Difference between revisions of "Transformation of AA to PGH2 (COX-1)"

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|+  style="text-align: left;" | Description of the COX-1 concentration distribution
 
|+  style="text-align: left;" | Description of the COX-1 concentration distribution
! Mode (mM) !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
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! Mode (ppm) !! Mode (mM) !! Confidence Interval  !! Location parameter (μ) !! Scale parameter (σ)
 
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| 4.18E+28 || 1.00E+01 || 6.67E+01 || 8.90E-01
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| 4.18E+28 || 7.14E-04 || 1.00E+01 || 6.67E+01 || 8.90E-01
 
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Revision as of 08:23, 30 May 2019

Return to overview

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

R2 AA-PGH2.jpg

Chemical equation

 AA \rightleftharpoons PGH2

Rate equation

R65.PNG

Enzyme Parameters

Keq

Literature values
Value Units Species Notes Weight Reference
(-30) kcal/mol Unspecified Calculations with a Gaussian98 suite of programs

Enzyme: COX (Unspecific) Substrate: Arachidonate Temperature: 298.15 K Pressure: 1 bar

64 [1]
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
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.

Kms

Literature values
Value Units Species Notes Weight Reference
0.0088 ± 0.0022  mM Human Expression Vector: Human

Enzyme: Cyclooxygenase-1 pH: 7.6 - 8.4 Temperature: 37 °C

2048 [2]
0.0019 ± 0.0002  mM Ram Expression Vector: Ram

Enzyme: Cyclooxygenase-1 pH: 8 Temperature: 30 ± 0.2 °C

192 [3]
Description of the COX-1 Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
8.30E-03 1.62E+00 -4.60E+00 4.41E-01
The estimated probability distribution for COX-1 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.

Kmp

This is a “Dependent parameter”, meaning that the log-normal distribution for this parameter was calculated using multivariate distributions (this is discussed in detail here). As a result, no confidence interval factor or literature values were cited for this parameter.

Description of the COX-1 Kmp distribution
Mode (mM) Location parameter (μ) Scale parameter (σ)
8.20E-03 -4.60E+00 4.49E-01
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.

kcat

Literature values
Value Units Species Notes Weight Reference
8820 ± 360  per minute Ram Expression Vector: Ram

Enzyme: Cyclooxygenase-1 pH: 8 Temperature: 30 ± 0.2 °C

192 [3]
Description of the COX-1 kcat distribution
Mode (min-1) Confidence Interval Location parameter (μ) Scale parameter (σ)
8.81E+03 1.04E+00 9.09E+00 4.08E-02
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

Literature values
Value Units Species Notes Weight Reference
849  ppm Human Expression Vector: Platlet

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [4]
208  ppm Human Expression Vector: Stomach

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [5]
130  ppm Human Expression Vector: Esophagus

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [5]
70.8  ppm Human Expression Vector: Oral Cavity

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [5]
19.1  ppm Human Expression Vector: Lung

Enzyme: Cyclooxygenase-1 (PGTS1) pH: 7.5 Temperature: 37 °C

1024 [4]
Description of the COX-1 concentration distribution
Mode (ppm) Mode (mM) Confidence Interval Location parameter (μ) Scale parameter (σ)
4.18E+28 7.14E-04 1.00E+01 6.67E+01 8.90E-01
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

Related Reactions