MACROPHAGE CYTOTOXICITY - ROLE FOR L-ARGININE DEIMINASE AND IMINO-NITROGEN OXIDATION TO NITRITE
MACROPHAGE CYTOTOXICITY - ROLE FOR L-ARGININE DEIMINASE AND IMINO-NITROGEN OXIDATION TO NITRITE
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DOI：
10.1126/science.2432665
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发表时间：
1987-01-23
期刊：
影响因子：
56.9
通讯作者：
VAVRIN, Z
中科院分区：
文献类型：
--
作者：
HIBBS, JB;TAINTOR, RR;VAVRIN, Z
以前的研究表明，细胞毒性激活的巨噬细胞会抑制肿瘤靶细胞的DNA合成、线粒体呼吸和乌头酸酶活性。L依赖精氨酸合成L-瓜氨酸和亚硝酸盐的生化途径，再加上一个效应机制，现在被证明导致了这种代谢抑制模式。小鼠细胞毒激活的巨噬细胞在L-精氨酸存在下合成L-瓜氨酸和亚硝酸盐，但不合成D-精氨酸。NG-单甲基-L-精氨酸可抑制细胞毒激活的巨噬细胞合成L-瓜氨酸和亚硝酸盐，从而抑制这一细胞毒效应机制。这种激活的巨噬细胞细胞毒效应系统与L-精氨酸脱氨酶活性有关，L-精氨酸胍基团上的亚氨基被脱亚胺酶反应除去后氧化成亚硝酸根。这种脱亚胺酶的替代底物L-高精氨酸转化为L-高瓜氨酸，同时合成亚硝酸盐和类似的生物效应。
Previous studies have shown that cytotoxic activated macrophages cause inhibition of DNA synthesis, of mitochondrial respiration, and of aconitase activity in tumor target cells. An L-arginine-dependent biochemical pathway synthesizing L-citrulline and nitrite, coupled to an effector mechanism, is now shown to cause this pattern of metabolic inhibiton. Murine cytotoxic activated macrophages synthesize L-citrulline and nitrite in the presence of L-arginine but not D-arginine. L-Citrulline and nitrite biosynthesis by cytotoxic activated macrophages is inhibited by NG-monomethyl-L-arginine, which also inhibits this cytotoxic effector mechanism. This activated macrophage cytotoxic effector system is associated with L-arginine deiminase activity, and the imino nitrogen removed from the guanido group of L-arginine by the deiminase reaction subsequently undergoes oxidation to nitrite. L-Homoarginine, an alternative substrate for this deiminase, is converted to L-homocitrulline with concurrent nitrite synthesis and similar biologic effects.