Difference between revisions of "Degradation Pathways"

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[[Welcome to the In-Silico Model of Cutaneous Lipids Wiki | Return to overview]]
 
[[Welcome to the In-Silico Model of Cutaneous Lipids Wiki | Return to overview]]
  
Upon being transported out of the cell, the eicosanoids accumulate in the interstitial fluid, which for simplicity is referred to as the extracellular compartment in the model. A decay constant was included for each extracellular metabolite to represent degradation. To describe the breaking down of metabolites an irreversible mass action rate law was used for reactions 43-64. The half life of each eicosanoid was initially assumed as 24 hours, but will be made metabolite specific when all of the values have been collected.  
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To account for the decay in metabolite concentration over time, there are 46 decay reactions in this network. In these reactions, the product mass is pooled together under the term “Miscellaneous metabolites”. This is a collective term which refers to metabolites which are no longer of interest to this work, for example they are exported to the systemic circulation or undergo degradation. To account for the different rate of metabolite decay in the intracellular and extracellular compartments, each metabolite has two decay reactions which are governed by independent parameters.
  
{|class="wikitable sortable"
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To calculate the rate constant, the following equation was used:
|+  style="text-align: left;" | Degradation Pathways
+
<math> k = ln(2)/t(0.5) </math>
|-
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! Reaction #
+
{|width ="80%"
! Species
 
! Half Life
 
! Rate constant
 
! Notes
 
! Reference
 
|-
 
|44
 
|exPGF2a
 
|
 
|
 
|
 
|
 
|-
 
|45
 
|exTXB2
 
|20 - 30 minutes
 
|
 
|Quoted in a textbook(https://books.google.co.uk/books?id=_9kEeTjyJdMC&pg=PA864&lpg=PA864&dq=half+life+txa2&source=bl&ots=2OTF4Mh2Jk&sig=hu79GprliUcW4QE_Zm79islesOA&hl=en&sa=X&ved=0ahUKEwj0oo2sgfjOAhXLIcAKHcaPDHQQ6AEIRjAI#v=onepage&q=half%20life%20txa2&f=false) with no ref.
 
|
 
|-
 
|46
 
|exTXA2
 
|20 - 30 seconds
 
|
 
|Quoted in a textbook(https://books.google.co.uk/books?id=_9kEeTjyJdMC&pg=PA864&lpg=PA864&dq=half+life+txa2&source=bl&ots=2OTF4Mh2Jk&sig=hu79GprliUcW4QE_Zm79islesOA&hl=en&sa=X&ved=0ahUKEwj0oo2sgfjOAhXLIcAKHcaPDHQQ6AEIRjAI#v=onepage&q=half%20life%20txa2&f=false) with no ref.
 
