Knowles R G, Palacios M, Palmer R M, Moncada S
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Proc Natl Acad Sci U S A. 1989 Jul;86(13):5159-62. doi: 10.1073/pnas.86.13.5159.
A soluble enzyme obtained from rat forebrain catalyzes the NADPH-dependent formation of nitric oxide (NO) and citrulline from L-arginine. The NO formed stimulates the soluble guanylate cyclase and this stimulation is abolished by low concentrations of hemoglobin. The synthesis of NO and citrulline is dependent on the presence of physiological concentrations of free Ca2+ and is inhibited by NG-monomethyl-L-arginine, but not by its enantiomer NG-monomethyl-D-arginine or by L-canavanine. L-Homoarginine, L-arginyl-L-aspartate, or L-arginine methyl ester can replace L-arginine as substrates for the enzyme. These results indicate that NO is formed from L-arginine in the brain through an enzymic reaction similar to that in vascular endothelial cells, neutrophils, and macrophages, adding support to our hypothesis that the formation of NO from L-arginine is a widespread transduction mechanism for the stimulation of the soluble guanylate cyclase.
从大鼠前脑获得的一种可溶性酶催化L - 精氨酸依赖NADPH生成一氧化氮（NO）和瓜氨酸。生成的NO刺激可溶性鸟苷酸环化酶，低浓度血红蛋白可消除这种刺激。NO和瓜氨酸的合成依赖于生理浓度游离Ca2+的存在，且受NG - 单甲基 - L - 精氨酸抑制，但不受其对映体NG - 单甲基 - D - 精氨酸或L - 刀豆氨酸抑制。L - 高精氨酸、L - 精氨酰 - L - 天冬氨酸或L - 精氨酸甲酯可替代L - 精氨酸作为该酶的底物。这些结果表明，大脑中NO由L - 精氨酸通过类似于血管内皮细胞、中性粒细胞和巨噬细胞中的酶促反应生成，这为我们的假说提供了支持，即L - 精氨酸生成NO是刺激可溶性鸟苷酸环化酶的一种广泛的转导机制。
