Difference between revisions of "Transformation of PGH2 to TXA2"

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(→‎Kmp)
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|<ref name="Orlandi1994"> [http://www.ncbi.nlm.nih.gov/pubmed/7811713 M. Orlandi, G. Bartolini, Thromboxane A2 synthase activity in platelet free human monocytes.'' Biochim Biophys Acta. 1994 Dec 8;1215(3):285-90.]</ref>   
 
|<ref name="Orlandi1994"> [http://www.ncbi.nlm.nih.gov/pubmed/7811713 M. Orlandi, G. Bartolini, Thromboxane A2 synthase activity in platelet free human monocytes.'' Biochim Biophys Acta. 1994 Dec 8;1215(3):285-90.]</ref>   
 
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|<ref name="Nusing1989"> [http://www.ncbi.nlm.nih.gov/pubmed/2195994 R. Nusing, S. Schneider-Voss and V. Ullrich, Immunoaffinity purification of human thromboxane synthase.'' Arch Biochem Biophys. 1990 Aug 1;280(2):325-30.]</ref>
 
|<ref name="Nusing1989"> [http://www.ncbi.nlm.nih.gov/pubmed/2195994 R. Nusing, S. Schneider-Voss and V. Ullrich, Immunoaffinity purification of human thromboxane synthase.'' Arch Biochem Biophys. 1990 Aug 1;280(2):325-30.]</ref>
 
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pH: 7.4
 
pH: 7.4
 
Temperature: 37
 
Temperature: 37
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|<ref name="Hecker1989"> [http://www.ncbi.nlm.nih.gov/pubmed/2491846 Hecker M.  ''On the mechanism of prostacyclin and thromboxane A2 biosynthesis.''J Biol Chem. 1989 Jan 5;264(1):141-50.]</ref>   
 
|<ref name="Hecker1989"> [http://www.ncbi.nlm.nih.gov/pubmed/2491846 Hecker M.  ''On the mechanism of prostacyclin and thromboxane A2 biosynthesis.''J Biol Chem. 1989 Jan 5;264(1):141-50.]</ref>   
 
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pH: 7.4
 
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|<ref name="Hecker1987”>[www.ncbi.nlm.nih.gov/pubmed/3579292 Hecker M. “Products, kinetics, and substrate specificity of homogeneous thromboxane synthase from human platelets: Development of a novel enzyme assay ”  Arch. Biochem. Biophys. 1987, 254, 124-135]</ref>
 
|<ref name="Hecker1987”>[www.ncbi.nlm.nih.gov/pubmed/3579292 Hecker M. “Products, kinetics, and substrate specificity of homogeneous thromboxane synthase from human platelets: Development of a novel enzyme assay ”  Arch. Biochem. Biophys. 1987, 254, 124-135]</ref>
 
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|<ref name="Haurand1985”>[www.ncbi.nlm.nih.gov/pubmed/2999104 Haurand M. “Isolation and characterization of thromboxane synthase from human platelets as a cytochrome P-450 enzyme”  J Biol Chem. 1985, 260 (5), 15059-15067]</ref>
 
|<ref name="Haurand1985”>[www.ncbi.nlm.nih.gov/pubmed/2999104 Haurand M. “Isolation and characterization of thromboxane synthase from human platelets as a cytochrome P-450 enzyme”  J Biol Chem. 1985, 260 (5), 15059-15067]</ref>
 
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|<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
 
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|<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
 
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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
 
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|<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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|<ref name="MetaCyc”>[http://metacyc.org/META/NEW-IMAGE?type=REACTION&object=THROMBOXANE-A-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=THROMBOXANE-A-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>
 
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Revision as of 10:26, 22 May 2019

Return to overview

The isomerisation of PGH2 to TXA2 is performed by TXAS. This reaction includes the rearrangement of the peroxide functional group by the protein’s heme group, whereby one oxygen is incorporated into the cyclopentane ring between C11 and C12 to form an oxane ring, whilst the other forms an epoxide group across the oxane ring between C9 and C11. This enzyme is located on the ER membrane and is a member of the cytochrome P450 family based upon the genetic sequence.

TXA2 and TXB2 bind to the TP receptor and have been found to increase T-cell proliferation (Thomas, Rocha et al. 2003). However this species is found in low concentration in the cutaneous compartment, therefore it has been deduced that the species originates from infiltrating cells from the vascular system such as leukocytes and endothelial cells (Sugimoto, Arai et al. 2006).

