Transformation of AA to 15-HPETE

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The genes ALOX15B and ALOX15 encodes the formation of two isoforms of 15-lioxygenase (15-LOX). The gene ALOX15B encodes the formation of 15-LOX-2, which converts AA exclusively into 15(S)-HPETE. Whereas the gene ALOX15 encodes the 15-LOX-1 protein, which converts AA into both 12(S)-HPETE and 15(S)-HPETE. The formation of the unstable hydroperoxy fatty acids (HPETE) begins with the abstraction of a hydrogen radical at the allylic position between two double bonds. The structure undergoes a rearrangement reaction which results in the formation of a conjugated diene system. The insertion of molecular oxygen and a hydrogen leads to the formation of the final structure, a hydroperoxy fatty acid.

Reaction

R17 AA - HPETE15.jpg

Chemical equation

 AA \rightleftharpoons 15-HPETE

Rate equation

R17.PNG

15-LOX Parameters

Kms

Literature values
Value Units Species Notes Weight Reference
3.70E-03 ± 3.00E-04  mM Human Expression Vector: Epithelium

Enzyme: 15-Lipoxygenase pH: 7.5 Temperature: 25

512 [1]
5.00E-03  mM Human Expression Vector: Reticulocyte

Enzyme: 15-Lipoxygenase pH:7.5 Temperature: Unspecified

512 [2]
1.06E-02  mM Human Expression Vector: Keratinocyte

Enzyme: 15-Lipoxygenase pH: 6.7 - 7.3 Temperature: 37

2048 [3]
1.17E-02 ± 9.00E-04  mM Human Expression Vector: Baculovirus Insect Cell

Enzyme: Wildtype 15-Lipoxygenase pH: 6.8 Temperature: 37

512 [4]
Description of the 15-LOX Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.02E-02 2.40E+00 -4.42E+00 4.10E-01
The estimated probability distribution for 15-LOX 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

Description of the 15-LOX Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
1.02E-02 -4.42E+00 4.11E-01
The estimated probability distribution for 15-LOX 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
595.8 ± 16.8  minute^{-1} Human Expression Vector: Epithelium

Enzyme: 15-Lipoxygenase pH: 7.5 Temperature: 25

512 [1]
37.2 ± 1.8 per minute Expression Vector:Human prostate epithelial

Enzyme:15-lipoxygenase-2

pH 7, Temperature: 22 512 [5]
45 ± 1.2 pH 7.5, Temperature: 22
44.4 ± 2.4 pH 8, Temperature: 22
34.2 ± 0.6 15°C, pH = 7.5
45 ± 1.2 22°C, pH = 7.5
62.4 ± 4.2 30°C, pH = 7.5
82.8 ± 4.8 37°C, pH = 7.5
Description of the 15-LOX kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
6.51E+01 4.62E+00 4.60E+00 6.50E-01
The estimated probability distribution for 15-LOX kcat. 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

To convert the enzyme concentration from ppm to mM, the following equation was used.

Literature values
Value Units Species Notes Weight Reference
4.09  ppm Human Expression Vector: Lung

Enzyme: 15-LOX pH: 7.5 Temperature: 37 °C

1024 [6]
37.4  ppm Human Expression Vector: Spleen

Enzyme: 15-LOX pH: 7.5 Temperature: 37 °C

1024 [7]
1.40  ppm Human Expression Vector: Gut

Enzyme: 12-LOX pH: 7.5 Temperature: 37 °C

1024 [6]
Description of the 15-LOX concentration distribution
Mode (ppm) Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
4.07 2.25E-05 7.23E+00 7.12E-01 1.19E+00
The estimated probability distribution for 15-LOX 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.

Keq

Literature values
Gibbs Free Energy Change Units Species Notes Weight Reference
(-69.979996) kcal/mol Not stated Estimated

Enzyme: 15-LOX Substrate: Arachidonate Product: 15-HPETE pH: 7.3 ionic strength: 0.25

64 [8]
Description of the 15-LOX Keq distribution
Mode Confidence Interval Location parameter (µ) Scale parameter (σ)
2.27E+51 1.00E+01 1.19E+02 8.90E-01
The estimated probability distribution for 15-LOX 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.

References

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