Untargeted Metabolomics Reveals Dysregulation of Glycine- and Serine-Coupled Metabolic Pathways in an ALDH1L1-Dependent Manner In Vivo

丝氨酸 甘氨酸 代谢途径 下调和上调 新陈代谢 生物化学 谷胱甘肽 化学 氨基酸 代谢组学 生物 细胞生物学 生物信息学 基因
作者
Geng-Shen Fu,Sabrina Molina,Sergey A. Krupenko,Susan Sumner,Blake R. Rushing
出处
期刊:Metabolites [Multidisciplinary Digital Publishing Institute]
卷期号:14 (12): 696-696
标识
DOI:10.3390/metabo14120696
摘要

Background: ALDH1L1 plays a crucial role in folate metabolism, regulating the flow of one-carbon groups through the conversion of 10-formyltetrahydrofolate to tetrahydrofolate and CO2 in a NADP+-dependent reaction. The downregulation of ALDH1L1 promotes malignant tumor growth, and silencing of ALDH1L1 is commonly observed in many cancers. In a previous study, Aldh1l1 knockout (KO) mice were found to have an altered liver metabotype, including significant alterations in glycine and serine. Serine and glycine play crucial roles in pathways linked to cancer initiation and progression, including one-carbon metabolism. Objective/Methods: To further investigate the metabolic role of ALDH1L1, an untargeted metabolomic analysis was conducted on the liver and plasma of both KO and wild-type (WT) male and female mice. Since ALDH1L1 affects glycine- and serine-coupled metabolites and metabolic pathways, correlation analyses between liver glycine and serine with other liver or plasma metabolites were performed for both WT and KO mice. Significantly correlated metabolites were input into MetaboAnalyst 5.0 for pathway analysis to uncover metabolic pathways coupled with serine and glycine in the presence or absence of ALDH1L1 expression. Results: This analysis showed substantial alterations in pathways associated with glycine and serine following ALDH1L1 loss, including the amino acid metabolism, antioxidant pathways, fatty acid oxidation, and vitamin B5 metabolism. These results indicate the glycine- and serine-linked metabolic reprogramming following ALDH1L1 loss to support macromolecule biosynthesis and antioxidant defense. Additional research is required to further explore the correlation between specific alterations in these pathways and tumor growth, as well as to identify potential dietary interventions to mitigate the detrimental effects of ALDH1L1 loss.

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