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三羧酸循环(TCA)和糖酵解中间产物对常氧和低氧近端小管中甘氨酸 - 丝氨酸相互转化的调节作用。

Modulation of glycine-serine interconversion by TCA and glycolytic intermediates in normoxic and hypoxic proximal tubules.

作者信息

Cowin G J, Willgoss D A, Endre Z H

机构信息

Department of Medicine, University of Queensland, Royal Brisbane Hospital, Australia.

出版信息

Biochim Biophys Acta. 1996 Jan 10;1310(1):41-7. doi: 10.1016/0167-4889(95)00141-7.

DOI:10.1016/0167-4889(95)00141-7
PMID:9244173
Abstract

Glycine-serine interconversion is important to numerous metabolic processes and serine release by the kidney. Incubation of freshly isolated rat renal proximal tubules with 5 mM glycine 75% 13C-labelled in the 2-position resulted in 13C-labelled incorporation into serine of 69 micromol.g protein(-1) (+/- 14, n = 16) at 20 min. Addition of 5 mM glucose, 4 mM lactate, 1 mM alanine, 1 mM butyrate and 1 mM glutamate increased 13C-label incorporation into serine to 173 micromol.g protein(-1) (+/- 32, n = 4) at 60 min, 50% greater than tubules incubated with 5 mM glycine alone (P < 0.05). The increase was prevented by hypoxia. Reoxygenation for 20 min restored the rate of incorporation of 13C-label into serine. The fraction of unlabelled serine remained approximately 47% at 20, 40 and 60 min in each group. The results indicate that in the presence of oxygen, TCA and glycolytic intermediates stimulate serine synthesis via the glycine cleavage complex and serine hydroxymethyltransferase pathways and not the phosphorylated pathway. In addition, significant serine production occurs from an unidentified source, which is also tightly coupled to glycine metabolism. Both in the presence and absence of added TCA and glycolytic intermediates, glycine was the principle source of the methylene group in methylene tetrahydrofolate.

摘要

甘氨酸 - 丝氨酸的相互转化对众多代谢过程及肾脏丝氨酸释放至关重要。将新鲜分离的大鼠肾近端小管与2位75% 13C标记的5 mM甘氨酸一起孵育,20分钟时13C标记掺入丝氨酸的量为69微摩尔·克蛋白-1(±14,n = 16)。添加5 mM葡萄糖、4 mM乳酸、1 mM丙氨酸、1 mM丁酸和1 mM谷氨酸后,60分钟时13C标记掺入丝氨酸的量增加至173微摩尔·克蛋白-1(±32,n = 4),比仅用5 mM甘氨酸孵育的小管高出50%(P < 0.05)。缺氧可阻止这种增加。复氧20分钟可恢复13C标记掺入丝氨酸的速率。每组中未标记丝氨酸的比例在20、40和60分钟时均保持在约47%。结果表明,在有氧条件下,三羧酸循环(TCA)和糖酵解中间产物通过甘氨酸裂解复合物和丝氨酸羟甲基转移酶途径而非磷酸化途径刺激丝氨酸合成。此外,丝氨酸还从一个不明来源大量产生,且该来源也与甘氨酸代谢紧密相关。无论是否添加TCA和糖酵解中间产物,甘氨酸都是亚甲基四氢叶酸中亚甲基基团的主要来源。

相似文献

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Modulation of glycine-serine interconversion by TCA and glycolytic intermediates in normoxic and hypoxic proximal tubules.三羧酸循环(TCA)和糖酵解中间产物对常氧和低氧近端小管中甘氨酸 - 丝氨酸相互转化的调节作用。
Biochim Biophys Acta. 1996 Jan 10;1310(1):41-7. doi: 10.1016/0167-4889(95)00141-7.
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Serine isotopmer analysis by 13C-NMR defines glycine-serine interconversion in situ in the renal proximal tubule.通过13C-NMR进行的丝氨酸异构体分析确定了肾近端小管中甘氨酸-丝氨酸的原位相互转化。
Biochim Biophys Acta. 1996 Jan 10;1310(1):32-40. doi: 10.1016/0167-4889(95)00142-5.
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Serine synthesis in rat kidney: studies with perfused kidney and cortical tubules.大鼠肾脏中的丝氨酸合成:灌注肾脏和皮质肾小管的研究
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Relationships between intracellular amino acid levels and protection against injury to isolated proximal tubules.细胞内氨基酸水平与离体近端肾小管损伤防护之间的关系。
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