TAILIEUCHUNG - Báo cáo khoa học: Structure, biochemistry and biology of hepoxilins An update

Hepoxilins are biologically relevant epoxy-hydroxy eicosanoids synthesized through the 12S-lipoxygenase (12S-LOX) pathway of the arachidonic acid (AA) metabolism. The pathway is bifurcated at the level of 12S-hydro-peroxy-eicosatetraenoic acid (12S-HpETE), which can either be reduced to 12S-hydro-eicosatetraenoic acid (12S-HETE) or converted to hepoxilins. | ỊFEBS Journal MINIREVIEW Structure biochemistry and biology of hepoxilins An update Santosh Nigam Maria-Patapia Zafiriou Rupal Deva Roberto Ciccoli and Renate Roux-Van der Merwe Eicosanoid Lipid Research Division and Centre for ExperimentalGynecology Breast Research Charites - University MedicalCentre Benjamin Franklin Berlin Germany Keywords glutathione peroxidases hepoxilin A3 hepoxilin A3 synthase insulin secretion IRE1 a lung fibrosis RINm5F cells Correspondence S. Nigam Eicosanoid Lipid Research Division and Centre for Experimental Gynecology Breast Research Charites -University MedicalCentre Benjamin Franklin D-12200 Berlin Germany Fax Tel 49 30 8445 2467 E-mail Present address Department of Food Technology Tschwane University of Technology Pretoria South Africa Received 12 Janurary 2007 revised 30 April 2007 accepted 29 May 2007 doi Hepoxilins are biologically relevant epoxy-hydroxy eicosanoids synthesized through the 12S-lipoxygenase 12S-LOX pathway of the arachidonic acid AA metabolism. The pathway is bifurcated at the level of 12S-hydro-peroxy-eicosatetraenoic acid . which can either be reduced to 12S-hydro-eicosatetraenoic acid 12S-HETE or converted to hepoxilins. The present review gives an update on the biochemistry biology and clinical aspects of hepoxilin-based drug development. The isolation cloning and characterization of a rat leukocyte-type 12S-LOX from rat insulinoma RINm5F cells revealed a 12S-LOX possessing an intrinsic 8S R-hydroxy-11 12-epoxyeicosa-5Z 9E 14Z-trienoic acid HXA3 synthase activity. Site-directed mutagenesis studies on rat 12S-LOX showed that the HXA3 synthase activity was impaired when the positional specificity of AA was altered. Interestingly amino acid Leu353 and not conventional sequence determinants Met419 and Ile418 was found to be a crucial sequence determinant for AA oxygenation. The regulation of HXA3 formation is dependent on the cellular overall .

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