Van der Werf P, Stephani R A, Orlowski M, Meister A
Proc Natl Acad Sci U S A. 1973 Mar;70(3):759-61. doi: 10.1073/pnas.70.3.759.
L-2-Imidazolidone-4-carboxylic acid is an effective competitive inhibitor of the reaction catalyzed by 5-oxoprolinase, in which 5-oxo-L-proline (L-pyroglutamic acid, L-2-pyrrolidone-5-carboxylic acid, L-5-oxopyrrolidine-2-carboxylic acid) is converted to L-glutamate, with concomitant cleavage of ATP to ADP and orthophosphate. L-2-Imidazolidone-4-carboxylate decreased the rate of metabolism of 5-oxo-L-[(14)C]proline to (14)CO(2) by rat-kidney slices but had no effect on the metabolism of [(14)C]glutamate. Mice injected with L-2-imidazolidone-4-carboxylate exhibited greatly reduced ability to metabolize 5-oxo-L-proline, but metabolized glutamate at an essentially normal rate. The findings provide an approach to an animal model for the human condition 5-oxoprolinuria, in which there is apparently a deficiency of renal 5-oxoprolinase activity. The evidence indicates that 5-oxoproline is a normal metabolite.
L-2-咪唑烷酮-4-羧酸是5-氧代脯氨酸酶催化反应的一种有效竞争性抑制剂,在该反应中,5-氧代-L-脯氨酸(L-焦谷氨酸、L-2-吡咯烷酮-5-羧酸、L-5-氧代吡咯烷-2-羧酸)转化为L-谷氨酸,同时ATP裂解为ADP和正磷酸盐。L-2-咪唑烷酮-4-羧酸盐降低了大鼠肾切片将5-氧代-L-[(14)C]脯氨酸代谢为(14)CO2的速率,但对[(14)C]谷氨酸的代谢没有影响。注射了L-2-咪唑烷酮-4-羧酸盐的小鼠代谢5-氧代-L-脯氨酸的能力大大降低,但代谢谷氨酸的速率基本正常。这些发现为人类疾病5-氧代脯氨酸尿症提供了一种建立动物模型的方法,在该疾病中,肾脏5-氧代脯氨酸酶活性显然缺乏。证据表明5-氧代脯氨酸是一种正常代谢产物。