Difference between revisions of "Transformation of PGI2 to 6-K-PGF1α"

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== Parameters ==
 
== Parameters ==
  
−
* [[Transformation of TXA2 to TXB2 |See transformation of TXA2 to TXB2]]
+
Note that the literature values are the same as * [[Transformation of TXA2 to TXB2 |reaction 6]].
 +
 
 +
== Parameters ==
 +
=== Association Rate Constant (Kf) ===
 +
 
 +
{|class="wikitable sortable"
 +
|+  style="text-align: left;" | Literature values
 +
|-
 +
! Value
 +
! Units
 +
! Conditions
 +
! Substrate
 +
! Reference
 +
|-
 +
|3.7e3 ± 0.1e3
 +
|M-1 s-1
 +
|NaCl04 (0.1 - 0.2 M)
 +
Temperature: 25°C
 +
|3
 +
|<ref name="Ross1982”>[http://pubs.acs.org/doi/pdf/10.1021/ja00370a035 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665]</ref>
 +
|-
 +
|8.7e3
 +
|M-1 s-1
 +
|KCl (1 M)
 +
Temperature: 25°C
 +
|3
 +
|<ref name="Ross1982”>[http://pubs.acs.org/doi/pdf/10.1021/ja00370a035 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665]</ref>
 +
|-
 +
|1.1e4 ± 0.1e4
 +
|M-1 s-1
 +
|NaCl04 (0.1 - 0.2 M)
 +
Temperature: 25°C
 +
|4
 +
|<ref name="Ross1982”>[http://pubs.acs.org/doi/pdf/10.1021/ja00370a035 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665]</ref>
 +
|-
 +
|2.4 e4
 +
|M-1 s-1
 +
|KCl (1M)
 +
Temperature: 25°C
 +
|4
 +
|<ref name="Ross1982”>[http://pubs.acs.org/doi/pdf/10.1021/ja00370a035 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665]</ref>
 +
|-
 +
|3.7e3 ± 0.1e3
 +
|M-1 s-1
 +
|NaCl04 (0.1 - 0.2 M)
 +
Temperature: 25°C
 +
|5
 +
|<ref name="Ross1982”>[http://pubs.acs.org/doi/pdf/10.1021/ja00370a035 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665]</ref>
 +
|-
 +
|3.6 ± 0.2
 +
|M-1 s-1
 +
|NaCl04 (0.1 - 0.2 M)
 +
Temperature: 25°C
 +
|6
 +
|<ref name="Ross1982”>[http://pubs.acs.org/doi/pdf/10.1021/ja00370a035 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665]</ref>
 +
|-
 +
|1.7 ± 0.1
 +
|M-1 s-1
 +
|NaCl04 (0.1 - 0.2 M)
 +
Temperature: 25°C
 +
|7
 +
|<ref name="Ross1982”>[http://pubs.acs.org/doi/pdf/10.1021/ja00370a035 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665]</ref>
 +
|-
 +
|26.7 ± 0.9
 +
|M-1 s-1
 +
|NaCl04 (0.1 - 0.2 M)
 +
Temperature: 25°C
 +
|8
 +
|<ref name="Ross1982”>[http://pubs.acs.org/doi/pdf/10.1021/ja00370a035 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665]</ref>
 +
|-
 +
|35
 +
|M-1 s-1
 +
|KCl (1M)
 +
Temperature: 25°C
 +
|8
 +
|<ref name="Ross1982”>[http://pubs.acs.org/doi/pdf/10.1021/ja00370a035 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665]</ref>
 +
|-
 +
| 2.25 ± 0.12
 +
| M-1 min-1
 +
| 25°C, in imidazole buffer and also in phosphate buffers,
 +
| CO2 to H2CO3
 +
| <ref name="Gibbons1963”>[http://www.jbc.org/content/238/10/3502.full.pdf B. Gibbons "Rate of Hydration of Carbon Dioxide and Dehydration of Carbonic Acid at 25" J Biol Chem. 1963 Oct;238:3502-7]</ref>
 +
|-
 +
|}
 +
 
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | Description of the reaction 7 Kf distribution
 +
! Mode (M-1 s-1) !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ)
 +
|-
 +
| 3.70E+03 || 3.44E+01 || 1.10E+01 || 1.66E+00
 +
|}
 +
 
 +
[[Image:23.jpg|none|thumb|500px|The estimated probability distribution for reaction 7 Kf. 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.  ]]
 +
 
 +
=== Dissociation Rate Constant (Kr) ===
 +
This is a “Dependent parameter”, meaning that the log-normal distribution for this parameter was calculated using multivariate distributions  (this is discussed in detail[[Quantification of parameter uncertainty | here]]). As a result, no confidence interval factor or literature values were cited for this parameter. 
 +
 
