谷氨酰胺转氨酶的作用K (GTK)在大脑中的硫和alpha-keto酸代谢,和可能的神经中毒bioactivation。

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库珀AJ

谷氨酰胺转氨酶的作用K (GTK)在大脑中的硫和alpha-keto酸代谢,和可能的神经中毒bioactivation。

Neurochem Int。2004年6月,44 (8):557 - 77。

PubMed ID

15016471 (在PubMed

]

文摘

谷氨酰胺转氨酶K (GTK),这是一个自由的可逆的谷氨酰胺(蛋氨酸)芳香族氨基酸转氨酶,存在于大多数哺乳动物的组织,包括大脑。定量,最重要的胺捐赠者体内谷氨酰胺。谷氨酰胺转氨作用(即的产物。alpha-ketoglutaramate;alphaKGM)正迅速被alpha-ketoglutarate环合和/或转换。转氨作用因此“拉”的方向谷氨酰胺的利用率。GTK的主要生理作用是维持低水平的phenylpyruvate和关闭蛋氨酸救助途径。GTK也催化的转氨作用胱硫醚、lanthionine thialysine到相应的alpha-keto酸,使环化酮亚胺。环酮亚胺和一些代谢物中发现由此派生的大脑。目前尚不清楚这些化合物有一个生物功能或代谢死角。然而,高亲和性结合lanthionine酮亚胺(路)大脑膜已被报道。 Mammalian tissues possess several enzymes capable of catalyzing transamination of kynurenine in vitro. Two of these kynurenine aminotransferases (KATs), namely KAT I and KAT II, are present in brain and have been extensively studied. KAT I and KAT II are identical to GTK and alpha-aminoadipate aminotransferase, respectively. GTK/KAT I is largely cytosolic in kidney, but mostly mitochondrial in brain. The same gene codes for both forms, but alternative splicing dictates whether a 32-amino acid mitochondrial-targeting sequence is present in the expressed protein. The activity of KAT I is altered by a missense mutation (E61G) in the spontaneously hypertensive rat. The symptoms may be due in part to alteration of kynurenine transamination. However, owing to strong competition from other amino acid substrates, the turnover of kynurenine to kynurenate by GTK/KAT I in nervous tissue must be slow unless kynurenine and GTK are sequestered in a compartment distinct from the major amino acid pools. The possibility is discussed that the spontaneous hypertension in rats carrying the GTK/KAT I mutation may be due in part to disruption of glutamine transamination. GTK is one of several pyridoxal 5'-phosphate (PLP)-containing enzymes that can catalyze non-physiological beta-elimination reactions with cysteine S-conjugates containing a good leaving group attached at the sulfur. These elimination reactions may contribute to the bioactivation of certain electrophiles, resulting in toxicity to kidney, liver, brain, and possibly other organs. On the other hand, the beta-lyase reaction catalyzed by GTK may be useful in the conversion of some cysteine S-conjugate prodrugs to active components in vivo. The roles of GTK in (a) brain nitrogen, sulfur, and aromatic amino acid/kynurenine metabolism, (b) brain alpha-keto acid metabolism, (c) bioactivation of certain electrophiles in brain, (d) prodrug targeting, and (e) maintenance of normal blood pressure deserve further study.

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药物靶点

药物	目标	类	生物	药理作用	行动
磷酸吡哆醛	犬尿氨酸/ alpha-aminoadipate转氨酶,线粒体	蛋白质	人类	未知的	代数余子式	细节