实验性抗肿瘤药物卡拉西胺对脑胆碱乙酰转移酶的影响。

The effect of the experimental antitumor agent caracemide on brain choline acetyltransferase.

作者信息

Ho B T, Tansey L W, Feiffer R, Newman R A, Farquhar D, Fields W S, Krakoff I H

机构信息

Department of Neuro-Oncology, U.T.M.D. Anderson Hospital, Houston 77030.

出版信息

J Neurosci Res. 1988;19(1):119-21. doi: 10.1002/jnr.490190116.

DOI:10.1002/jnr.490190116

PMID:3343703

Abstract

Caracemide was found to inhibit choline acetyltransferase (CAT) from rat brain. A concentration of 0.5 mM caracemide inhibited the enzyme by 93%, whereas a degradation product from caracemide, N-(methylcarbamoyloxy)acetamide, produced only a 50% inhibition. Two other degradation products, N-(methyl-carbamoyloxy)-N'-methylurea and N-hydroxy-N'-methylurea, lacked any inhibitory activity. With bovine brain CAT, caracemide showed noncompetitive inhibition with the substrate choline, Km 337 microM, Ki240 microM, Vmax 2.83 nmol acetylcholine formed/min/mg protein and mixed inhibition with the substrate acetyl-CoA, Km 21 microM, Ki 146 microM, Vmax 3.85 nmol acetylcholine formed/min/mg protein.

摘要

发现卡醋胺可抑制大鼠脑内的胆碱乙酰转移酶（CAT）。浓度为0.5 mM的卡醋胺可使该酶活性抑制93%，而卡醋胺的一种降解产物N -（甲基氨基甲酰氧基）乙酰胺仅产生50%的抑制作用。另外两种降解产物N -（甲基氨基甲酰氧基）-N'-甲基脲和N -羟基-N'-甲基脲则没有任何抑制活性。对于牛脑CAT，卡醋胺对底物胆碱表现为非竞争性抑制，Km为337 microM，Ki为240 microM，Vmax为每分钟每毫克蛋白质形成2.83 nmol乙酰胆碱；对底物乙酰辅酶A表现为混合抑制，Km为21 microM，Ki为146 microM，Vmax为每分钟每毫克蛋白质形成3.85 nmol乙酰胆碱。