Transformation of LTA4 to LTC4

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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]


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. [5]
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 [6]
49 exPGE2 900,± 492 0.001 ± 0.001 Study performed in decidual stromal cells and macrophages in culture. [5]
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). [7]
51 exPGJ2
52 exPGD2 1.5 - 1.6 0.462 to 0.433 Human brain [8]
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 [9]
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 [10]
57 exLTC4
58 exLTA4 0.05 13.863 37 degrees C [11]
59 ex5-HPETE
60 ex15-HETE 21 0.0331 Study in R15L Cells [9]
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)."

[12]
63 ex12-HPETE 0.5 1.386 [13]
64 exAA 240 to 660 0.003 to 0.001 [14]

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
  5. ↑ 5.0 5.1 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.
  6. ↑ Cawello W., "Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects." Eur J Clin Pharmacol. 1994;46(3):275-7.
  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.
  8. ↑ Suzuki F., "Transport of prostaglandin D2 into brain." Brain Res. 1986 Oct 22;385(2):321-8.
  9. ↑ 9.0 9.1 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.
  10. ↑ 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.
  11. ↑ 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.
  12. ↑ Dadaian M., "12-hydroxyeicosatetraenoic acid is a long-lived substance in the rabbit circulation." Prostaglandins Other Lipid Mediat. 1998 Jan;55(1):3-25.
  13. ↑ 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
  14. ↑ 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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