Difference between revisions of "Degradation Pathways"
| Line 44: | Line 44: | ||
|exPGI2 | |exPGI2 | ||
|42 seconds | |42 seconds | ||
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|<ref name="Cawello1994”>[https://www.ncbi.nlm.nih.gov/pubmed/8070511 Cawello W., "Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects." Eur J Clin Pharmacol. 1994;46(3):275-7.]</ref> | |<ref name="Cawello1994”>[https://www.ncbi.nlm.nih.gov/pubmed/8070511 Cawello W., "Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects." Eur J Clin Pharmacol. 1994;46(3):275-7.]</ref> | ||
| Line 98: | Line 99: | ||
|56 | |56 | ||
|exLTB4 | |exLTB4 | ||
| + | |0.47 +/- 0.02 to 0.63 +/- 0.04 minutes | ||
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| − | | | + | |Rabbit, Immunoreactive LTB4 |
| − | | | + | |<ref name="Marleau1994”>[http://www.ncbi.nlm.nih.gov/pubmed/8075884 Marleau S., "Metabolic disposition of leukotriene B4 (LTB4) and oxidation-resistant analogues of LTB4 in conscious rabbits." Br J Pharmacol. 1994 Jun;112(2):654-8.]</ref> |
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|57 | |57 | ||
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|58 | |58 | ||
|exLTA4 | |exLTA4 | ||
| + | |3 seconds | ||
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| − | | | + | |37 degrees C |
| − | | | + | |<ref name="Zimmer2004”>[http://www.jlr.org/content/45/11/2138.long Zimmer J., "Fatty acid binding proteins stabilize leukotriene A4 competition with arachidonic acid but not other lipoxygenase products" November 2004 The Journal of Lipid Research, 45, 2138-2144.]</ref> |
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|59 | |59 | ||
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|kcal/mol | |kcal/mol | ||
|Unspecified | |Unspecified | ||
| + | | | ||
|Calculations with a Gaussian98 suite of programs | |Calculations with a Gaussian98 suite of programs | ||
Enzyme: COX (Unspecific) | Enzyme: COX (Unspecific) | ||
Revision as of 14:43, 5 September 2016
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.
| Reaction # | Species | Half Life | Rate constant | Notes | Reference |
|---|---|---|---|---|---|
| 44 | exPGF2a | 8.8 +/- 3.4 h | Study performed in decidual stromal cells and macrophages in culture. | [1] | |
| 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 | 3 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. | ||
| 48 | exPGI2 | 42 seconds | [2] | ||
| 49 | exPGE2 | 15.0 +/- 8.2 h | Study performed in decidual stromal cells and macrophages in culture. | [1] | |
| 50 | ex15-DEOXY-PGJ2 | 12 hours | Dehydration of PGD2 to ultimatley 15d-PGJ2 occurs with a half life of about 12 hours in the presense of albumin (protien found in blood). | [3] | |
| 51 | exPGJ2 | ||||
| 52 | exPGD2 | 1.5 -1.6 minutes | Human brain | [4] | |
| 53 | exPGH2 | 5 minutes | Quoted on supplier page (http://www.enzolifesciences.com/BML-PH002/prostaglandin-h2/) | ||
| 54 | ex5-OXO-ETE | 11 min | 0.0643 min-1 | Study in R15L Cells | [5] |
| 55 | ex5-HETE | ||||
| 56 | exLTB4 | 0.47 +/- 0.02 to 0.63 +/- 0.04 minutes | Rabbit, Immunoreactive LTB4 | [6] | |
| 57 | exLTC4 | ||||
| 58 | exLTA4 | 3 seconds | 37 degrees C | [7] | |
| 59 | ex5-HPETE | ||||
| 60 | ex15-HETE | 21 min | 0.0331 min-1 | Study in R15L Cells | [5] |
| 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 |
[8] |
References
- ↑ 1.0 1.1 O. Ishihara, "Differences of metabolism of prostaglandin E2 and F2 alpha by decidual stromal cells and macrophages in culture." Eicosanoids. 1991;4(4):203-7.
- ↑ Cawello W., "Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects." Eur J Clin Pharmacol. 1994;46(3):275-7.
- ↑ F. Fitzpatrick, "Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro." J Biol Chem. 1983 Oct 10;258(19):11713-8.
- ↑ Suzuki F., "Transport of prostaglandin D2 into brain." Brain Res. 1986 Oct 22;385(2):321-8.
- ↑ 5.0 5.1 Cong W., "15-oxo-Eicosatetraenoic Acid, a Metabolite of Macrophage 15-Hydroxyprostaglandin Dehydrogenase That Inhibits Endothelial Cell Proliferation" Mol Pharmacol. 2009 Sep; 76(3): 516–525.
- ↑ Marleau S., "Metabolic disposition of leukotriene B4 (LTB4) and oxidation-resistant analogues of LTB4 in conscious rabbits." Br J Pharmacol. 1994 Jun;112(2):654-8.
- ↑ Zimmer J., "Fatty acid binding proteins stabilize leukotriene A4 competition with arachidonic acid but not other lipoxygenase products" November 2004 The Journal of Lipid Research, 45, 2138-2144.
- ↑ 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
