致蛋白氨基酸与精神分裂症发病机制的整合

Medicine Advances Pub Date : 2024-06-14 DOI:10.1002/med4.65
Michelle S. Carvalho, Mauricio Luis Sforca, Silvana Aparecida Rocco, Danielle Zildeana Sousa Furtado, Cristiane da Silva Silverio, Marielle F. Queiroz Nunes, Marcel Vella Nunes, Marcelo P. Machado Adelino, Leonardo Afonso dos Santos, Andrea Jackowski, Rodrigo Affonseca Bressan, Acioly Luiz Tavares Lacerda, Nilson Antônio Assunção
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引用次数: 0

摘要

精神分裂症(SCZ)是一种多因素导致的严重精神障碍,氨基酸在其中的作用相对未知。基于SCZ患者与健康对照组(HCs)相比氨基酸水平失衡的假设,本研究旨在确定参与蛋白质合成的20种蛋白源氨基酸。通过质子核磁共振,我们确定了血清中 20 种氨基酸的蛋白合成水平。我们对 20 种氨基酸中的 19 种进行了血清水平鉴定。谷胱甘肽的主要前体半胱氨酸未被检测到。多变量探索性分析确定赖氨酸、色氨酸(TRP)和谷氨酸可能是SCZ的生物标志物。与 HCs 相比,SCZ 患者的赖氨酸和 TRP 水平较低,谷氨酸水平较高。在 SCZ 中观察到的血浆 TRP 水平的降低归因于犬尿氨酸途径的激活,并对血清素的合成产生了影响。在赖氨酸和TRP之间观察到了很强的正相关性,而在赖氨酸和谷氨酸之间观察到了很弱的负相关性。这一结果与赖氨酸催化过程一致,因为赖氨酸降解会产生谷氨酸,有利于多巴胺的增加。我们无法找到任何研究表明赖氨酸分解与 SCZ 病理生理学之间存在关系,但我们认为这种关联具有创新性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Integration of proteinogenic amino acids in the pathogenesis of schizophrenia

Integration of proteinogenic amino acids in the pathogenesis of schizophrenia

Background

Schizophrenia (SCZ) is a severe mental disorder of multifactorial origin in which the role of amino acids is relatively unknown. Based on the hypothesis that there is an imbalance in amino acid levels in individuals with SCZ compared with healthy controls (HCs), the aim of this study was to identify the 20 proteinogenic amino acids involved in protein synthesis.

Methods

This study included 43 sex- and age-matched individuals: 20 HCs and 23 with SCZ diagnosed using the Diagnostic and Statistical Manual of Mental Disorders criteria. Using proton nuclear magnetic resonance, we identified the serum levels of the 20 amino acids proteinogenic. We perform multivariate statistical exploratory analyzes to identify compounds, quantify, and identify the main biomarkers of SCZ.

Results

We identified the serum levels of 19 of the 20 amino acids. Cysteine, the main precursor of glutathione, was not detected. Multivariate exploratory analysis identified lysine, Tryptophan (TRP), and glutamate as possible biomarkers of SCZ. Both lysine and TRP levels were lower and glutamate levels were higher in individuals with SCZ than in HCs. The observed reduction in plasma TRP levels in SCZ was attributed to the activation of the kynurenine pathway and has implications for serotonin synthesis. A strong positive correlation was observed between lysine and TRP, and a weak negative correlation between lysine and glutamate. This result is consistent with the lysine catalysis process because lysine degradation generates glutamate and favors an increase in dopamine.

Conclusions

The results are consistent with the lysine catalysis process because lysine degradation generates glutamate and favors an increase in dopamine. We were unable to identify any studies suggesting a relationship between lysine catabolism and SCZ pathophysiology, but we recognize this association as innovative.

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