Difference between revisions of "Transformation of 5-HPETE to LTA4"

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The 5-LOX enzyme requires the FLAP protein to be active in the cell, to produce 5-HETE and  LTA4.  
 
The 5-LOX enzyme requires the FLAP protein to be active in the cell, to produce 5-HETE and  LTA4.  
−
 
  
 
== Reaction ==
 
== Reaction ==
Line 19: Line 18:
  
 
== Parameters ==
 
== Parameters ==
 +
Note that the literature values are the same as [[Transformation of AA to 5-HPETE|reaction 11]].
  
−
* [[Transformation of AA to 5-HPETE |See 5-LOX enzyme parameters here.]]
+
=== K<sub>ms</sub> ===
  
 
{|class="wikitable sortable"  
 
{|class="wikitable sortable"  
−
|+  style="text-align: left;" | Gibbs Free Energy Change
+
|+  style="text-align: left;" | Literature values
 
|-
 
|-
 
! Value
 
! Value
 +
! Units
 +
! Species
 +
! Notes
 +
! Reference
 +
|-
 +
|5.10E-03
 +
|<math> mM </math>
 +
|Human
 +
|Expression Vector:  Baculovirus, Sf9 insect cells
 +
Enzyme: Recombinant 5-Lipoxygenase
 +
pH: 5.6
 +
Temperature:37
 +
|<ref name="Shirumalla2006”>[http://www.ncbi.nlm.nih.gov/pubmed/17039282 Shirumalla R. K. “RBx 7,796: A novel inhibitor of 5-lipoxygenase.” Inflamm Res. 2006 Dec ; 55 (12) : 517-27.]</ref> 
 +
|-
 +
|1.20E-02
 +
|<math> mM </math>
 +
|Human
 +
|Expression Vector: Polymorphonuclear Leukocytes
 +
Enzyme: 5-Lipoxygenase
 +
pH:7.5
 +
Temperature: 22
 +
|<ref name="Soberman1988"> [http://www.ncbi.nlm.nih.gov/pubmed/3070300 Soberman R. J. "5- and 15(omega-6)-lipoxygenases from human polymorphonuclear leukocytes.'' Methods Enzymol. 1988; 163:344-9.]</ref>
 +
|-
 +
|6.31E-02
 +
|<math> mM </math>
 +
|Human
 +
|Expression Vector: Polymorphonuclear Leukocytes
 +
Enzyme: 5-Lipoxygenase
 +
pH:7.5
 +
Temperature: 22
 +
|<ref name="Soberman1985”>[http://www.ncbi.nlm.nih.gov/pubmed/3920219 Soberman R. J. “Characterization and separation of the arachidonic acid 5-lipoxygenase and linoleic acid omega-6 lipoxygenase (arachidonic acid 15-lipoxygenase) of human polymorphonuclear leukocytes.” J Biol Chem. 1985 Apr 10;260(7):4508-15.]</ref> 
 +
|-
 +
|}
 +
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | 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
 +
|}
 +
 +
[[Image:41.jpg|none|thumb|500px|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<sub>mp</sub>===
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | 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
 +
|}
 +
 +
[[Image:42.jpg|none|thumb|500px|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<sub>cat</sub> ===
 +
{|class="wikitable sortable"
 +
|+  style="text-align: left;" | Literature values
 +
|-
 +
! Value
 +
! Units
 +
! Species
 +
! Notes
 +
! Reference
 +
|-
 +
|1500 + 75
 +
|per minute
 +
|Potato
 +
|Expression Vector:Potato Tubers
 +
Enzyme: 5-Lipoxygenase
 +
pH:5.5
 +
Temperature: 23
 +
|<ref name="Mulliez1987”>[http://www.sciencedirect.com/science/article/pii/0167483887902056 Mulliez E., “5-Lipoxygenase from potato tubers. Improved purification and physicochemical characteristics” Biochimica et Biophysica Acta, 1987;916(1):13-23.]</ref> 
 +
|-
 +
 +
|}
 +
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | 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
 +
|}
 +
 +
[[Image:43.jpg|none|thumb|500px|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 ===
 +
{|class="wikitable sortable"
 +
|+  style="text-align: left;" | Literature values
 +
|-
 +
! Value
 +
! Units
 +
! Species
 +
! Notes
 +
! Reference
 +
|-
 +
|97.3
 +
|<math> ppm </math>
 +
|Human
 +
|Expression Vector: Lung
 +
Enzyme: 5-LOX
 +
pH: 7.5
 +
Temperature: 37 °C
 +
|<ref name="Kim2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13302.pdf M. Kim ''A draft map of the human proteome'' Nature, 2014 509, 575–581]</ref>
 +
|-
 +
|49.8
 +
|<math> ppm </math>
 +
|Human
 +
|Expression Vector: Esophagus
 +
Enzyme: 5-LOX
 +
pH: 7.5
 +
Temperature: 37 °C
 +
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the human proteome'' Nature, 2014 509, 582–587]</ref>
 +
|-
 +
|31.9
 +
|<math> ppm </math>
 +
|Human
 +
|Expression Vector: Oral Cavity
 +
Enzyme: 5-LOX
 +
pH: 7.5
 +
Temperature: 37 °C
 +
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the human proteome'' Nature, 2014 509, 582–587]</ref>
 +
|-
 +
|}
 +
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | 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
 +
|}
 +
 +
[[Image:158.jpg|none|thumb|500px|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<sub>eq</sub> ===
 +
{|class="wikitable sortable"
 +
|+  style="text-align: left;" | Literature values
 +
|-
 +
! Gibbs Free Energy Change
 
