Lombardini J B, Sufrin J R
Biochem Pharmacol. 1983 Feb 1;32(3):489-95. doi: 10.1016/0006-2952(83)90528-2.
Two isozymes of ATP:L-methionine S-adenosyltransferase (MAT) were fractionated from rat Novikoff solid hepatoma. Their Km values for L-methionine and/or their inhibition constants for various L-methionine analogues were significantly different from the kinetic constants obtained for three isozymes fractionated from normal rat liver. Ki values for cycloleucine and (+/-)-2-aminobicyclo[2.1.1]hexane-2-carboxylic acid, presented for each tumor and liver isozyme, indicate that (+/-)-2-aminobicyclo[2.1.1]hexane-2-carboxylic acid was the more potent inhibitor. Dixon plots were also used to test a series of amino acid analogues [cycloleucine, 1-aminocyclobutanecarboxylic acid, 1-aminocyclohexanecarboxylic acid, (+/-)-2-aminobicyclo[2.1.1]hexane-2-carboxylic acid, L-2-amino-4-hexynoic acid, (Z)-L-2-amino-5-chloro-trans-4-hexenoic acid, L-ethionine, S-n-propyl-DL-homocysteine, S-n-butyl-DL-homocysteine, and seleno-DL-ethionine] of methionine for inhibitory potency. Fixed L-methionine concentrations were used to determine the concentration of inhibitor necessary to inhibit the MAT reaction by 50%. Differential inhibitory activities of the amino acid analogues were noted between the tumor and rat liver isozymes thus supporting the suggestion that tumor-derived MAT isozymes may provide an exploitable target for cancer chemotherapy.
从大鼠诺维科夫实体肝癌中分离出了两种ATP：L-甲硫氨酸S-腺苷转移酶（MAT）同工酶。它们对L-甲硫氨酸的Km值和/或对各种L-甲硫氨酸类似物的抑制常数与从正常大鼠肝脏中分离出的三种同工酶所获得的动力学常数显著不同。针对每种肿瘤和肝脏同工酶给出的环亮氨酸和（±）-2-氨基双环[2.1.1]己烷-2-羧酸的Ki值表明，（±）-2-氨基双环[2.1.1]己烷-2-羧酸是更有效的抑制剂。狄克逊图也用于测试一系列甲硫氨酸的氨基酸类似物[环亮氨酸、1-氨基环丁烷羧酸、1-氨基环己烷羧酸、（±）-2-氨基双环[2.1.1]己烷-2-羧酸、L-2-氨基-4-己炔酸、（Z）-L-2-氨基-5-氯反式-4-己烯酸、L-乙硫氨酸、S-正丙基-DL-高半胱氨酸、S-正丁基-DL-高半胱氨酸和硒代-DL-乙硫氨酸]的抑制效力。使用固定的L-甲硫氨酸浓度来确定将MAT反应抑制50%所需的抑制剂浓度。在肿瘤和大鼠肝脏同工酶之间观察到氨基酸类似物的差异抑制活性，因此支持了肿瘤来源的MAT同工酶可能为癌症化疗提供可利用靶点的观点。
