Difference between revisions of "Transformation of 5-HETE to 5-OXO-ETE"

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| Unkown
 
| Unkown
 
| Follows a ping-pong mechanism by binding with NADP+, transforming it to NADPH and releasing it before binding 5S-HETE.  
 
| Follows a ping-pong mechanism by binding with NADP+, transforming it to NADPH and releasing it before binding 5S-HETE.  
 +
|64
 
| <ref name="Steinhilber"> [https://books.google.co.uk/books?id=mEYWDAAAQBAJ&pg=PA188&lpg=PA188&dq=5-HEDH+Km&source=bl&ots=dwhpDJqBhn&sig=jgK1WqNLlylOaNedgGdwNBQN7TM&hl=en&sa=X&ved=0ahUKEwiw_pCykbfPAhVDD8AKHZu2BnwQ6AEIHDAA#v=onepage&q=5-HEDH%20Km&f=false Lipoxygenases in Inflammation - edited by Dieter Steinhilber]</ref>  
 
| <ref name="Steinhilber"> [https://books.google.co.uk/books?id=mEYWDAAAQBAJ&pg=PA188&lpg=PA188&dq=5-HEDH+Km&source=bl&ots=dwhpDJqBhn&sig=jgK1WqNLlylOaNedgGdwNBQN7TM&hl=en&sa=X&ved=0ahUKEwiw_pCykbfPAhVDD8AKHZu2BnwQ6AEIHDAA#v=onepage&q=5-HEDH%20Km&f=false Lipoxygenases in Inflammation - edited by Dieter Steinhilber]</ref>  
 
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pH: 7.4
 
pH: 7.4
 
Temperature:  37 ◦C  
 
Temperature:  37 ◦C  
 +
|2048
 
| <ref name="ERLEMANN2007"> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828885/pdf/bj4030157.pdf Karl-Rudolf ERLEMANN, Regulation of 5-hydroxyeicosanoid dehydrogenase activity in
 
| <ref name="ERLEMANN2007"> [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828885/pdf/bj4030157.pdf Karl-Rudolf ERLEMANN, Regulation of 5-hydroxyeicosanoid dehydrogenase activity in
 
monocytic cells, Biochem. J. (2007) 403, 157–165]</ref>  
 
monocytic cells, Biochem. J. (2007) 403, 157–165]</ref>  
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pH: 7.4
 
pH: 7.4
 
Temperature:  37 ◦C  
 
Temperature:  37 ◦C  
 +
|2048
 
| <ref name="Patel2009"> [http://jpet.aspetjournals.org/content/jpet/329/1/335.full.pdf Karl-Pranav Patel, Selectivity of 5-Hydroxyeicosanoid Dehydrogenase
 
| <ref name="Patel2009"> [http://jpet.aspetjournals.org/content/jpet/329/1/335.full.pdf Karl-Pranav Patel, Selectivity of 5-Hydroxyeicosanoid Dehydrogenase
 
and Its Inhibition by 5-Hydroxy-Long-Chain Fatty Acids, Journal of Pharmacology and Experimental Therapeutics April 2009, 329 (1) 335-341; ]</ref>  
 
and Its Inhibition by 5-Hydroxy-Long-Chain Fatty Acids, Journal of Pharmacology and Experimental Therapeutics April 2009, 329 (1) 335-341; ]</ref>  
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Substrate: NADPH
 
Substrate: NADPH
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|128
 
| B
 
| B
 
|}
 
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pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
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|2048
 
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
|<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>
 
human proteome'' Nature, 2014 509, 582–587]</ref>
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pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|1024
 
|<ref name="Wilhelm2014"> [http://www.nature.com/nature/journal/v509/n7502/pdf/nature13319.pdf M. Wilhelm ''Mass-spectrometry-based draft of the
 
|<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>
 
human proteome'' Nature, 2014 509, 582–587]</ref>
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pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
 +
|1024
 
|<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>
 
|<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>
 
|-
 
|-
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pH: Unknown
 
pH: Unknown
 
Temperature: Unknown
 
Temperature: Unknown
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|2048
 
|<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>
 
|<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>
 
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pH: 7.3  
 
pH: 7.3  
 
ionic strength: 0.25
 
ionic strength: 0.25
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|64
 
|<ref name="MetaCyc”>[https://metacyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-16416 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”>[https://metacyc.org/META/NEW-IMAGE?type=REACTION&object=RXN-16416 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>
 
|}
 
|}
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[[Image:48.jpg|none|thumb|500px|The estimated probability distribution for 5-HEDH 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.  ]]
 
[[Image:48.jpg|none|thumb|500px|The estimated probability distribution for 5-HEDH 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 ==
 
== Related Reactions ==

Revision as of 11:25, 22 May 2019

Return to overview

The metabolism of 5-HETE to 5-Oxo-ETE is catalysed by the enzyme 5-Hydroxyeicosanoid dehydrogenase (5-HEDH). This enzyme acts reversibly and has been reported to be found in eosinophils, monocytes, DC, B-lymphocytes, keratinocytes and platelets (Steinhilber book) *skin (need to check). The product binds with the OXE receptor (Hosoi2002) and is 30-100 more bioactive than 5-HETE. 5-Oxo-ETE is a chemoattractant for neutrophils and eosinophils.

