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

Chemical equation

$AA \rightleftharpoons 15-HPETE$

Rate equation

15-LOX Parameters

K_ms

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
5.00E-03	$mM$	Human	Expression Vector: Reticulocyte Enzyme: 15-Lipoxygenase pH:7.5 Temperature: Unspecified	512
1.06E-02	$mM$	Human	Expression Vector: Keratinocyte Enzyme: 15-Lipoxygenase pH: 6.7 - 7.3 Temperature: 37	2048
1.17E-02 ± 9.00E-04	$mM$	Human	Expression Vector: Baculovirus Insect Cell Enzyme: Wildtype 15-Lipoxygenase pH: 6.8 Temperature: 37	512

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.

K_mp

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.

k_cat

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
37.2 ± 1.8	per minute	Expression Vector:Human prostate epithelial Enzyme:15-lipoxygenase-2	pH 7, Temperature: 22	512
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
37.4	$ppm$	Human	Expression Vector: Spleen Enzyme: 15-LOX pH: 7.5 Temperature: 37 °C	1024
1.40	$ppm$	Human	Expression Vector: Gut Enzyme: 12-LOX pH: 7.5 Temperature: 37 °C	1024

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.

K_eq

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

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.