Difference between revisions of "Degradation Pathways"
Line 5: | Line 5: | ||
Pseudo-first order reactions. | Pseudo-first order reactions. | ||
− | {|class="wikitable | + | |
− | | | + | {| class="wikitable" |
+ | ! style="text-align: center; font-weight: bold;" | Reaction # | ||
+ | ! style="text-align: center; font-weight: bold;" | Species | ||
+ | ! style="text-align: center; font-weight: bold;" | Half Life (min) | ||
+ | ! style="text-align: center; font-weight: bold;" | Rate constant(min -1) | ||
+ | ! style="text-align: center; font-weight: bold;" | Notes | ||
+ | ! style="text-align: center; font-weight: bold;" | Reference | ||
|- | |- | ||
− | + | | style="text-align: center;" | 44 | |
− | + | | style="text-align: center;" | exPGF2a | |
− | + | | style="text-align: center;" | 528 ± 204 | |
− | + | | style="text-align: center;" | 0.001 ± 0.003 | |
− | + | | style="text-align: center;" |Study performed in decidual stromal cells and macrophages in culture. | |
− | + | | style="text-align: center;" | <ref name="Ishihara1991”>[http://www.ncbi.nlm.nih.gov/pubmed/1789996 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.]</ref> | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 45 |
− | | | + | | style="text-align: center;" | exTXB2 |
− | | | + | | style="text-align: center;" | 20 to 30 |
− | | | + | | style="text-align: center;" | 0.035 to 0.023 |
− | | | + | | style="text-align: center;" |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. |
− | | | + | | style="text-align: center;" | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 46 |
− | | | + | | style="text-align: center;" | exTXA2 |
− | | | + | | style="text-align: center;" | 0.333 |
− | | | + | | style="text-align: center;" | 2.079 |
− | |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. | + | | style="text-align: center;" |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. |
− | | | + | | style="text-align: center;" | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 47 |
− | | | + | | style="text-align: center;" | ex6-KETO-PGF2A |
− | | | + | | style="text-align: center;" | 3 |
− | | | + | | style="text-align: center;" | 0.231 |
− | |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. | + | | style="text-align: center;" |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. |
− | | | + | | style="text-align: center;" | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 48 |
− | | | + | | style="text-align: center;" | exPGI2 |
− | | | + | | style="text-align: center;" | 0.7 |
− | | | + | | style="text-align: center;" | 0.990 |
− | | | + | | style="text-align: center;" | |
− | + | | style="text-align: center;" |<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> | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 49 |
− | | | + | | style="text-align: center;" | exPGE2 |
− | | | + | | style="text-align: center;" | 900,± 492 |
− | | | + | | style="text-align: center;" | 0.001 ± 0.001 |
− | | | + | | style="text-align: center;" | Study performed in decidual stromal cells and macrophages in culture. |
− | |<ref name=" | + | | style="text-align: center;" | <ref name="Ishihara1991”>[http://www.ncbi.nlm.nih.gov/pubmed/1789996 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.]</ref> |
|- | |- | ||
− | | | + | | style="text-align: center;" | 50 |
− | | | + | | style="text-align: center;" | ex15-DEOXY-PGJ2 |
− | | | + | | style="text-align: center;" | 720 |
− | | | + | | style="text-align: center;" | 0.001 |
− | | | + | | style="text-align: center;" | 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). |
− | |<ref name=" | + | | style="text-align: center;" | <ref name="Fitzpatrick1983”>[http://www.ncbi.nlm.nih.gov/pubmed/6578214 F. Fitzpatrick, "Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro." J Biol Chem. 1983 Oct 10;258(19):11713-8.]</ref> |
|- | |- | ||
− | | | + | | style="text-align: center;" | 51 |
− | | | + | | style="text-align: center;" | exPGJ2 |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 52 |
− | | | + | | style="text-align: center;" | exPGD2 |
