Difference between revisions of "Transformation of TXA2 to TXB2"

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== Parameters ==
 
== Parameters ==
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=== Association Rate Constant (Kf) ===
  
 
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{| class="wikitable"
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|+  style="text-align: left;" | Dissociation Rate Constant (Kr)
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|+  style="text-align: left;" | Description of the reaction 6 Kf distribution
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! Mode (M-1 s-1) !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ)
 
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! Value
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| 3.70E+03 || 3.44E+01 || 1.10E+01 || 1.66E+00
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! Units
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! Conditions
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! Substrate
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[[Image:21.jpg|none|thumb|500px|The estimated probability distribution for reaction 6 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.  ]]
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! Reference
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|-
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=== Dissociation Rate Constant (Kr) ===
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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. 
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{| class="wikitable"
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|+  style="text-align: left;" | Description of the reaction 6 Kr distribution
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! Mode !! Location parameter (µ) !! Scale parameter (σ)
 
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|-
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| 5.28E+01 || 5.63E+00 || 1.29E+00
 
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|}
  
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[[Image:22.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.  ]]
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=== Dissociation Constant ===
 
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|+  style="text-align: left;" | Literature values
 
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{| class="wikitable"
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|+  style="text-align: left;" | Description of the reaction 6 KD distribution
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! Mode (M-1 s-1) !! Confidence Interval !! Location parameter (µ) !! Scale parameter (σ)
 +
|-
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| 2.35E-07 || 1.76E+04 || -6.86E+00 || 2.90E+00
 +
|}
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[[Image:R6 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 ==

Revision as of 08:37, 15 May 2019

Return to overview

Thromboxane A2 is a bioactive molecule which affects vasoactivity and promotes thrombosis. It is unstable due to the epoxide functional group, and as a consequence has a short half-life of 20- 30 seconds. The hydrolysis reaction results in the generation of biologically inactive TXB2.

Reaction

R6 TXA2 - TXB2.jpg

Chemical equation

TXA2 \rightleftharpoons TXB2

Rate equation

R06.PNG

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 6 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 6 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 6 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 6 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

References

  1. ↑ 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
  2. ↑ B. Gibbons "Rate of Hydration of Carbon Dioxide and Dehydration of Carbonic Acid at 25" J Biol Chem. 1963 Oct;238:3502-7
  3. ↑ 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.
  4. ↑ 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. ↑ 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
  6. ↑ 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
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