Transformation of LTA4 to LTB4

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LTA4 is subsequently enzymatically hydrolysed to LTB4 by LTA4 hydrolase (LTA4H). The enzyme performs this reaction by opening the epoxide and creating a carbocation intermediate. The charge of the carbocation delocalises over the triene system and is subsequently subject to nucleophilic attack by water at C12, resulting in the stereospecific addition of a hydroxyl group and the generation of LTB4.

Reaction

Chemical equation

$LTA4 \rightleftharpoons LTB4$

Rate equation

Parameters

K_ms

Literature values

Value	Units	Species	Notes	Weight	Reference
5.80E-03	mM	Human	Expression Vector: E. Coli Enzyme: Wild Type Leukotriene A4 hydrolase: pH:8 Temperature: 20 (Room Temperature)	128
2.70E-03	mM	Frog	Expression Vector: oocytes Enzyme: leukotriene A4 hydrolase pH:8 Temperature: 20 (Room Temperature)	16
2.20E-02	mM	Human	Expression Vector: Leukocytes Enzyme: Leukotriene A4 Hydrolase pH: 8 Temperature:2°C	256
2.30E-03			Expression Vector: Leukocytes Enzyme: Leukotriene A4 Hydrolase pH: 8 Temperature:37°C	1024

Description of the LTA4H Kms distribution

Mode (mM)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
2.40E-03	5.77E+00	-5.51E+00	7.20E-01

The estimated probability distribution for LTA4H 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 LTA4H Kmp distribution

Mode (mM)	Location parameter (µ)	Scale parameter (σ)
2.40E-03	-5.51E+00	7.17E-01

The estimated probability distribution for LTA4H 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
12.6 - 28.2	per minute	Human	Expression Vector: E. Coli. Enzyme: Leukotriene A4 Hydrolase pH: 7.4 Temperature: 37 °C	1024
51	per minute	Human	Expression Vector: E. Coli Enzyme: Wild Type Leukotriene A4 hydrolase: pH:8 Temperature: 20 (Room Temperature)	128
90	per minute	Frog	Expression Vector: oocytes Enzyme: leukotriene A4 hydrolase pH:8 Temperature: 20 (Room Temperature)	16
125	per minute	Human	Expression Vector: Leukocytes Enzyme: Leukotriene A4 Hydrolase pH: 8 Temperature:37°C	1024

Description of the LTA4H kcat distribution

Mode (min-1)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
2.85E+01	6.56E+00	3.94E+00	7.60E-01

The estimated probability distribution for LTA4H 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
714	$ppm$	Human	Expression Vector: Lung Enzyme: LTA4H pH: 7.5 Temperature: 37 °C	1024
489	$ppm$	Human	Expression Vector: Skin Enzyme: LTA4H pH: 7.5 Temperature: 37 °C	2048
410	$ppm$	Human	Expression Vector: Oral Cavity Enzyme: LTA4H pH: 7.5 Temperature: 37 °C	1024

Description of the LTA4H concentration distribution

Mode (ppm)	Mode (mM)	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
4.88E+02	2.70E-03	1.25E+00	6.24E+00	2.19E-01

The estimated probability distribution for LTA4H 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
(-3.6329994)	kcal/mol	Not stated	Estimated Enzyme: LTA4H Substrate: LTA4 Product: LTB4 pH: 7.3 ionic strength: 0.25	64

Description of the LTA4H Keq distribution

Mode	Confidence Interval	Location parameter (µ)	Scale parameter (σ)
4.64E+02	1.00E+01	6.93E+00	8.90E-01

The estimated probability distribution for LTA4H 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.