Difference between revisions of "Transformation of LTA4 to LTC4"

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== Related Reactions ==
 
== Related Reactions ==
 +
 +
 +
{| 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
 +
| 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
 +
| style="text-align: center;" |
 +
| 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.
 +
| 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).
 +
| 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;" |
 +
| style="text-align: center;" |
 +
|-
 +
| 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
 +
| 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;" |
 +
|-
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| 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
 +
| 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;" |
 +
| style="text-align: center;" |
 +
|-
 +
| 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;" | "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)."
 +
| 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;" | 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 16:31, 5 September 2016

Return to overview

To generate LTC4, a supramolecular complex of 5-LOX, FLAP and leukotriene C4 synthase is formed on the nuclear membrane due to the increase of intracellular calcium \cite{Woods1993, Hammarberg2000, Radmark2015, Evans2008, Mandal2004, Mandal2008}

Reaction

Chemical equation

AA \rightleftharpoons PGH2

Rate equation

Parameters

Michaelis-Menten Constants
Value Units Species Notes Reference
0.3 �± 0.06 mM Human Expression Vector: E. Coli.

Enzyme: Wild Type hLTC4S pH:7.8 Temperature:20 °C

[1]
3.00E-02 ± 1.00E-02 mM Human Expression Vector: E Coli

Enzyme: Wild type LTC4S pH: 7.8 Temperature: 37 °C

[2]
Enzyme Turnover Numbers
Value Units Species Notes Reference
702 per minute Human Expression Vector: E. Coli.

Enzyme: Wild Type hLTC4S pH:7.8 Temperature:20 °C

[1]
1560 ± 240 per minute Human Expression Vector: E Coli

Enzyme: Wild type LTC4S pH: 7.8 Temperature: 37 °C

[2]
LTC4S Abundance
Value Units Species Notes Reference
26.8 ppm Human Expression Vector: Lung

Enzyme: LTC4S pH: 7.5 Temperature: 37 °C

[3]
33.0 ppm Human Expression Vector: Esophagus

Enzyme: LTC4S pH: 7.5 Temperature: 37 °C

[3]
13.9 ppm Human Expression Vector: Adrenal Gland

Enzyme: LTC4S pH: 7.5 Temperature: 37 °C

[3]
Gibbs Free Energy Change
Value Units Species Notes Reference
9.934128 kcal/mol Not stated Estimated

Enzyme: LTC4S Substrate: LTA4 Product: LTC4 pH: 7.3 ionic strength: 0.25

[4]

References

  1. ↑ 1.0 1.1 [http://www.jbc.org/content/285/52/40771.full.pdf Rinaldo A. " Arginine 104 Is a Key Catalytic Residue in Leukotriene C4 Synthase J Biochem 2010, 285, 40771-40776]
  2. ↑ 2.0 2.1 [http://www.jbc.org/content/early/2013/12/23/jbc.M113.534628 Niegowski D. " Crystal structures of Leukotriene C4 synthase in complex with product analogs, implications for the enzyme mechanism J. Biol. Chem. 289, 5199-5207 (2014)] Cite error: Invalid <ref> tag; name "Niegowski2013" defined multiple times with different content
  3. ↑ 3.0 3.1 3.2 M. Kim A draft map of the human proteome Nature, 2014 509, 575–581
  4. ↑ Caspi et al 2014, "The MetaCyc database of metabolic pathways and enzymes and the BioCyc collection of Pathway/Genome Databases," Nucleic Acids Research 42:D459-D471

Related 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
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
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 [4]
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 [5]
57 exLTC4
58 exLTA4 0.05 13.863 37 degrees C [6]
59 ex5-HPETE
60 ex15-HETE 21 0.0331 Study in R15L Cells [4]
61 ex15-HPETE
62 ex12-HETE 180 0.004
63 ex12-HPETE 0.5 1.386 "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)."

[7]
64 exAA 240 to 660 0.003 to 0.001 [8]
  1. ↑ 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.
  2. ↑ Cawello W., "Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects." Eur J Clin Pharmacol. 1994;46(3):275-7.
  3. ↑ F. Fitzpatrick, "Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro." J Biol Chem. 1983 Oct 10;258(19):11713-8.
  4. ↑ 4.0 4.1 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ Dadaian M., "12-hydroxyeicosatetraenoic acid is a long-lived substance in the rabbit circulation." Prostaglandins Other Lipid Mediat. 1998 Jan;55(1):3-25.
  8. ↑ 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.
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