Transformation of LTA4 to LTC4

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Leukotriene C4 synthase (LTC4S) transforms LTA4 into LTC4. This reaction involves the conjugation of the LTA4 epoxide and glutathione.

Reaction

R16reaction.png

Chemical equation

 LTA4 \rightleftharpoons LTC4

Rate equation

R16.PNG

Parameters

Kms

Literature Values
Value Units Species Notes Weight Reference
0.3 �± 0.06 mM Human Expression Vector: E. Coli.

Enzyme: Wild Type hLTC4S pH:7.8 Temperature:20 °C

256 [1]
3.00E-02 ± 1.00E-02 mM Human Expression Vector: E Coli

Enzyme: Wild type LTC4S pH: 7.8 Temperature: 37 °C

1024 [2]
Description of the LTC4S Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
3.15E-02 7.18E+00 -2.83E+00 7.90E-01
The estimated probability distribution for LTC4S 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 LTC4S Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
3.18E-02 -2.82E+00 7.92E-01
The estimated probability distribution for LTC4S 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
702 per minute Human Expression Vector: E. Coli.

Enzyme: Wild Type hLTC4S pH:7.8 Temperature:20 °C

256 [1]
1560 ± 240 per minute Human Expression Vector: E Coli

Enzyme: Wild type LTC4S pH: 7.8 Temperature: 37 °C

1024 [2]
Description of the LTC4S kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.47E+03 1.42E+00 7.40E+00 3.29E-01
The estimated probability distribution for LTC4S 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
26.8  ppm Human Expression Vector: Lung

Enzyme: LTC4S pH: 7.5 Temperature: 37 °C

1024 [3]
33.0  ppm Human Expression Vector: Esophagus

Enzyme: LTC4S pH: 7.5 Temperature: 37 °C

2048 [3]
13.9  ppm Human Expression Vector: Adrenal Gland

Enzyme: LTC4S pH: 7.5 Temperature: 37 °C

1024 [3]


Description of the LTC4S concentration distribution
Mode (mM) Mode (ppm) Confidence Interval Location parameter (µ) Scale parameter (σ)
2.90E+01 1.60E-04 1.44E+00 3.49E+00 3.46E-01
The estimated probability distribution for LTC4S 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
9.934128 kcal/mol Not stated Estimated

Enzyme: LTC4S Substrate: LTA4 Product: LTC4 pH: 7.3 ionic strength: 0.25

64 [4]
Description of the LTC4S Keq distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
5.13E-08 1.00E+01 -1.60E+01 8.90E-01
The estimated probability distribution for LTC4S 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.

Related Reactions

References

  1. 1.0 1.1 [http://www.jbc.org/content/285/52/40771.full.pdf Rinaldo A. " Arginine 104 Is a Key Catalytic Residue in Leukotriene C4 Synthase J Biochem 2010, 285, 40771-40776]
  2. 2.0 2.1 [http://www.jbc.org/content/early/2013/12/23/jbc.M113.534628 Niegowski D. " Crystal structures of Leukotriene C4 synthase in complex with product analogs, implications for the enzyme mechanism J. Biol. Chem. 289, 5199-5207 (2014)] Cite error: Invalid <ref> tag; name "Niegowski2013" defined multiple times with different content
  3. 3.0 3.1 3.2 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  4. Caspi et al 2014, "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases," Nucleic Acids Research 42:D459-D471