Reaction

R4 PGH2 -TXA4.jpg

Chemical equation

PGH2 \rightleftharpoons TXA2

Rate equation

R04.PNG

Parameters

Kms

Literature values
Value Units Species Notes Weight Reference
4.00E-03 mM Human Expression Vector: Human Monocyte

Enzyme: Platelet Free Human Monocyte pH: 7.4 Temperature: 37

2048 [1]
1.00E-02 mM Human Expression Vector: Human mirosome

Enzyme: Human Thromboxane Synthase pH:7.4 Temperature:

512 [2]
2.20E-02 mM Human Expression Vector:Human platelet

Enzyme: Human thromboxane synthase pH: 7.4 Temperature: 37

2048 [3]
Description of the TXAS Kms distribution
Mode (mM) Confidence Interval Location parameter (µ) Scale parameter (σ)
9.96E-03 2.25E+00 -3.9721 0.78374
The estimated probability distribution for TXAS 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 TXAS Kmp distribution
Mode (mM) Location parameter (µ) Scale parameter (σ)
1.03E-02 -3.942048511 0.797944323
The estimated probability distribution for TXAS 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
2687 per minute Human Expression Vector: Human Platelets

Enzyme: TXAS pH: 7.4 Temperature:30

512 [4]
1628 per minute Human Expression Vector:Platelet Microsomes

Enzyme: TXAS pH:7.4 Temperature:37

2048 [5]
Description of the TXAS kcat distribution
Mode (min-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
1.67E+03 1.25E+00 7.467597712 0.216816683
The estimated probability distribution for TXAS 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.

Enzyme concentration

Literature values
Value Units Species Notes Weight Reference
949 ppm Human Expression Vector: Platelet

Enzyme: TXAS pH: 7.5 Temperature: 37 °C

1024 [6]
56.2 ppm Human Expression Vector: Lung

Enzyme: TXAS pH: 7.5 Temperature: 37 °C

1024 [6]
4.58 ppm Human Expression Vector: Urinary Bladder

Enzyme: TXAS pH: 7.5 Temperature: 37 °C

1024 [6]
101 ppm Human Expression Vector: Oral Cavity

Enzyme: TXAS pH: 7.5 Temperature: 37 °C

1024 [7]
Description of the TXAS concentration distribution
Mode Confidence Interval Location parameter (µ) Scale parameter (σ)
7.50E+01 6.69E+00 5.66E+00 1.16E+00
The estimated probability distribution for TXAS 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
Value Units Species Notes Weight Reference
41.08 kcal/mol Not stated Estimated

Enzyme: TXAS Substrate: Arachidonate Product: TXA2 pH: 7.3 ionic strength: 0.25

64 [8]
Description of the TXAS Keq distribution
Mode Confidence Interval Location parameter (µ) Scale parameter (σ)
9.35E-01 1.00E+01 7.30E-01 8.90E-01
The estimated probability distribution for TXAS 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. ↑ M. Orlandi, G. Bartolini, Thromboxane A2 synthase activity in platelet free human monocytes. Biochim Biophys Acta. 1994 Dec 8;1215(3):285-90.
  2. ↑ R. Nusing, S. Schneider-Voss and V. Ullrich, Immunoaffinity purification of human thromboxane synthase. Arch Biochem Biophys. 1990 Aug 1;280(2):325-30.
  3. ↑ Hecker M. On the mechanism of prostacyclin and thromboxane A2 biosynthesis.J Biol Chem. 1989 Jan 5;264(1):141-50.
  4. ↑ [www.ncbi.nlm.nih.gov/pubmed/3579292 Hecker M. “Products, kinetics, and substrate specificity of homogeneous thromboxane synthase from human platelets: Development of a novel enzyme assay ” Arch. Biochem. Biophys. 1987, 254, 124-135]
  5. ↑ [www.ncbi.nlm.nih.gov/pubmed/2999104 Haurand M. “Isolation and characterization of thromboxane synthase from human platelets as a cytochrome P-450 enzyme” J Biol Chem. 1985, 260 (5), 15059-15067]
  6. ↑ 6.0 6.1 6.2 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  7. ↑ M. Wilhelm Mass-spectrometry-based draft of the human proteome Nature, 2014 509, 582–587
  8. ↑ 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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