通过给予L-2-氧代噻唑烷-4-羧酸（一种5-氧代-L-脯氨酸酶底物）刺激肝脏谷胱甘肽的形成。
Stimulation of hepatic glutathione formation by administration of L-2-oxothiazolidine-4-carboxylate, a 5-oxo-L-prolinase substrate.
作者信息
Williamson J M, Meister A
出版信息
Proc Natl Acad Sci U S A. 1981 Feb;78(2):936-9. doi: 10.1073/pnas.78.2.936.
Abstract
5-Oxo-L-prolinase, the enzyme that catalyzes the conversion of 5-oxo-L-proline to L-glutamate coupled to the cleavage of ATP to ADP and Pi, also acts on L-2-oxothiazolidine-4-carboxylate (an analog of 5-oxoproline in which the 4-methylene moiety is replaced by sulfur) and ATP to yield cysteine and ADP. The enzyme, which exhibits an affinity for the analog similar to that for the natural substrate, is inhibited by the analog in vitro and in vivo. L-2-oxothiazolidine-4-carboxylate thus serves as a potent inhibitor of the gamma-glutamyl cycle at the step of 5-oxoprolinase. Administration of L-2-oxothiazolidine-4-carboxylate to mice that had been depleted of hepatic glutathione led to restoration of normal hepatic glutathione levels. Since L-2-oxothiazolidine-4-carboxylate is an excellent substrate of the enzyme, it may serve as an intracellular delivery system for cysteine and thus has potential as a therapeutic agent for conditions in which there is depletion of hepatic glutathione.
摘要
5-氧代-L-脯氨酸酶可催化5-氧代-L-脯氨酸转化为L-谷氨酸，并偶联ATP水解为ADP和磷酸，该酶也作用于L-2-氧代噻唑烷-4-羧酸（5-氧代脯氨酸的类似物，其中4-亚甲基部分被硫取代）和ATP，生成半胱氨酸和ADP。该酶对该类似物的亲和力与对天然底物的亲和力相似，在体外和体内均受到该类似物的抑制。因此，L-2-氧代噻唑烷-4-羧酸在5-氧代脯氨酸酶步骤中作为γ-谷氨酰循环的有效抑制剂。给肝谷胱甘肽耗竭的小鼠施用L-2-氧代噻唑烷-4-羧酸可使肝谷胱甘肽水平恢复正常。由于L-2-氧代噻唑烷-4-羧酸是该酶的优良底物，它可作为半胱氨酸的细胞内递送系统，因此有潜力作为治疗肝谷胱甘肽耗竭病症的治疗剂。
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THE CONVERSION OF CARBON TETRACHLORIDE AND CHLOROFORM TO CARBON DIOXIDE BY RAT LIVER HOMOGENATES.大鼠肝脏匀浆将四氯化碳和氯仿转化为二氧化碳的过程。
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Accumulation of 5-oxoproline in mouse tissues after inhibition of 5-oxoprolinase and administration of amino acids: evidence for function of the gamma-glutamyl cycle.5-氧脯氨酸酶抑制及氨基酸给药后小鼠组织中5-氧脯氨酸的积累：γ-谷氨酰循环功能的证据
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The metabolic formation and utilization of 5-oxo-L-proline (L-pyroglutamate, L-pyrrolidone carboxylate).5-氧代-L-脯氨酸（L-焦谷氨酸、L-吡咯烷酮羧酸）的代谢生成与利用。
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