（-）-R-非诺洛芬：大鼠肝脏微粒体催化生成非诺洛芬辅酶A

(-)-R-fenoprofen: formation of fenoprofenyl-coenzyme A by rat liver microsomes.

作者信息

Benoit E, Delatour P, Olivier L, Caldwell J

机构信息

Unité associée de Toxicologie Métabolique et d'écotoxicologie INRA-ENVL, Ecole Nationale Vétérinaire de Lyon, Marcy l'Etoile, France.

出版信息

Biochem Pharmacol. 1995 May 26;49(11):1717-20. doi: 10.1016/0006-2952(94)00417-k.

DOI:10.1016/0006-2952(94)00417-k

PMID:7786313

Abstract

The thioesterification of fenoprofen (FPF) by rat liver microsomes has been studied using an HPLC method enabling direct quantification of the FPF-CoA produced. Over the concentration range studied (5-400 microM), studies showed the participation of a single CoA ligase in the formation of FPF-CoA, in contrast with the involvement of several isozymes with different affinities, that has been found with ibuprofen (IPF). The Km for the reaction was dependent upon the presence of non-ionic detergent, a concentration of 0.05% Triton X-100 reducing the Km from 397 to 20 microM although the detergent had no effect on Vmax. The microsomal long-chain fatty acid CoA ligase was markedly enantioselective towards (-)-R-FPF and the formation of (-)-R-FP-CoA was inhibited by both the (+)-S enantiomer and palmitic acid.

摘要

利用一种能够直接定量所产生的非诺洛芬辅酶A（FPF-CoA）的高效液相色谱法，对大鼠肝脏微粒体催化非诺洛芬（FPF）的硫酯化反应进行了研究。在所研究的浓度范围（5 - 400微摩尔）内，研究表明单一的辅酶A连接酶参与了FPF-CoA的形成，这与布洛芬（IPF）的情况不同，布洛芬的形成涉及几种具有不同亲和力的同工酶。该反应的米氏常数（Km）取决于非离子去污剂的存在，0.05% Triton X - 100的浓度可使Km从397微摩尔降至20微摩尔，尽管该去污剂对最大反应速度（Vmax）没有影响。微粒体长链脂肪酸辅酶A连接酶对(-)-R-FPF具有明显的对映体选择性，(+)-S对映体和棕榈酸均抑制(-)-R-FP-CoA的形成。