Discovery of a second 15S-lipoxygenase in humans
Discovery of a second 15S-lipoxygenase in humans
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DOI：
10.1073/pnas.94.12.6148
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发表时间：
1997-06-10
影响因子：
11.1
通讯作者：
Chang, MS
中科院分区：
文献类型：
--
作者：
Brash, AR;Boeglin, WE;Chang, MS
花生四烯酸的脂氧合酶代谢存在于特定的血细胞类型和上皮组织中，并在炎症和组织损伤中被激活。在研究人类皮肤脂氧合酶表达的过程中，我们在某些上皮组织中检测到并鉴定了一种先前未知的至少部分解释花生四烯酸15S脂氧合酶代谢的酶，该基因是从人的发根中克隆的，在前列腺、肺和角膜中也检测到了该基因的表达；另外16种人类组织，包括外周血白细胞，都没有表达该基因。该基因编码676个氨基酸，计算相对分子质量为76 kDa，氨基酸序列与已知的人类55-，12S-酸性15S-脂氧合酶的同源性约为40%。当在HEK 293细胞中表达时，新发现的酶只将花生四烯酸转化为15S-过氧二十碳四烯酸，而亚油酸的代谢较差，这些特征与先前报道的15S-脂氧合酶形成对比，15S-脂氧合酶主要在C-15氧化花生四烯酸，但也有部分在C-12氧化花生四烯酸，亚油酸是一个很好的底物。不同的催化活性和组织分布表明，与先前报道的人类15S脂氧合酶相比，新酶具有不同的功能。
The lipoxygenase metabolism of arachidonic acid occurs in specific blood cell types and epithelial tissues and is activated in inflammation and tissue injury, In the course of studying lipoxygenase expression in human skin, we detected and characterized a previously unrecognized enzyme that at least partly accounts for the 15S-lipoxygenase metabolism of arachidonic acid in certain epithelial tissues, The cDNA was cloned from human hair roots, and expression of the mRNA was detected also in prostate, lung, and cornea; an additional 16 human tissues, including peripheral blood leukocytes, were negative for the mRNA. The cDNA encodes a protein of 676 amino acids with a calculated molecular mass of 76 kDa, The amino acid sequence has approximately 40% identity to the known human 55-, 12S-, acid 15S-lipoxygenases, When expressed in HEK 293 cells, the newly discovered enzyme converts arachidonic acid exclusively to 15S-hydroperoxeicosatetraenoic acid, while linoleic acid is less well metabolized, These features contrast with the previously reported 15S-lipoxygenase, which oxygenates arachidonic acid mainly at C-15, but also partly at C-12, and for which linoleic acid is an excellent substrate. The different catalytic activities and tissue distribution suggest a distinct function for the new enzyme compared with the previously reported human 15S-lipoxygenase.