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D-serine-A useful biomarker for renal injury?
Acta Physiologica ( IF 5.6 ) Pub Date : 2020-07-03 , DOI: 10.1111/apha.13531
Kameliya Spasova 1 , Michael Fähling 1
Affiliation  

Nature is full of miracles. One such phenomenon is the existence of enantiomers, molecules that are mirror images of each other. Chirality is widespread and stereoisomers exhibit similar physical and chemical properties, however, are not identical and may have strikingly different physiological effects. One example is Thalidomide, a sedative marketed as Contergan® from 1957 to 1961 by the German company Chemie Grünenthal. The racemate caused abnormalities in children being born to mothers using this drug against morning sickness during pregnancy. Later, it turned out that the L‐enantiomer was a good sedative, whereas the D‐form was harmful.

Here, we will focus on D‐serine, a non‐essential amino acid and enantiomer of L‐serine. It is emerging as a potential biomarker for kidney disease that can be detected in both blood and urine.

Endogenous D‐serine has a neuromodulatory role. It is vital for synapse development and for physiological function of the nervous system. D‐serine was proven to be a ligand for the glycine site of the N‐methyl D‐Aspartate (NMDA) receptor and is synthesized from L‐serine in the brain.1 As a potent agonist of the receptor, D‐serine is considered to be a potential therapeutic agent in schizophrenia and major depressive disorders,1 linked to hypo‐function of NMDA receptor‐mediated signalling.2 Notably, in a clinical study with patients at high risk of schizophrenia, 10% of the participants in the group receiving D‐serine orally were withdrawn because of massive renal damage, which has been attributed to the treatment.3

Measurements of D‐enantiomers are challenging because they share the same physical properties with the L‐enantiomers.1 Mothet et al emphasized the importance that researchers validate the specificity of their detection through suitable controls.1 Nowadays, 2D high‐performance liquid chromatography (HPLC) is one of the methods of choice for a precise measurement of D‐amino acids.

Nephropathies are characterized as loss of kidney function due to renal disease or kidney damage.4 Many publications, issued recently in Acta Physiologica, cover diverse areas of the extensive field of kidney research. Among these are studies about renal haemodynamics,5-7 about potential prevention of acute kidney injury8 or promising treatment of chronic kidney disease.9, 10 Investigations to understand, diagnose and treat renal diseases and renal damage are necessary and important for patients, society and public health care.4 Moreover, biomarkers for fast and clear‐cut detection of origin and location of renal damage still need to be established.



中文翻译:

D-丝氨酸-一种有用的肾损伤生物标志物?

大自然充满了奇迹。其中一种现象是对映异构体的存在,即彼此互为镜像的分子。手性很普遍,立体异构体表现出相似的物理和化学性质,但并不完全相同,可能具有截然不同的生理效应。一个例子是沙利度胺,一种镇静剂,从 1957 年到 1961 年由德国公司 Chemie Grünenthal以 Contergan ®销售。外消旋体在怀孕期间使用这种药物治疗孕吐的母亲所生的孩子造成异常。后来发现 L-对映异构体是一种很好的镇静剂,而 D-对映异构体是有害的。

在这里,我们将关注 D-丝氨酸,一种非必需氨基酸和 L-丝氨酸的对映异构体。它正在成为肾脏疾病的潜在生物标志物,可以在血液和尿液中检测到。

内源性 D-丝氨酸具有神经调节作用。它对突触发育和神经系统的生理功能至关重要。D-丝氨酸被证明是 N-甲基 D-天冬氨酸 (NMDA) 受体甘氨酸位点的配体,由大脑中的 L-丝氨酸合成。1作为受体的有效激动剂,D-丝氨酸被认为是精神分裂症和重度抑郁症的潜在治疗剂,1与 NMDA 受体介导的信号传导功能低下有关。2值得注意的是,在一项针对精神分裂症高危患者的临床研究中,口服 D-丝氨酸组中 10% 的参与者因严重肾损伤而退出,这归因于治疗。3

D-对映异构体的测量具有挑战性,因为它们与 L-对映异构体具有相同的物理特性。1 Mothet 等人强调了研究人员通过合适的控制来验证其检测特异性的重要性。1如今,二维高效液相色谱 (HPLC) 是精确测量 D-氨基酸的首选方法之一。

肾病的特征是由于肾病或肾损伤导致肾功能丧失。4最近在 Acta Physiologica 上发表的许多出版物涵盖了肾脏研究广泛领域的各个领域。其中包括关于肾血流动力学的研究5-7关于急性肾损伤的潜在预防8或有希望治疗慢性肾病的研究。9, 10了解、诊断和治疗肾脏疾病和肾脏损害的调查对于患者、社会和公共卫生保健来说是必要和重要的。4此外,仍需要建立快速明确检测肾损伤起源和位置的生物标志物。

更新日期:2020-09-10
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