脂氧素 (LX) 的生物合成
中文名称
通路描述
脂氧素 A4 (LXA4) 和 B4 (LXB4) 是从人类中性粒细胞与 15-羟基二十碳四烯酸 (15-HpETE) 孵育后结构特征化的，每个分子均含有三个羟基和一个共轭四烯。LXA4 的第三个羟基位于 C-6，而 LXB4 位于 C-14。研究表明，花生四烯酸 5-脂氧酶 (ALOX5) 与花生四烯酸 12-脂氧酶 (ALOX12) 或花生四烯酸 15-脂氧酶 (ALOX15) 活性协同作用，通过三种不同的途径产生脂氧素。中性粒细胞 ALOX5 可产生并分泌白细胞介素 A4 (LTA4)，该物质被血小板摄取，随后由 ALOX12 作用形成脂氧素。同样，ALOX15 可生成 15-羟基二十碳四烯酸 (15-HpETE) 或 15-羟基二十碳四烯酸 (15-HETE)，后者可被单核细胞和中性粒细胞摄取，其中高表达的 ALOX5 利用其生成脂氧素。最后，阿司匹林乙酰化前列腺素 G/H 合酶 2 (PTGS2)，使其无法合成前列腺素，可作为 15-脂氧酶。这导致形成 15R-HETE，最终产生具有 C-15 羟基不同立体化学但具有相似生物活性的 epi-脂氧素 (Chiang et al. 2006, Buczynski et al. 2009, Vance & Vance 2008, Stsiapanava et al. 2017)。
英文描述
Biosynthesis of Lipoxins (LX) Lipoxins A4 (LXA4) and B4 (LXB4), structurally characterized from human neutrophils incubated with 15-hydroperoxy-eicosatetraenoic acid (15-HpETE), each contain three hydroxyl moieties and a conjugated tetraene. The third hydroxyl of LXA4 is positioned at C-6, and of LXB4 at C-14. The action of arachidonate 5-lipoxygenase (ALOX5), in concert with an arachidonate 12-lipoxygenase (ALOX12) or arachidonate 15-lipoxygenase (ALOX15) activity, has been shown to produce lipoxins by three distinct pathways. Neutrophil ALOX5 can produce and secrete leukotriene A4 (LTA4) that is taken up by platelets, where it is acted upon by ALOX12 to form lipoxins. Likewise, ALOX15s can generate either 15-hydroperoxy-eicosatetraenoic acid (15-HpETE) or 15-hydro-eicosatetraenoic acid (15-HETE) that can be taken up by monocytes and neutrophils, where highly expressed ALOX5 uses it to generate lipoxins. Finally, aspirin acetylated prostaglandin G/H synthase 2 (PTGS2), rendered unable to synthesize prostaglandins, can act as a 15-lipoxygenase. This leads to the formation of 15R-HETE and culminates in creation of epi-lipoxins, which have altered stereochemistry at the C-15 hydroxyl but similar biological potency (Chiang et al. 2006, Buczynski et al. 2009, Vance & Vance 2008, Stsiapanava et al. 2017).
所含基因
6 个基因