View source for Transformation of PGI2 to 6-K-PGF1α

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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 ==
[[File:R7_PGI2_-_K6PGF2A.jpg ‎|center|500px]]

==Chemical equation==

<center><math> PGI2 \rightleftharpoons 6-K-PGF1α </math></center>

== Rate equation ==

[[File:R07.PNG ‎|center|500px]]

== Parameters ==

Note that the literature values are the same as [[Transformation of TXA2 to TXB2 |reaction 6]].

=== Association Rate Constant (Kf) ===

{|class="wikitable sortable" 
|+  style="text-align: left;" | Literature values
|-
! Value
! Units
! Conditions
! Substrate
! Weight
! Reference
|-
|3.7e3 ± 0.1e3
|M-1 s-1
|NaCl04 (0.1 - 0.2 M)
Temperature: 25°C
|3
|32
|<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
|32
|<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
|48
|<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
|48
|<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
|32
|<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
|32
|<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
|32
|<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
|32
|<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
|32
|<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
|32
| <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
! Weight
! 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)
|24
|<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,
|36
|<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]]
|16
|<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
|16
|<ref name="Evan1939”>[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]]
|16
|<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 ==
* [[Transformation of PGH2 to PGI2 |Transformation of PGH2 to PGI2]]

== References ==