Dudek R R, Conforto A, Pinto V, Wildhirt S, Suzuki H
Department of Experimental Cardiology, Huntington Medical Research Institutes, Pasadena, California 91101, USA.
Proc Soc Exp Biol Med. 1995 May;209(1):60-4. doi: 10.3181/00379727-209-43878.
Nitric oxide synthase (NOS) shows similarities to cytochrome P-450 reductase. The two enzymes catalyze the oxidation of N-omega-hydroxy-L-arginine by NADPH and oxygen to nitric oxide (NO) and citrulline. Nitric oxide synthase activity is inhibited by L-arginine analogs like N-omega-nitro-L-arginine, which does not affect cytochrome P-450 reductase. Dihydroergotamine, miconazole, and troleandomycin are classical inhibitors of cytochrome. The present study shows the concentration-dependent inhibitory effect of these compounds and of L- but not D-N-omega-nitro-arginine on the activity of constitutive nitric oxide synthase from bovine aortic endothelial cells. Activity of nitric oxide synthase was estimated by measurement of conversion of [3H]arginine to [3H]citrulline. The tested cytochrome P-450 inhibitors are likely to interfere with heme of nitric oxide synthase. The data confirms a similarity as well as functional differences between the enzymes.
一氧化氮合酶（NOS）与细胞色素P-450还原酶有相似之处。这两种酶催化N-ω-羟基-L-精氨酸在NADPH和氧气作用下氧化生成一氧化氮（NO）和瓜氨酸。一氧化氮合酶活性受到L-精氨酸类似物如N-ω-硝基-L-精氨酸的抑制，而这种类似物并不影响细胞色素P-450还原酶。双氢麦角胺、咪康唑和醋竹桃霉素是细胞色素的经典抑制剂。本研究显示了这些化合物以及L-型而非D-型N-ω-硝基精氨酸对牛主动脉内皮细胞组成型一氧化氮合酶活性的浓度依赖性抑制作用。通过测量[3H]精氨酸向[3H]瓜氨酸的转化来评估一氧化氮合酶的活性。所测试的细胞色素P-450抑制剂可能会干扰一氧化氮合酶的血红素。数据证实了这些酶之间的相似性以及功能差异。