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | Description of the reaction 7 Kr distribution
 +
! Mode !! Location parameter (µ) !! Scale parameter (σ)
 +
|-
 +
| 5.28E+01 || 5.63E+00 || 1.29E+00
 +
|}
 +
 
 +
[[Image:24.jpg|none|thumb|500px|The estimated probability distribution for reaction 6 Kr. 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.  ]]
 +
 
 +
=== Dissociation Constant ===
 +
{|class="wikitable sortable"
 +
|+  style="text-align: left;" | Literature values
 +
|-
 +
! Value
 +
! Units
 +
! Conditions
 +
! Substrate
 +
! Reference
 +
|-
 +
|0.000038
 +
|mM
 +
|Temperature: 35°C
 +
Vector:Mosquito
 +
 
 +
Note: "In solution, it undergoes rapid hydrolysis to form TXB2, a stable but physiologically inactive compound." - therefore they used stable analogues.
 +
|carbocyclic TXA2 (analogue of TXA2)
 +
|<ref name="Alvarenga2010”>[http://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1000547&type=printable P. H. Alvarenga "The Function and Three-Dimensional Structure of a Thromboxane A2/Cysteinyl Leukotriene-Binding Protein from the Saliva of a Mosquito Vector of the Malaria Parasite" PLoS Biol. 2010 Nov 30;8(11):e1000547. doi: 10.1371/journal.pbio.1000547.]</ref>
 +
|-
 +
|0.00000023
 +
|mM
 +
|Temperature: 35°C
 +
Vector:Rabbit cultured astrocytes
 +
 
 +
Note: "In solution, it undergoes rapid hydrolysis to form TXB2, a stable but physiologically inactive compound." - therefore they used stable analogues.
 +
|[3H]IONO NT-126, a TXA z antagonist,
 +
|<ref name="Nakahata1992”>[http://ac.els-cdn.com/S0006899310800137/1-s2.0-S0006899310800137-main.pdf?_tid=b2ab095e-155f-11e7-94f0-00000aab0f26&acdnat=1490888822_58d1d45dc3238dede94e4a2f15cada82 N Nakahata et al. "The Presence of Thromboxane A2 Receptors in Cultured Astrocytes From Rabbit Brain" Brain Res 583 (1-2), 100-104. 1992 Jun 26]</ref>
 +
|-
 +
|1500 ± 500 (excluded)
 +
|mM
 +
|Temperature: 25°C
 +
In vitro
 +
|Hydroxysulfamic acid
 +
[[File:HSA.PNG ‎|center|500px]]
 +
|<ref name="Littlejohn1989”>[http://www.nrcresearchpress.com/doi/pdf/10.1139/v89-243 D. LITTLEJOHN "The dissociation constant and acid hydrolysis rate of hydroxysulfamic acid"  Can. J. Chem. 67, 1596 (1989).]</ref>
 +
|-
 +
|[[File:H202.PNG ‎|center|500px]]
 +
|N/A
 +
|Temperature: 20°C
 +
In vitro
 +
|H2O2
 +
|<ref name="Littlejohn1989”>[http://pubs.rsc.org/-/content/articlepdf/1949/tf/tf9494500224  M. G. EVAN "The dissociation constant and acid hydrolysis rate of hydroxysulfamic acid"  Trans. Faraday Soc., 1949,45, 224-230]</ref>
 +
|-
 +
|5.9 E-8
 +
|N/A
 +
|Oxaliplatin
 +
|[[File:Oxaliplatin.PNG ‎|center|500px]]
 +
|<ref name="Jerremalm”>[http://www.sciencedirect.com/science/article/pii/S0022354916311649  Elin Jerremalm "Hydrolysis of Oxaliplatin—Evaluation of the Acid Dissociation Constant for the Oxalato Monodentate Complex"  Journal of Pharmaceutical Sciences Volume 92, Issue 2, February 2003, Pages 436–438]</ref>
 +
|-
 +
|}
 +
 
 +
{| class="wikitable"
 +
|+  style="text-align: left;" | Description of the reaction 7 KD distribution
 +
! Mode (M-1 s-1) !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ)
 +
|-
 +
| 2.35E-07 || 1.76E+04 || -6.86E+00 || 2.90E+00
 +
|}
 +
 
 +
[[Image:R7 KD.jpg|none|thumb|500px|The estimated probability distribution for reaction 6 Kr. 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 ==
 
* [[Transformation of PGH2 to PGI2 |Transformation of PGH2 to PGI2]]
 
* [[Transformation of PGH2 to PGI2 |Transformation of PGH2 to PGI2]]

Revision as of 08:46, 15 May 2019

Return to overview

Due to ring strain, PGI2 is rapidly hydrolysed to 6-keto-PGF1a. This is a non-enzymatic reaction and results in the formation of a hydroxyl group at C9 and a ketone at C6, by incorporating two hydrogens and one oxygen.