! Units
 
! Units
 
! Species
 
! Species
Line 42: Line 182:
 
|<ref name="MetaCyc”>[http://metacyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-13395 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]</ref>
 
|<ref name="MetaCyc”>[http://metacyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-13395 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]</ref>
 
|}
 
|}
 +
 +
[[Image:44.jpg|none|thumb|500px|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.  ]]
  
 
== References ==
 
== References ==
 
<references/>
 
<references/>
 
== Related Reactions ==
 
== Related Reactions ==

Revision as of 10:52, 15 May 2019

Return to overview

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

R13 HPETE5-LTA4.jpg

Chemical equation

5-HPETE \rightleftharpoons LTA4

Rate equation

R13.PNG

Parameters

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

Kms

Literature values
Value Units Species Notes Reference
5.10E-03 mM Human Expression Vector: Baculovirus, Sf9 insect cells

Enzyme: Recombinant 5-Lipoxygenase pH: 5.6 Temperature:37

[1]
1.20E-02 mM Human Expression Vector: Polymorphonuclear Leukocytes

Enzyme: 5-Lipoxygenase pH:7.5 Temperature: 22

[2]
6.31E-02 mM Human Expression Vector: Polymorphonuclear Leukocytes

Enzyme: 5-Lipoxygenase pH:7.5 Temperature: 22

[3]
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.

Kmp

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.


kcat

Literature values
Value Units Species Notes Reference
1500 + 75 per minute Potato Expression Vector:Potato Tubers

Enzyme: 5-Lipoxygenase pH:5.5 Temperature: 23

[4]
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 Reference
97.3 ppm Human Expression Vector: Lung

Enzyme: 5-LOX pH: 7.5 Temperature: 37 °C

[5]
49.8 ppm Human Expression Vector: Esophagus

Enzyme: 5-LOX pH: 7.5 Temperature: 37 °C

[6]
31.9 ppm Human Expression Vector: Oral Cavity

Enzyme: 5-LOX pH: 7.5 Temperature: 37 °C

[6]
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.


Keq

Literature values
Gibbs Free Energy Change Units Species Notes Reference
(-86.007) kcal/mol Not stated Estimated

Enzyme: 5-LOX Substrate: 5-HPETE Product: LTA4 pH: 7.3 ionic strength: 0.25

[7]
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.

References

  1. ↑ Shirumalla R. K. “RBx 7,796: A novel inhibitor of 5-lipoxygenase.” Inflamm Res. 2006 Dec ; 55 (12) : 517-27.
  2. ↑ Soberman R. J. "5- and 15(omega-6)-lipoxygenases from human polymorphonuclear leukocytes. Methods Enzymol. 1988; 163:344-9.
  3. ↑ Soberman R. J. “Characterization and separation of the arachidonic acid 5-lipoxygenase and linoleic acid omega-6 lipoxygenase (arachidonic acid 15-lipoxygenase) of human polymorphonuclear leukocytes.” J Biol Chem. 1985 Apr 10;260(7):4508-15.
  4. ↑ Mulliez E., “5-Lipoxygenase from potato tubers. Improved purification and physicochemical characteristics” Biochimica et Biophysica Acta, 1987;916(1):13-23.
  5. ↑ M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  6. ↑ 6.0 6.1 M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  7. ↑ 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

Related Reactions

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