− | | | + | | style="text-align: center;" | 1.5 - 1.6 |
− | | | + | | style="text-align: center;" | 0.462 to 0.433 |
− | | | + | | style="text-align: center;" | Human brain |
− | | | + | | style="text-align: center;" | <ref name="Suzuki1986”>[http://www.ncbi.nlm.nih.gov/pubmed/3465420 Suzuki F., "Transport of prostaglandin D2 into brain." Brain Res. 1986 Oct 22;385(2):321-8.]</ref> |
|- | |- | ||
− | | | + | | style="text-align: center;" | 53 |
− | | | + | | style="text-align: center;" | exPGH2 |
− | | | + | | style="text-align: center;" | 5 |
− | | | + | | style="text-align: center;" | 0.139 |
− | | | + | | style="text-align: center;" | Quoted on supplier page (http://www.enzolifesciences.com/BML-PH002/prostaglandin-h2/) |
− | | | + | | style="text-align: center;" | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 54 |
− | | | + | | style="text-align: center;" | ex5-OXO-ETE |
− | | | + | | style="text-align: center;" | 11 |
− | | | + | | style="text-align: center;" | 0.064 |
− | | | + | | style="text-align: center;" | Study in R15L Cells |
− | + | | style="text-align: center;" | <ref name="Cong2009”>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730384/ 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.]</ref> | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 55 |
− | |ex5- | + | | style="text-align: center;" | ex5-HETE |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 56 |
− | | | + | | style="text-align: center;" | exLTB4 |
− | | | + | | style="text-align: center;" | 0.47 ± 0.02 to 0.63 ± 0.04 |
− | | | + | | style="text-align: center;" | 1.475 ± 34.657 to 1.100 ± 17.329 |
− | | | + | | style="text-align: center;" | Rabbit, Immunoreactive LTB4 |
− | | | + | | style="text-align: center;" | <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> |
|- | |- | ||
− | | | + | | style="text-align: center;" | 57 |
− | | | + | | style="text-align: center;" | exLTC4 |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 58 |
− | | | + | | style="text-align: center;" | exLTA4 |
− | | | + | | style="text-align: center;" | 0.05 |
− | | | + | | style="text-align: center;" | 13.863 |
− | | | + | | style="text-align: center;" | 37 degrees C |
− | | | + | | style="text-align: center;" | <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> |
|- | |- | ||
− | | | + | | style="text-align: center;" | 59 |
− | | | + | | style="text-align: center;" | ex5-HPETE |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 60 |
− | | | + | | style="text-align: center;" | ex15-HETE |
− | | | + | | style="text-align: center;" | 21 |
− | | | + | | style="text-align: center;" | 0.0331 |
− | | | + | | style="text-align: center;" | Study in R15L Cells |
− | | | + | | style="text-align: center;" | <ref name="Cong2009”>[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730384/ 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.]</ref> |
|- | |- | ||
− | | | + | | style="text-align: center;" | 61 |
− | |ex15- | + | | style="text-align: center;" | ex15-HPETE |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
− | | | + | | style="text-align: center;" | |
|- | |- | ||
− | | | + | | style="text-align: center;" | 62 |
− | + | | style="text-align: center;" | ex12-HETE | |
− | | | + | | style="text-align: center;" | 180 |
− | | | + | | style="text-align: center;" | 0.004 |
− | + | | style="text-align: center;" | "During the first 2 min., the half-life of 12-HETE was 0.9 s, which implies | |
− | | | ||
− | |- | ||
− | | | ||
− | | | ||
− | | | ||
− | | | ||
− | |"During the first 2 min., the half-life of 12-HETE was 0.9 s, which implies | ||
a fast clearance of the compound from the circulation. However, during | a fast clearance of the compound from the circulation. However, during | ||
the subsequent half-hour the estimated half-life was 3 min. and increased | the subsequent half-hour the estimated half-life was 3 min. and increased | ||
dramatically at the interval of time from 30 to 60 min. (t1/2 around 3 h)." | dramatically at the interval of time from 30 to 60 min. (t1/2 around 3 h)." | ||