Reaction

R7 PGI2 - K6PGF2A.jpg

Chemical equation

PGI2 \rightleftharpoons 6-K-PGF1α

Rate equation

R07.PNG

Parameters

Note that the literature values are the same as * reaction 6.

Parameters

Association Rate Constant (Kf)

Literature values
Value Units Conditions Substrate Reference
3.7e3 ± 0.1e3 M-1 s-1 NaCl04 (0.1 - 0.2 M)

Temperature: 25°C

3 [1]
8.7e3 M-1 s-1 KCl (1 M)

Temperature: 25°C

3 [1]
1.1e4 ± 0.1e4 M-1 s-1 NaCl04 (0.1 - 0.2 M)

Temperature: 25°C

4 [1]
2.4 e4 M-1 s-1 KCl (1M)

Temperature: 25°C

4 [1]
3.7e3 ± 0.1e3 M-1 s-1 NaCl04 (0.1 - 0.2 M)

Temperature: 25°C

5 [1]
3.6 ± 0.2 M-1 s-1 NaCl04 (0.1 - 0.2 M)

Temperature: 25°C

6 [1]
1.7 ± 0.1 M-1 s-1 NaCl04 (0.1 - 0.2 M)

Temperature: 25°C

7 [1]
26.7 ± 0.9 M-1 s-1 NaCl04 (0.1 - 0.2 M)

Temperature: 25°C

8 [1]
35 M-1 s-1 KCl (1M)

Temperature: 25°C

8 [1]
2.25 ± 0.12 M-1 min-1 25°C, in imidazole buffer and also in phosphate buffers, CO2 to H2CO3 [2]
Description of the reaction 7 Kf distribution
Mode (M-1 s-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
3.70E+03 3.44E+01 1.10E+01 1.66E+00
The estimated probability distribution for reaction 7 Kf. 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.

Dissociation Rate Constant (Kr)

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 reaction 7 Kr distribution
Mode Location parameter (µ) Scale parameter (σ)
5.28E+01 5.63E+00 1.29E+00
The estimated probability distribution for reaction 6 Kr. 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.

Dissociation Constant

Literature values
Value Units Conditions Substrate Reference
0.000038 mM Temperature: 35°C

Vector:Mosquito

Note: "In solution, it undergoes rapid hydrolysis to form TXB2, a stable but physiologically inactive compound." - therefore they used stable analogues.

carbocyclic TXA2 (analogue of TXA2) [3]
0.00000023 mM Temperature: 35°C

Vector:Rabbit cultured astrocytes

Note: "In solution, it undergoes rapid hydrolysis to form TXB2, a stable but physiologically inactive compound." - therefore they used stable analogues.

[3H]IONO NT-126, a TXA z antagonist, [4]
1500 ± 500 (excluded) mM Temperature: 25°C

In vitro

Hydroxysulfamic acid
HSA.PNG
 [5]
H202.PNG
 N/A Temperature: 20°C

In vitro

H2O2 [5]
5.9 E-8 N/A Oxaliplatin
Oxaliplatin.PNG
 [6]
Description of the reaction 7 KD distribution
Mode (M-1 s-1) Confidence Interval Location parameter (µ) Scale parameter (σ)
2.35E-07 1.76E+04 -6.86E+00 2.90E+00
The estimated probability distribution for reaction 6 Kr. 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

  • ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 A. Ross "Vinyl epoxide hydrolysis reactions" J. Am. Chem. Soc., 1982, 104 (6), pp 1658–1665
  • ↑ B. Gibbons "Rate of Hydration of Carbon Dioxide and Dehydration of Carbonic Acid at 25" J Biol Chem. 1963 Oct;238:3502-7
  • ↑ P. H. Alvarenga "The Function and Three-Dimensional Structure of a Thromboxane A2/Cysteinyl Leukotriene-Binding Protein from the Saliva of a Mosquito Vector of the Malaria Parasite" PLoS Biol. 2010 Nov 30;8(11):e1000547. doi: 10.1371/journal.pbio.1000547.
  • ↑ N Nakahata et al. "The Presence of Thromboxane A2 Receptors in Cultured Astrocytes From Rabbit Brain" Brain Res 583 (1-2), 100-104. 1992 Jun 26
  • ↑ 5.0 5.1 D. LITTLEJOHN "The dissociation constant and acid hydrolysis rate of hydroxysulfamic acid" Can. J. Chem. 67, 1596 (1989). Cite error: Invalid <ref> tag; name "Littlejohn1989.E2.80.9D" defined multiple times with different content
  • ↑ Elin Jerremalm "Hydrolysis of Oxaliplatin—Evaluation of the Acid Dissociation Constant for the Oxalato Monodentate Complex" Journal of Pharmaceutical Sciences Volume 92, Issue 2, February 2003, Pages 436–438
    • Retrieved from ‘http://www.systemsbiology.ls.manchester.ac.uk/wiki/index.php?title=Transformation_of_PGI2_to_6-K-PGF1α&oldid=6613’