Leukotriene C4 synthase

Tornhamre S, Schmidt TJ, Nasman-Glaser B, Ericsson I, Ake L. Inhibitory effects of helenalin and related compounds on 5-lipoxygenase and leukotriene C4 synthase in human blood cells. Biochem Pharmacol 2001 62 903-911. 

Leukotrienes (LTA, LTB LTC, LTD, and LTE ) are synthesized from arachi-donic acid by a cascade of enzymes that include 5-lipoxygenase (5-LOX), 5-lipoxy-genase-activating protein (FLAP), and leukotriene C4 synthase (LTC synthase) (79,80). The leukotriene LTA is synthesized by 5-LOX in the first step and is an unstable precursor that is then enzymatically converted to LTB or LTC (80,81), which can subsequently be metabolized to LTD and LTE. LTC, LTD, and LTE are the components of the slow-reacting substance of anaphylaxis. These moieties, particularly LTC and LTD, are active forms of CysLTs that interact with the G protein-coupled cysteinyl leukotriene receptors (CysLtrl and CysLtr2) (70,81,82). Once engaged, the activated CysLtrs receptors stimulate the secretion of mucus and induce edema and bronchoconstriction (81). 

Currie GP, Lima JJ, Sylvester JE, Lee DK, Cockburn WJ, Lipworth BJ. (2003) Leukotriene C4 synthase polymorphisms and responsiveness to leukotriene antagonists in asthma. Br J Clin Pharmacol. 56, 422-426. 

Isidoro-Garcia M, Davila 1, Moreno E, Lorente F, Gonzalez-Sarmiento R. (2005) Analysis of the leukotriene C4 synthase A-444C promoter polymorphism in a Spanish population. J... 

Kawagishi Y, Mita H, Taniguchi M, et al. (2002) Leukotriene C4 synthase promoter polymorphism in Japanese patients with aspirin-induced asthma. J Allergy Clin Immunol. 109,936-942. 

Sanak M, Simon HU, Szczeklik A. (1997) Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet. 350, 1599-1600. 

Van SR, Stevenson DD, Baldasaro M, et al. (2000) 5 Flanking region polymorphism of the gene encoding leukotriene C4 synthase does not correlate with the aspirin-intolerant asthma phenotype in the United States. J Allergy Clin Immunol. 106(1 pt. 1), 72-76. 

Sampson AP, Cowbum AS, Sladek K, et al. (1997) Profound overexpression of leukotriene C4 synthase in bronchial biopsies from aspirin-intolerant asthmatic patients. Int Arch Allergy Immunol. 113, 355-357. 

LEUKOTRIENE C4 SYNTHASE LEUKOTRIENE C4 SYNTHASE GLUTATHIONE S-TRANSFERASE LEVANASE Levans,... 

Murakami M, Austen KF, Bingham CO 3rd, Friend DS, Penrose JF, Arm JP (1995) Interleukin-3 regulates development of the 5-lipoxygenase/leukotriene C4 synthase pathway in mouse mast cells. J Biol Chem 270 22653-22656... 

Sayers I, Barton S, Rorke S, et al Allelic association and functional studies of promoter poly-moiphism in the leukotriene C4 synthase gene (LTC4S) in asthma. Thorax 2003 58 417 -424. (NC)... 

Asano K, Shiomi T, Hasegaw a N, et al Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT( l) antagonist, pranlukast, in Japanese patients with moderate asthma. Pharmacogenetics 2002 12 565-570. (Ila)... 

The GST responsible for leukotriene C4 synthase activity has recently been purified (N2, N3) and it is now certain that the reaction is catalyzed by a unique membrane-bound enzyme that is distinct from the microsomal GST characterized by Morgenstem and his colleagues (S29, S30). 

In addition to the four families of mammalian cytosolic GST, membrane-bound forms of the enzyme exist. Amino acid sequencing and cDNA cloning have demonstrated that the A -ethylmaleimide-activatable microsomal GST shares no homology with the cytosolic enzymes (D3) and therefore appears to be an example of convergent evolution. Recent evidence suggests that leukotriene C4 synthase... 

The molecular cloning of rat and human microsomal GST, described by DeJong et al. (D3), has demonstrated the absence of homology between these enzymes and the cytosolic GST. Although it is clear that microsomal GST and the membrane-bound leukotriene C4 synthase are distinct enzymes (A14, N2, S29), their exact molecular relationship is at present unclear it is unlikely that they are members of the same gene family (N3). 

N2. Nicholson, D. W., Ali, A., Klemba, M. W., Munday, N. A., Zamboni, R. J., and Ford-Hutchinson, A. W., Human leukotriene C4 synthase expression in dimethyl sulfoxide-differentiated U937 cells. J. Biol Chem. 267, 17849-17857 (1992). 

Soderstrdm, M., Hammarstrom, S., and Mannervik, B., Leukotriene C4 synthase in mouse, mastocytoma cells. An enzyme distinct from cytosolic and microsomal glutathione transferases. Biochem. J. 250, 713-718 (1988). 

Lam BK, Austen KF. Leukotriene C4 synthase a pivotal enzyme in cellular biosynthesis of the cysteinyl leukotrienes. Prostaglandins Other Lipid Mediat. 2002 68—69 511 520. 

Skin Genetic determinants of aspirin-induced urticaria and aspirin-intolerant chronic urticaria have been identified. Two tumor necrosis factor a (TNF-a) promoter poljnnoiphisms and a leukotriene C4 synthase promoter polymorphism are associated with aspirin-induced urticaria [65, 66 ]. A transforming growth factor P-1 (TGFpi) promoter polymorphism is associated with aspirin-intolerant chronic urticaria [67 ]. 

Sanchez-Borges M, Acevedo N, Vergara C, Jimenez S, Zabner-Oziel P, Monzon A, Caraballo L. The A-444C polymorphism in the leukotriene C4 synthase gene is associated with aspirin-induced urticaria. J Investig Allergol Clin Immunol 2009 19(5) 375-82. 

Nicholson DW, Ali A, Vaillancourt JP, Calaycay JR, Mumford RA, Zamboni RJ, Ford-Hutchinson A. Purification to homogeneity and the N-terminal sequence of human leukotriene C4 synthase a homodimeric glutathione S-transferase composed of 18-kDa subunits. Proc Natl Acad Sci USA 1993 90 2015-2119. 

Welsch DJ, Creely DP, Hauser SD, Methis KJ, Krivi GG, Isakson PC. Molecular cloning and expression of human leukotriene C4 synthase. Proc Natl Acad Sci USA 1994 91 9745-9749. 

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