Arachidonate 5-lipoxygenase-activating protein also known as 5-lipoxygenase activating protein, or FLAP, is a protein that in humans is encoded by the ALOX5APgene.[4][5]
Function
FLAP is necessary for the activation of 5-lipoxygenase and therefore for the production of leukotrienes, 5-hydroxyeicosatetraenoic acid, 5-oxo-eicosatetraenoic acid, and specialized pro-resolving mediators of the lipoxin and resolvin classes.[6][7] It is an integral protein within the nuclear membrane. FLAP is necessary in synthesis of leukotriene, which are lipid mediators of inflammation that is involved in respiratory and cardiovascular diseases. FLAP functions as a membrane anchor for 5-lipooxygenase and as an amine acid-bind protein. How FLAP activates 5-lipooxygenase is not completely understood, but there is a physical interaction between the two. [citation needed] FLAP structure consists of 4 transmembrane alpha helices, but they are found in trimer forming a barrel. The barrel is about 60 Å high and 36 Å wide.[8]
Clinical significance
Leukotrienes, which require the FLAP protein to be synthesized, have an established pathological role in allergic and respiratory diseases. Animal and human genetic evidence suggests they may also have an important role in atherosclerosis, myocardial infarction, and stroke.[9] The structure of FLAP provides a tool for the development of novel therapies for respiratory and cardiovascular diseases and for the design of focused experiments to probe the cell biology of FLAP and its role in leukotriene biosynthesis.[8][10]
^Yandava CN, Kennedy BP, Pillari A, Duncan AM, Drazen JM (February 1999). "Cytogenetic and radiation hybrid mapping of human arachidonate 5-lipoxygenase-activating protein (ALOX5AP) to chromosome 13q12". Genomics. 56 (1): 131–3. doi:10.1006/geno.1998.5651. PMID10036194.
^Peters-Golden M, Brock TG (2003). "5-lipoxygenase and FLAP". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 69 (2–3): 99–109. doi:10.1016/S0952-3278(03)00070-X. PMID12895592.
He YL, Zhu M, Jin XP, Zhou YL (November 2009). "[Relationship of polymorphism of SG13S114A/T in ALOX5AP gene with atherosclerotic cerebral infarction]". Zhejiang da Xue Xue Bao. Yi Xue Ban = Journal of Zhejiang University. Medical Sciences. 38 (6): 630–3. doi:10.3785/j.issn.1008-9292.2009.06.013. PMID20014490.
York TP, Vargas-Irwin C, Anderson WH, van den Oord EJ (May 2009). "Asthma pharmacogenetic study using finite mixture models to handle drug-response heterogeneity". Pharmacogenomics. 10 (5): 753–67. doi:10.2217/pgs.09.19. PMID19450127.
Bizzintino JA, Khoo SK, Zhang G, Martin AC, Rueter K, Geelhoed GC, Goldblatt J, Laing IA, Le Souëf PN, Hayden CM (July 2009). "Leukotriene pathway polymorphisms are associated with altered cysteinyl leukotriene production in children with acute asthma". Prostaglandins, Leukotrienes, and Essential Fatty Acids. 81 (1): 9–15. doi:10.1016/j.plefa.2009.05.022. PMID19524426.
van der Net JB, Janssens AC, Defesche JC, Kastelein JJ, Sijbrands EJ, Steyerberg EW (February 2009). "Usefulness of genetic polymorphisms and conventional risk factors to predict coronary heart disease in patients with familial hypercholesterolemia". The American Journal of Cardiology. 103 (3): 375–80. doi:10.1016/j.amjcard.2008.09.093. PMID19166692.
Liu J, Sun K, Bai Y, Zhang W, Wang X, Wang Y, Wang H, Chen J, Song X, Xin Y, Liu Z, Hui R (June 2009). "Association of three-gene interaction among MTHFR, ALOX5AP and NOTCH3 with thrombotic stroke: a multicenter case-control study". Human Genetics. 125 (5–6): 649–56. doi:10.1007/s00439-009-0659-0. PMID19373490. S2CID21475249.
Tsai AK, Li N, Hanson NQ, Tsai MY, Tang W (December 2009). "Associations of genetic polymorphisms of arachidonate 5-lipoxygenase-activating protein with risk of coronary artery disease in a European-American population". Atherosclerosis. 207 (2): 487–91. doi:10.1016/j.atherosclerosis.2009.06.018. PMID19596330.
Steinhilber D (July 1994). "5-Lipoxygenase: enzyme expression and regulation of activity". Pharmaceutica Acta Helvetiae. 69 (1): 3–14. doi:10.1016/0031-6865(94)90024-8. PMID7938075.
Oosterveer DM, Versmissen J, Yazdanpanah M, van der Net JB, Defesche JC, Kastelein JJ, Sijbrands EJ (September 2009). "5-Lipoxygenase activating protein (ALOX5AP) gene variants associate with the presence of xanthomas in familial hypercholesterolemia". Atherosclerosis. 206 (1): 223–7. doi:10.1016/j.atherosclerosis.2009.02.019. PMID19361804.