− | |<ref name="Dadaian1998”>[http://www.ncbi.nlm.nih.gov/pubmed/9661215 Dadaian M., "12-hydroxyeicosatetraenoic acid is a long-lived substance in the rabbit circulation." Prostaglandins Other Lipid Mediat. 1998 Jan;55(1):3-25. | + | | style="text-align: center;" |<ref name="Dadaian1998”>[http://www.ncbi.nlm.nih.gov/pubmed/9661215 Dadaian M., "12-hydroxyeicosatetraenoic acid is a long-lived substance in the rabbit circulation." Prostaglandins Other Lipid Mediat. 1998 Jan;55(1):3-25.]</ref> |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | | | + | | style="text-align: center;" | 63 |
− | | | + | | style="text-align: center;" | ex12-HPETE |
− | | | + | | style="text-align: center;" | 0.5 |
− | | | + | | style="text-align: center;" | 1.386 |
− | | | + | | style="text-align: center;" | |
− | |<ref name=" | + | | style="text-align: center;" | <ref name="Maclouf1982”>[http://www.pnas.org/content/79/19/6042.abstract J. Maclouf, "Stimulation of leukotriene biosynthesis in human blood leukocytes by platelet-derived 12-hydroperoxy-icosatetraenoic acid" (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 6042-6046 ]</ref> |
|- | |- | ||
+ | | style="text-align: center;" | 64 | ||
+ | | style="text-align: center;" | exAA | ||
+ | | style="text-align: center;" | 240 to 660 | ||
+ | | style="text-align: center;" | 0.003 to 0.001 | ||
+ | | style="text-align: center;" | | ||
+ | | style="text-align: center;" |<ref name="Vinge1985”>[http://www.ncbi.nlm.nih.gov/pubmed/3921386 Vinge E., "Arachidonic acid-induced platelet aggregation and prostanoid formation in whole blood in relation to plasma concentration of indomethacin." Eur J Clin Pharmacol. 1985;28(2):163-9.]</ref> | ||
|} | |} | ||
Revision as of 16:39, 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.
Pseudo-first order reactions.
Reaction # | Species | Half Life (min) | Rate constant(min -1) | Notes | Reference |
---|---|---|---|---|---|
44 | exPGF2a | 528 ± 204 | 0.001 ± 0.003 | Study performed in decidual stromal cells and macrophages in culture. | [1] |
45 | exTXB2 | 20 to 30 | 0.035 to 0.023 | 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 | 0.333 | 2.079 | 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 | 0.231 | 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 | 0.7 | 0.990 | [2] | |
49 | exPGE2 | 900,± 492 | 0.001 ± 0.001 | Study performed in decidual stromal cells and macrophages in culture. | [1] |
50 | ex15-DEOXY-PGJ2 | 720 | 0.001 | 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 | 0.462 to 0.433 | Human brain | [4] |
53 | exPGH2 | 5 | 0.139 | Quoted on supplier page (http://www.enzolifesciences.com/BML-PH002/prostaglandin-h2/) | |
54 | ex5-OXO-ETE | 11 | 0.064 | Study in R15L Cells | [5] |
55 | ex5-HETE | ||||
56 | exLTB4 | 0.47 ± 0.02 to 0.63 ± 0.04 | 1.475 ± 34.657 to 1.100 ± 17.329 | Rabbit, Immunoreactive LTB4 | [6] |
57 | exLTC4 | ||||
58 | exLTA4 | 0.05 | 13.863 | 37 degrees C | [7] |
59 | ex5-HPETE | ||||
60 | ex15-HETE | 21 | 0.0331 | Study in R15L Cells | [5] |
61 | ex15-HPETE | ||||
62 | ex12-HETE | 180 | 0.004 | "During the first 2 min., the half-life of 12-HETE was 0.9 s, which implies
a fast clearance of the compound from the circulation. However, during the subsequent half-hour the estimated half-life was 3 min. and increased dramatically at the interval of time from 30 to 60 min. (t1/2 around 3 h)." |
[8] |
63 | ex12-HPETE | 0.5 | 1.386 | [9] | |
64 | exAA | 240 to 660 | 0.003 to 0.001 | [10] |
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.
- ↑ Dadaian M., "12-hydroxyeicosatetraenoic acid is a long-lived substance in the rabbit circulation." Prostaglandins Other Lipid Mediat. 1998 Jan;55(1):3-25.
- ↑ J. Maclouf, "Stimulation of leukotriene biosynthesis in human blood leukocytes by platelet-derived 12-hydroperoxy-icosatetraenoic acid" (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 6042-6046
- ↑ Vinge E., "Arachidonic acid-induced platelet aggregation and prostanoid formation in whole blood in relation to plasma concentration of indomethacin." Eur J Clin Pharmacol. 1985;28(2):163-9.