]
Related Reactions
- Transformation of PL to AA
- 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