Transformation of LTA4 to LTC4

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To generate LTC4, a supramolecular complex of 5-LOX, FLAP and leukotriene C4 synthase is formed on the nuclear membrane due to the increase of intracellular calcium \cite{Woods1993, Hammarberg2000, Radmark2015, Evans2008, Mandal2004, Mandal2008}

Reaction

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