Reaction

R14 HETE5-OETE5.jpg

Chemical equation

5-HETE \rightleftharpoons 5-Oxo-ETE

Rate equation

R14.PNG

Parameters

Note that there was limited availability of kinetic data for this specific enzyme, therefore parameters for general alcohol dehydrogenase (ADH) was used when non were available.

Kms

Literature Values
Value Units Species Notes Weight Reference
0.0006 mM Unkown Follows a ping-pong mechanism by binding with NADP+, transforming it to NADPH and releasing it before binding 5S-HETE. 64 [1]
0.00067 mM Human Cell lines Follows a ping-pong mechanism by binding with NADP+ (Km 139 nM), transforming it to NADPH (inhibited by NADPH (Ki 224 nM)) and releasing it before binding 5S-HETE.

Method: In vitro Organism: Human Expression vector: U937 and HL-60 cell lines Enzyme:5-HEDH pH: 7.4 Temperature: 37 ◦C

2048 [2]
0.000516 ± 0.00019 mM Human Cell lines

Method: In vitro Organism: Human Expression vector: U937 Enzyme:5-HEDH pH: 7.4 Temperature: 37 ◦C

2048 [3]
Description of the 5-HEDH Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
6.34E-04 1.63E+01 -6.31E+00 1.03E+00
The estimated probability distribution for 5-HEDH 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

This is a “Dependent parameter”, meaning that the log-normal distribution for this parameter was calculated using multivariate distributions (this is discussed in detail here). As a result, no confidence interval factor or literature values were cited for this parameter.

Description of the 5-HEDH Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
1.14E+04 1.09E+01 1.25E+00
The estimated probability distribution for 5-HEDH 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.


Vmax

Literature values
Value Units Species Notes Reference
0.54 ± 0.30 pmol/ mi mg Human Cell lines - Neutrophils

Method: In vitro Organism: Human Expression vector: U937 and HL-60 cell lines Enzyme:5-HEDH pH: 7.4 Temperature: 37 ◦C

[2]
0.40 ± 0.12 pmol/ mi mg Human Cell lines - U937

Method: In vitro Organism: Human Expression vector: U937 and HL-60 cell lines Enzyme:5-HEDH pH: 7.4 Temperature: 37 ◦C

[2]

kcat

Literature values
Value Units Species Notes Weight Reference
11640 ± 840 min-1 Yokenella Method: In vitro

Organism: Human Expression vector: E Coli Enzyme: pH: 6.5 Temperature: 65 ◦C

Substrate: NADPH

128 B
Description of the 5-HEDH kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.15E+04 4.02E+01 1.09E+01 1.25E+00
The estimated probability distribution for 5-HEDH 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 (Using ADH5 abundance data)

Literature values
Value Units Species Notes Weight Reference
490 ppm Human Expression Vector: Skin

Enzyme: ADH5 pH: 7.5 Temperature: 37 °C

2048 [4]
625 ppm Human Expression Vector: Oral Cavity

Enzyme: ADH5 pH: 7.5 Temperature: 37 °C

1024 [4]
728 ppm Human Expression Vector: Esophagus

Enzyme: ADH5 pH: 7.5 Temperature: 37 °C

1024 [5]
11.5 ppm Human Expression Vector: Skin

Enzyme: ADH5 pH: Unknown Temperature: Unknown

2048 [5]
Description of the 5-HEDH concentration distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
4.88E+02 6.37E+00 7.49E+00 1.14E+00
The estimated probability distribution for 5-HEDH 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 Units Species Notes Weight Reference
1.29 kcal/mol Arabidopsis thaliana col Same reaction, no prediction available for 5-HEDH on Metacyc

Estimated Enzyme: ω-hydroxy fatty acid ω-alcohol dehydrogenase Substrate: 18-hydroxyoleate Product: 18-oxo-oleate pH: 7.3 ionic strength: 0.25

64 [6]
Description of the 5-HEDH Keq distribution
Mode Confidence Interval Location parameter (µ) Scale parameter (σ)
1.12E-01 1.00E+01 -1.39E+00 8.91E-01
The estimated probability distribution for 5-HEDH 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. ↑ Lipoxygenases in Inflammation - edited by Dieter Steinhilber
  2. ↑ 2.0 2.1 2.2 [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828885/pdf/bj4030157.pdf Karl-Rudolf ERLEMANN, Regulation of 5-hydroxyeicosanoid dehydrogenase activity in monocytic cells, Biochem. J. (2007) 403, 157–165]
  3. ↑ [http://jpet.aspetjournals.org/content/jpet/329/1/335.full.pdf Karl-Pranav Patel, Selectivity of 5-Hydroxyeicosanoid Dehydrogenase and Its Inhibition by 5-Hydroxy-Long-Chain Fatty Acids, Journal of Pharmacology and Experimental Therapeutics April 2009, 329 (1) 335-341; ]
  4. ↑ 4.0 4.1 [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]
  5. ↑ 5.0 5.1 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  6. ↑ 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
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