Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia.
Glycine cleavage system: reaction mechanism, physiological significance, and hyperglycinemia.
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DOI：
10.2183/pjab.84.246
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Hiraga K
中科院分区：
文献类型：
--
作者：
Kikuchi G;Motokawa Y;Yoshida T;Hiraga K
甘氨酸裂解系统催化以下可逆反应：甘氨酸裂解系统广泛分布于动物、植物和细菌中，由三种固有成分和一种常见成分组成：i) P-蛋白，一种含磷酸吡哆醛的蛋白质，ii) T-蛋白，四氢叶酸依赖性反应所需的蛋白质，iii) H-蛋白，一种携带氨甲基中间体然后通过假体硫辛酰基部分携带氢的蛋白质， iv) L-蛋白，一种常见的硫辛酰胺脱氢酶。在动物和植物中，蛋白质形成与线粒体内膜松散结合的酶复合物。在酶促反应中，H 蛋白将 P 蛋白（其本身是一种潜在的 α-氨基酸脱羧酶）转化为活性酶，并与 T 蛋白形成复合物。在甘氨酸裂解和合成中，与H-蛋白的硫辛酸结合的氨甲基部分代表在T-蛋白的作用下降解为或可以由N5,N10-亚甲基-H4叶酸和氨形成的中间体。 N5,N10-亚甲基-H4叶酸用于各种细胞物质的生物合成，例如嘌呤、胸苷酸和甲硫氨酸，甲硫氨酸是通过S-腺苷甲硫氨酸的主要甲基供体。这解释了甘氨酸裂解系统作为包括人类在内的各种脊椎动物丝氨酸和甘氨酸分解代谢中最重要的途径的生理重要性。非酮症高甘氨酸血症是人类婴儿的一种先天性代谢紊乱，是由甘氨酸裂解活性缺陷引起的。大多数非酮症高甘氨酸血症患者的 P 蛋白基因有损伤，而有些患者的 T 蛋白基因有突变。唯一被归类为退行性非酮症高甘氨酸血症的患者的 H 蛋白不含假体硫辛酰残基。正常T蛋白的晶体学以及正常和突变T蛋白重组体的生化特征证实了突变T蛋白失去酶活性的原因。讨论了细胞损伤的假定机制，包括非酮症高甘氨酸血症患者中枢神经系统的细胞损伤。
The glycine cleavage system catalyzes the following reversible reaction: The glycine cleavage system is widely distributed in animals, plants and bacteria and consists of three intrinsic and one common components: those are i) P-protein, a pyridoxal phosphate-containing protein, ii) T-protein, a protein required for the tetrahydrofolate-dependent reaction, iii) H-protein, a protein that carries the aminomethyl intermediate and then hydrogen through the prosthetic lipoyl moiety, and iv) L-protein, a common lipoamide dehydrogenase. In animals and plants, the proteins form an enzyme complex loosely associating with the mitochondrial inner membrane. In the enzymatic reaction, H-protein converts P-protein, which is by itself a potential α–amino acid decarboxylase, to an active enzyme, and also forms a complex with T-protein. In both glycine cleavage and synthesis, aminomethyl moiety bound to lipoic acid of H-protein represents the intermediate that is degraded to or can be formed from N5,N10-methylene-H4folate and ammonia by the action of T-protein. N5,N10-Methylene-H4folate is used for the biosynthesis of various cellular substances such as purines, thymidylate and methionine that is the major methyl group donor through S-adenosyl-methionine. This accounts for the physiological importance of the glycine cleavage system as the most prominent pathway in serine and glycine catabolism in various vertebrates including humans. Nonketotic hyperglycinemia, a congenital metabolic disorder in human infants, results from defective glycine cleavage activity. The majority of patients with nonketotic hyperglycinemia had lesions in the P-protein gene, whereas some had mutant T-protein genes. The only patient classified into the degenerative type of nonketotic hyperglycinemia had an H-protein devoid of the prosthetic lipoyl residue. The crystallography of normal T-protein as well as biochemical characterization of recombinants of the normal and mutant T-proteins confirmed why the mutant T-proteins had lost enzyme activity. Putative mechanisms of cellular injuries including those in the central nervous system of patients with nonketotic hyperglycinemia are discussed.
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影响因子：
4.8
作者：
Fujiwara, K;Toma, S;Taniguchi, H
通讯作者：
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影响因子：
15.9
作者：
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3.2
作者：
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4.1
作者：
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4.1
作者：
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