Boucher J L, Custot J, Vadon S, Delaforge M, Lepoivre M, Tenu J P, Yapo A, Mansuy D
Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, Université Paris V, CNRS URA 400, France.
Biochem Biophys Res Commun. 1994 Sep 30;203(3):1614-21. doi: 10.1006/bbrc.1994.2371.
N omega-Hydroxy-L-arginine (L-NOHA) is a potent inhibitor of the hydrolysis of L-arginine (L-Arg) to L-ornithine (L-Orn) catalyzed by purified bovine liver arginase (BLA). It appears as one of the most powerful arginase inhibitors reported so far (Ki = 150 microM). The other products of NO synthase are either without effect (NO2-, NO3-) or much weaker inhibitors (L-citrulline (L-Cit) and NO) of BLA. Products derived from a possible hydrolysis of L-Arg (L-Orn and urea) or of L-NOHA (L-Cit, hydroxyurea and hydroxylamine) are also inactive toward BLA at concentrations up to 2 mM. The configuration of L-NOHA is important as D-NOHA is much less active, and its free -COOH and alpha-NH2 functions are required for recognition of BLA. L-NOHA is also a potent inhibitor of the arginase activity of rat liver homogenates and of murine macrophages (IC50 of 150 and 450 microM, respectively). These remarkable properties of L-NOHA could play a role in the modulation of the biosynthesis of the biological mediator NO by increasing local L-Arg concentrations.
Nω-羟基-L-精氨酸（L-NOHA）是纯化的牛肝精氨酸酶（BLA）催化L-精氨酸（L-Arg）水解生成L-鸟氨酸（L-Orn）的强效抑制剂。它似乎是迄今为止报道的最强效的精氨酸酶抑制剂之一（Ki = 150微摩尔）。一氧化氮合酶的其他产物对BLA要么无作用（NO2-、NO3-），要么是较弱的抑制剂（L-瓜氨酸（L-Cit）和NO）。源自L-Arg（L-Orn和尿素）或L-NOHA（L-Cit、羟基脲和羟胺）可能水解的产物在浓度高达2毫摩尔时对BLA也无活性。L-NOHA的构型很重要，因为D-NOHA活性低得多，其游离的-COOH和α-NH2官能团是被BLA识别所必需的。L-NOHA也是大鼠肝脏匀浆和小鼠巨噬细胞精氨酸酶活性的强效抑制剂（IC50分别为150和450微摩尔）。L-NOHA的这些显著特性可能通过增加局部L-Arg浓度在生物介质NO生物合成的调节中发挥作用。
