COMPARISON OF SUBSTRATE AND INHIBITOR SPECIFICITY OF ARGINASE AND NITRIC-OXIDE (NO) SYNTHASE FOR ARGININE ANALOGS AND RELATED-COMPOUNDS IN MURINE AND RAT MACROPHAGES
COMPARISON OF SUBSTRATE AND INHIBITOR SPECIFICITY OF ARGINASE AND NITRIC-OXIDE (NO) SYNTHASE FOR ARGININE ANALOGS AND RELATED-COMPOUNDS IN MURINE AND RAT MACROPHAGES
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DOI：
10.1006/bbrc.1994.1029
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发表时间：
1994-01-14
影响因子：
3.1
通讯作者：
TEMESI, A
中科院分区：
文献类型：
--
作者：
HRABAK, A;BAJOR, T;TEMESI, A
巨噬细胞中的精氨酸利用酶对作为底物和抑制剂的各种精氨酸类似物和衍生物表现出不同的特异性。分离的精氨酸酶被L-刀豆氨酸(Can)和L-鸟氨酸(Orn)强烈抑制，但被L-高精氨酸(Hom)和L-精氨酸酰胺(ArgNH2)轻微抑制。当在长期细胞培养物中测量释放的尿素时，没有或仅微弱地观察到这些效应。另一方面，L-刀豆氨酸和L-精氨酸酰胺都是长期培养中精氨酸酶的底物。已知的抑制剂或NO合酶无效。 L-刀豆氨酸和L-鸟氨酸的抑制机制不同，但无法确定明确的机制）。 NO合酶仅在未经纯化的长期细胞培养物中进行研究。某些 N-胍基 (NG) 取代的精氨酸衍生物引起显着的抑制作用，而精氨酸酶抑制剂仅具有轻微的作用或没有作用。 L-高精氨酸也被发现是NO合酶的底物。精氨酸类似物和衍生物的这些作用的比较使得计算机辅助近似将这些酶的活性中心与其底物的拟合成为可能。
Arginine utilizing enzymes in macrophages showed different specificities for various arginine analogues and derivatives as substrates and inhibitors. Isolated arginase was strongly inhibited by L-canavanine(Can) and L-ornithine(Orn) but only slightly by L-homoarginine(Hom) and L-argininamide(ArgNH2). These effects were not or only weakly observed when released urea was measured in long term cell cultures. On the other hand, both L-canavanine and L-argininamide were substrates for arginase in long-term cultures. The known inhibitors or NO synthase were ineffective. The mechanisms of inhibition were different for L-canavanine and L-ornithine, but clear mechanisms could not be identified). NO synthase was studied only in long term cell cultures without purification. Certain N-guanidino (NG)-substituted arginine derivatives caused a marked inhibition while inhibitors of arginase had only slight or no effect. L-homoarginine was also found to be the substrate of NO synthase.The comparison of these effects of arginine analogues and derivatives made possible a computer-aided approximation for the fitting of active centers of these enzymes to their substrates.