|
 
|-
 
|47
 
|ex6-KETO-PGF2A
 
|
 
|
 
|
 
|
 
|-
 
|48
 
|exPGI2
 
|
 
|
 
|
 
|
 
|-
 
|49
 
|exPGE2
 
|
 
|
 
|
 
|
 
|-
 
|50
 
|ex15-DEOXY-PGJ2
 
|
 
|
 
|
 
|
 
|-
 
|51
 
|exPGJ2
 
 
|
 
|
|
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* [[Decay of AA to exAA|Decay of AA/exAA (R64/72) ]]
|
+
* [[Decay of PGI2 to exPGI2 |Decay of PGI<sub>2</sub>/exPGI<sub>2</sub> (R48/77) ]]
|
+
* [[Decay of PGE2 to exPGE2 |Decay of PGE<sub>2</sub>/exPGE<sub>2</sub>  (R49/76) ]]
|-
+
* [[Decay of PGF2a/exPGF2a |Decay of PGF<sub>2a</sub>/exPGF<sub>2a</sub> (R44/74) ]]
|52
+
* [[Decay of PGH2 to exPGH2 |Decay of PGH<sub>2</sub>/exPGH<sub>2</sub> (R53/73)  ]]
|exPGD2
+
* [[Decay of PGD2 to exPGD2 |Decay of PGD<sub>2</sub>/exPGD<sub>2</sub> (R52/78) ]]
|
+
* [[Decay of PGJ2 to exPGJ2 |Decay of PGJ<sub>2</sub>/exPGJ<sub>2</sub> (R51/83) ]]
|
+
* [[Decay of TXB2/exTXB2 |Decay of TXB<sub>2</sub>/exTXB<sub>2</sub> (R45/81) ]]
|
+
* [[Decay of TXA2 to exTXA2 |Decay of TXA<sub>2</sub>/exTXA<sub>2</sub> (R46/75) ]]
|
+
* [[Decay of K6PGF2a to exK6PGF2a  |Decay of 6-keto-PGF<sub>1a</sub>/ex6-keto-PGF<sub>1a</sub> (R47/82)]]
|-
+
* [[Decay of D15PGJ2 to exD15PGJ2 |Decay of 15-deoxy-PGJ<sub>2</sub>/ex15-deoxy-PGJ<sub>2</sub> (R50/84) ]]
|53
+
* [[Decay of 15-Keto-PGE2 to ex15-Keto-PGE2  |Decay of 15-keto-PGE<sub>2</sub>/ex15-keto-PGE<sub>2</sub> (R68/79)]]
|exPGH2
+
* [[Decay of 3,4-Dihydro-15-Keto-PGE2  to ex3,4-Dihydro-15-Keto-PGE2  |Decay of 13,14-dihydro-15-keto-PGE<sub>2</sub>/ex13,14-dihydro-15-keto-PGE<sub>2</sub> (R71/80)]]
|
+
* [[Decay of 5-Oxo-ETE to ex5-Oxo-ETE |Decay of 5-oxo-ETE/ex5-oxo-ETE  (R54/91) ]]
|
+
* [[Decay of LTB4 to exLTB4 |Decay of LTB<sub>4</sub>/exLTB<sub>4</sub> (R56/93) ]]
|
+
* [[Decay of LTC4 to exLTC4 |Decay of LTC<sub>4</sub>/exLTC<sub>4</sub> (R57/94) ]]
|
+
* [[Decay of LTA4 to exLTA4 |Decay of LTA<sub>4</sub>/exLTA<sub>4</sub> (R58/92) ]]
|-
+
* [[Decay of 12-HPETE to ex12-HPETE |Decay of 12-HPETE/ex12-HPETE (R63/86) ]]
|54
+
* [[Decay of 15-HPETE to ex15-HPETE |Decay of 15-HPETE/ex15-HPETE (R61/85)]]
|ex5-OXO-ETE
+
* [[Decay of 5-HPETE to ex5-HPETE |Decay of 5-HPETE/ex5-HPETE (R59/87) ]]
|
+
* [[Decay of 5-HETE to ex5-HETE |Decay of 5-HETE/ex5-HETE (R55/90) ]]
|
+
* [[Decay of 15-HETE to ex15-HETE |Decay of 15-HETE/ex15-HETE (R60/88) ]]
|
+
* [[Decay of 12-HETE to ex12-HETE |Decay of 12-HETE/ex12-HETE (R62/89) ]]
|
 
|-
 
|55
 
|ex5-HETE
 
|
 
|
 
|
 
|
 
|-
 
|56
 
|exLTB4
 
|
 
|
 
|
 
|
 
|-
 
|57
 
|exLTC4
 
|
 
|
 
|
 
|
 
|-
 
|58
 
|exLTA4
 
|
 
|
 
|
 
|
 
|-
 
|59
 
|ex5-HPETE
 
|
 
|
 
|
 
|
 
|-
 
|60
 
|ex15-HETE
 
|
 
|
 
|
 
|
 
|-
 
|61
 
|ex15-HPETE
 
|
 
|
 
|
 
|
 
|-
 
|62
 
|ex12-HETE
 
|
 
|
 
|
 
|
 
|-
 
|63
 
|ex12-HPETE
 
|
 
|
 
|
 
|
 
|-
 
|64
 
|exAA
 
|
 
|
 
|
 
|
 
|-
 
|(-30)
 
|kcal/mol
 
|Unspecified
 
|Calculations with a Gaussian98 suite of programs
 
Enzyme: COX (Unspecific)
 
Substrate: Arachidonate
 
Temperature: 298.15 K
 
Pressure: 1 bar
 
|<ref name="Silva2003”>[http://link.springer.com/article/10.1007/s00214-003-0476-9 P. Silva, "A theoretical study of radical-only and combined radical/carbocationic mechanisms of arachidonic acid cyclooxygenation by prostaglandin H synthase" Theor Chem Acc (2003) 110: 345]</ref>
 
|-
 
 
|}
 
|}
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== References ==
 +
<references/>

Latest revision as of 09:51, 17 May 2019

Return to overview

To account for the decay in metabolite concentration over time, there are 46 decay reactions in this network. In these reactions, the product mass is pooled together under the term “Miscellaneous metabolites”. This is a collective term which refers to metabolites which are no longer of interest to this work, for example they are exported to the systemic circulation or undergo degradation. To account for the different rate of metabolite decay in the intracellular and extracellular compartments, each metabolite has two decay reactions which are governed by independent parameters.

To calculate the rate constant, the following equation was used:  k = ln(2)/t(0.5)


References