Difference between revisions of "Degradation Pathways"

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{| class="wikitable"
 
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! style="text-align: center; font-weight: bold;" | Reaction #
 
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! style="text-align: center; font-weight: bold;" | Species
 
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! style="text-align: center; font-weight: bold;" | Half Life (min)
 
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! style="text-align: center; font-weight: bold;" | Rate constant(min -1)
 
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! style="text-align: center; font-weight: bold;" | Notes
 
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! style="text-align: center; font-weight: bold;" | Reference
 
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| style="text-align: center;" | 44
 
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| style="text-align: center;" | exPGF2a
 
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| style="text-align: center;" | 900 ± 492
 
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| style="text-align: center;" | 0.001 ± 0.001
 
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| style="text-align: center;" |Study performed in decidual stromal cells and macrophages in culture.
 
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| 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>
 
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| style="text-align: center;" | 45
 
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| style="text-align: center;" | exTXB2
 
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| style="text-align: center;" | 20 to 30
 
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| style="text-align: center;" | 0.035 to 0.023
 
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| 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.
 
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| style="text-align: center;" |
 
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| style="text-align: center;" | 46
 
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| style="text-align: center;" | exTXA2
 
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| style="text-align: center;" | 0.333
 
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| style="text-align: center;" | 2.079
 
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| 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.
 
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| style="text-align: center;" |
 
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| style="text-align: center;" | 47
 
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| style="text-align: center;" | ex6-KETO-PGF1A
 
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| style="text-align: center;" | 30
 
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| style="text-align: center;" | 0.0231
 
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| style="text-align: center;" | Human Plasma
 
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| style="text-align: center;" | <ref name="Ylikorkala1981”>[https://www.ncbi.nlm.nih.gov/pubmed/7025068 Ylikorkala, "Measurement of 6-keto-prostaglandin E1 alpha in human plasma with radioimmunoassay: effect of prostacyclin infusion." Prostaglandins Med. 1981 Apr;6(4):427-36.]</ref>
 
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| style="text-align: center;" | 48
 
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| style="text-align: center;" | exPGI2
 
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| style="text-align: center;" | 3
 
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| style="text-align: center;" | 0.231
 
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| style="text-align: center;" |
 
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| 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>
 
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| style="text-align: center;" | 49
 
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| style="text-align: center;" | exPGE2
 
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| style="text-align: center;" | 528 ±  204
 
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| style="text-align: center;" | 0.001 ± 0.003
 
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| style="text-align: center;" | Study performed in decidual stromal cells and macrophages in culture.
 
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| 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>
 
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| style="text-align: center;" | 50
 
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| style="text-align: center;" | ex15-DEOXY-PGJ2
 
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| style="text-align: center;" | 720
 
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| style="text-align: center;" | 0.001
 
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| 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).
 
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| 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>
 
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| style="text-align: center;" | 51
 
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| style="text-align: center;" | exPGJ2
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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|-
 
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| rowspan="2" style="text-align: center;" | 52
 
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| rowspan="2" style="text-align: center;" | exPGD2
 
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| style="text-align: center;" | 1.5 - 1.6
 
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| style="text-align: center;" | 0.462 to 0.433
 
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| style="text-align: center;" | Human brain
 
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| style="text-align: center;" | <ref name="Suzuki1986”>[https://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>
 
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| style="text-align: center;" | 30
 
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| style="text-align: center;" | 0.023
 
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| style="text-align: center;" | Human plasma
 
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| style="text-align: center;" | <ref name="Schuligoi2007”>[http://www.sciencedirect.com/science/article/pii/S0006295207001918?via%3Dihub R. Schuligoi. "PGD2 metabolism in plasma: Kinetics and relationship with bioactivity on DP1 and CRTH2 receptors" Biochemical Pharmacology, Volume 74, Issue 1, 30 June 2007, Pages 107-117]</ref>
 
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| style="text-align: center;" | 53
 
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| style="text-align: center;" | exPGH2
 
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| style="text-align: center;" | 5
 
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| style="text-align: center;" | 0.139
 
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| style="text-align: center;" | Quoted on supplier page (http://www.enzolifesciences.com/BML-PH002/prostaglandin-h2/)
 
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| style="text-align: center;" | 54
 
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| style="text-align: center;" | ex5-OXO-ETE
 
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| style="text-align: center;" | 11
 
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| style="text-align: center;" | 0.064
 
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| style="text-align: center;" | Study half life of 15-OXO-ETE in in R15L Cells
 
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| 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>
 
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| style="text-align: center;" | 55
 
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| style="text-align: center;" | ex5-HETE
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" | 56
 
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| style="text-align: center;" | exLTB4
 
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| style="text-align: center;" | 0.47 ± 0.02 to 0.63 ± 0.04
 
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| style="text-align: center;" | 1.475 ± 34.657 to 1.100 ± 17.329
 
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| style="text-align: center;" | Rabbit, Immunoreactive LTB4
 
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| 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>
 
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| style="text-align: center;" | 57
 
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| style="text-align: center;" | exLTC4
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" | 58
 
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| style="text-align: center;" | exLTA4
 
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| style="text-align: center;" | 0.05
 
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| style="text-align: center;" | 13.863
 
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| style="text-align: center;" | 37 degrees C
 
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| 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>
 
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| style="text-align: center;" | 59
 
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| style="text-align: center;" | ex5-HPETE
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" | 60
 
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| style="text-align: center;" | ex15-HETE
 
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| style="text-align: center;" | 21
 
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| style="text-align: center;" | 0.0331
 
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| style="text-align: center;" | Study in R15L Cells
 
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| 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>
 
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| style="text-align: center;" | 61
 
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| style="text-align: center;" | ex15-HPETE
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" |
 
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| style="text-align: center;" | 62
 
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| style="text-align: center;" | ex12-HETE
 
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| style="text-align: center;" | 180
 
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| style="text-align: center;" | 0.004
 
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| style="text-align: center;" | "During the first 2 min., the half-life of 12-HETE was 0.9 s, which implies
 
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a fast clearance of the compound from the circulation. However, during
 
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the subsequent half-hour the estimated half-life was 3 min. and increased
 
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dramatically at the interval of time from 30 to 60 min. (t1/2 around 3 h)."
 
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| 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>
 
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| style="text-align: center;" | 63
 
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| style="text-align: center;" | ex12-HPETE
 
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| style="text-align: center;" | 0.5
 
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| style="text-align: center;" | 1.386
 
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| style="text-align: center;" |
 
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| 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>
 
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| style="text-align: center;" | 64
 
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| style="text-align: center;" | exAA
 
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| style="text-align: center;" | 240 to 660
 
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| style="text-align: center;" | 0.003 to 0.001
 
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| style="text-align: center;" |
 
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| 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>
 
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== References ==
 
== References ==
 
<references/>
 
<references/>

Revision as of 14:50, 16 May 2019

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.

Pseudo-first order reactions. k = ln(2)/t(0.5)


References

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