Transformation of 5-HPETE to LTA4

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The leukotriene products of the 5-LOX pathway, are important in the inflammation process as they are well-known for the recruitment of infiltrating inflammatory species such as neutrophils and leukocytes (Serhan, Jain et al. 2003, Sadik, Sezin et al. 2013).

The 5-LOX enzyme requires the FLAP protein to be active in the cell, to produce 5-HETE and LTA4.

Reaction

Chemical equation

$5-HPETE \rightleftharpoons LTA4$

Rate equation

Parameters

Note that the literature values are the same as reaction 11.

K_ms

Literature values

Value	Units	Species	Notes	Weight	Reference
5.10E-03	$mM$	Human	Expression Vector: Baculovirus, Sf9 insect cells Enzyme: Recombinant 5-Lipoxygenase pH: 5.6 Temperature:37	256
1.20E-02	$mM$	Human	Expression Vector: Polymorphonuclear Leukocytes Enzyme: 5-Lipoxygenase pH:7.5 Temperature: 22	512
6.31E-02	$mM$	Human	Expression Vector: Polymorphonuclear Leukocytes Enzyme: 5-Lipoxygenase pH:7.5 Temperature: 22	512

Description of the 5-LOX/FLAP Kms distribution

Mode (mM)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
1.27E-02	2.74E+00	-3.76E+00	7.73E-01

The estimated probability distribution for 5-LOX/FLAP 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 5-LOX/FLAP Kmp distribution

Mode (mM)	Location parameter (µ)	Scale parameter (σ)
1.25E-02	-3.63E+00	8.68E-01

The estimated probability distribution for 5-LOX/FLAP 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
1500 + 75	per minute	Potato	Expression Vector:Potato Tubers Enzyme: 5-Lipoxygenase pH:5.5 Temperature: 23	16

Description of the 5-LOX/FLAP kcat distribution

Mode (min-1)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
1.50E+03	1.05E+00	7.31E+00	4.99E-02

The estimated probability distribution for 5-LOX/FLAP 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

Literature values

Value	Units	Species	Notes	Weight	Reference
97.3	$ppm$	Human	Expression Vector: Lung Enzyme: 5-LOX pH: 7.5 Temperature: 37 °C	1024
49.8	$ppm$	Human	Expression Vector: Esophagus Enzyme: 5-LOX pH: 7.5 Temperature: 37 °C	1024
31.9	$ppm$	Human	Expression Vector: Oral Cavity Enzyme: 5-LOX pH: 7.5 Temperature: 37 °C	1024

Description of the 5-LOX concentration distribution

Mode (mM)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
4.96E+01	1.60E+00	4.09E+00	4.28E-01

The estimated probability distribution for 5-LOX/FLAP 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
(-86.007)	kcal/mol	Not stated	Estimated Enzyme: 5-LOX Substrate: 5-HPETE Product: LTA4 pH: 7.3 ionic strength: 0.25	64

Description of the 5-LOX/FLAP Keq distribution

Mode	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
1.31E+63	1.00E+01	1.46E+02	8.90E-01

The estimated probability distribution for 5-LOX/FLAP 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.