Difference between revisions of "Transformation of PGH2 to PGF2α"

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(→‎Kmp)
(→‎Enzyme Parameters)
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! Species
 
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|Human  
 
|Human  
 
|Placental Aldose Reductase (AKR1B1), E. Coli, pH 7, 37°C
 
|Placental Aldose Reductase (AKR1B1), E. Coli, pH 7, 37°C
 +
|512
 
|<ref name="Kabututu2009"> [http://www.ncbi.nlm.nih.gov/pubmed/19010934 Z. Kabututu, M. Manin, Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7.'' J Biochem 2009,145(2):161-8)]</ref>  
 
|<ref name="Kabututu2009"> [http://www.ncbi.nlm.nih.gov/pubmed/19010934 Z. Kabututu, M. Manin, Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7.'' J Biochem 2009,145(2):161-8)]</ref>  
 
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|Human  
 
|Human  
 
|Lung PGF2a Synthase (AKR1C3), E. Coli, pH 7, 37°C
 
|Lung PGF2a Synthase (AKR1C3), E. Coli, pH 7, 37°C
 +
| 512
 
|<ref name="Kabututu2009"> [http://www.ncbi.nlm.nih.gov/pubmed/19010934 Z. Kabututu, M. Manin, Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7.'' J Biochem 2009,145(2):161-8)]</ref>  
 
|<ref name="Kabututu2009"> [http://www.ncbi.nlm.nih.gov/pubmed/19010934 Z. Kabututu, M. Manin, Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7.'' J Biochem 2009,145(2):161-8)]</ref>  
 
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| Prostamide/PGF Synthase Purified
 
| Prostamide/PGF Synthase Purified
 
from Swine Brain and of Murine Enzyme Expressed in E. coli
 
from Swine Brain and of Murine Enzyme Expressed in E. coli
 +
|128
 
| <ref name="Moriuchi2008"> [http://www.ncbi.nlm.nih.gov/pubmed/18006499 Moriuchi H., Molecular characterization of a novel type of prostamide/prostaglandin F synthase, belonging to the thioredoxin-like superfamily.'' J Biol Chem. 2008 Jan 11;283(2):792-801.)]</ref>  
 
| <ref name="Moriuchi2008"> [http://www.ncbi.nlm.nih.gov/pubmed/18006499 Moriuchi H., Molecular characterization of a novel type of prostamide/prostaglandin F synthase, belonging to the thioredoxin-like superfamily.'' J Biol Chem. 2008 Jan 11;283(2):792-801.)]</ref>  
 
|}
 
|}
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pH: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
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|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: 7.5
 
pH: 7.5
 
Temperature: 37 °C
 
Temperature: 37 °C
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|1024
 
|<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>
 
|<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>
 
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|-
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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 human proteome'' Nature, 2014 509, 582–587]</ref>
 
|<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>
 
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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 human proteome'' Nature, 2014 509, 582–587]</ref>
 
|<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>
 
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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”>[http://metacyc.org/META/NEW-IMAGE?type=REACTION&object=PROSTAGLANDIN-E-SYNTHASE-RXN 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=PROSTAGLANDIN-E-SYNTHASE-RXN 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>
  

Revision as of 09:20, 22 May 2019

Return to overview

The isomerisation of PGH2 to PGF2a is performed by PGFS. This reaction results in the formation of two hydroxyl groups at C9 and C11. This reaction takes place in the cytosol of cells and the cofactor is NADPH. PGFS is found to also catalyse the conversion of aldehydes and ketones to PGF2a, for example the conversion of PGD2 to PGF2a.

PGF2α has been found to be produced by keratinocyte cells in vitro (Rhodes, Gledhill et al. 2009). This species is synthesised from PGH2 via the prostaglandin F synthase (PGFS) or the PGE 9-ketoreductase enzymes. Upon production this species have been associated with pigmentation, inflammation and hair growth in the skin (Scott, Leopardi et al. 2004, Scott, Fricke et al. 2007). The species has various inflammatory roles such as a pro-inflammatory effect upon the system by facilitating pain transmission (Murata, Ushikubi et al. 1997) and also an anti-inflammatory effect by inhibiting lymphocyte and endothelial cell interactions (Della Bella, Molteni et al. 2001).

Reaction

R3 PGH2 -PGF2A.jpg

Chemical equation

PGH2 \rightleftharpoons PGF2a

Rate equation

R03.PNG

Enzyme Parameters

Kms

Literature values
Value Units Species Notes Weight Reference
1.90E-03 ± 1.5E-03 mM Human Placental Aldose Reductase (AKR1B1), E. Coli, pH 7, 37°C 512 [1]
1.80E-02 mM Human Lung PGF2a Synthase (AKR1C3), E. Coli, pH 7, 37°C 512 [1]
Description of the PGFS Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.33E-02 3.81E+00 -3.45E+00 9.33E-01
The estimated probability distribution for PGFS 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 PGFS Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
1.46E-02 -2.86E+00 1.17E+00
The estimated probability distribution for PGFS 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
14.9 per minute Mouse/Swine Prostamide/PGF Synthase Purified

from Swine Brain and of Murine Enzyme Expressed in E. coli

128 [2]
Description of the PGFS kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.48E+01 1.10E+00 2.71E+00 9.49E-02
The estimated probability distribution for PGFS 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
105 ppm Human Expression Vector: Platelet

Enzyme: PGFS pH: 7.5 Temperature: 37 °C

1024 [3]
19.9 ppm Human Expression Vector: Lung

Enzyme: PGFS pH: 7.5 Temperature: 37 °C

1024 [4]
40.3 ppm Human Expression Vector: Esophagus

Enzyme: PGFS pH: 7.5 Temperature: 37 °C

1024 [4]
110 ppm Human Expression Vector: Oral Cavity

Enzyme: PGFS pH: 7.5 Temperature: 37 °C

1024 [4]
Description of the PGFS concentration distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
6.41E+01 2.05E+00 4.53E+00 6.06E-01


The estimated probability distribution for PGFS 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

Gibbs Free Energy Change
Value Units Species Notes Reference
kcal/mol Not stated Estimated

Enzyme: PGFS Substrate: Arachidonate Product: PGF2a pH: 7.3 ionic strength: 0.25

64 [5]
Mode Confidence Interval Location parameter (µ) Scale parameter (σ)
7.46E+04 1.00E+01 1.20E+01 8.90E-01
The estimated probability distribution for PGFS 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.

References

  1. ↑ 1.0 1.1 Z. Kabututu, M. Manin, Prostaglandin F2alpha synthase activities of aldo-keto reductase 1B1, 1B3 and 1B7. J Biochem 2009,145(2):161-8)
  2. ↑ Moriuchi H., Molecular characterization of a novel type of prostamide/prostaglandin F synthase, belonging to the thioredoxin-like superfamily. J Biol Chem. 2008 Jan 11;283(2):792-801.)
  3. ↑ M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  4. ↑ 4.0 4.1 4.2 M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  5. ↑ 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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