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关于“尿L-赤藓糖-β-羟基天冬酰胺——一种新型丝氨酸消旋酶抑制剂及锌离子依赖性D-丝氨酸脱水酶的底物”的述评

Commentary on "Urinary L-erythro-β-hydroxyasparagine - a novel serine racemase inhibitor and substrate of the Zn2+-dependent D-serine dehydratase".

作者信息

Tamaki Fabio Kendi

机构信息

University of Dundee, Dundee, United Kingdom.

出版信息

Biosci Rep. 2021 Nov 22. doi: 10.1042/BSR20211524.

DOI:10.1042/BSR20211524
PMID:34806751
Abstract

The analysis of the urine contents can be informative of physiological homeostasis, and it has been speculated that the levels of urinary D-serine (D-ser) could inform about neurological and renal disorders. By analysing the levels of urinary D-ser using a D-ser dehydratase (DSD) enzyme, Ito et al. have described abundant levels of L-β-EHAsn, a non-proteogenic amino acid which is also a newly described substrate for DSD. The data presented supports the endogenous production L-β-EHAsn, with its concentration significantly correlating with the concentration of creatinine in urine. Taken together, these results could raise speculations that L-β-EHAsn might have unexplored important biological roles. It has been demonstrated that L-β-EHAsn also inhibits serine racemase with Ki values (40 μM) similar to its concentration in urine (50 μM). Given that serine racemase is the enzyme involved in the synthesis of D-ser, and L-β-EHAsn is also a substrate for DSD, further investigations could verify if this amino acid would be involved in the metabolic regulation of pathways involving D-ser.

摘要

对尿液成分的分析可以反映生理稳态,并且据推测,尿液中D-丝氨酸(D-ser)的水平可以反映神经和肾脏疾病。通过使用D-丝氨酸脱水酶(DSD)分析尿液中D-丝氨酸的水平,伊藤等人发现了大量的L-β-EHAsn,这是一种非蛋白质氨基酸,也是一种新发现的DSD底物。所呈现的数据支持L-β-EHAsn的内源性产生,其浓度与尿液中肌酐的浓度显著相关。综合来看,这些结果可能引发推测,即L-β-EHAsn可能具有尚未被探索的重要生物学作用。已经证明,L-β-EHAsn也以与尿液中浓度(50μM)相似的Ki值(40μM)抑制丝氨酸消旋酶。鉴于丝氨酸消旋酶是参与D-丝氨酸合成的酶,并且L-β-EHAsn也是DSD的底物,进一步的研究可以验证这种氨基酸是否参与涉及D-丝氨酸的代谢途径的调节。

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