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维生素B6缺乏会在果蝇中产生代谢改变。

Vitamin B6 deficiency produces metabolic alterations in Drosophila.

作者信息

Tesoriere Giulia, Pilesi Eleonora, De Rosa Michele, Giampaoli Ottavia, Patriarca Adriano, Spagnoli Mariangela, Chiocciolini Federica, Tramonti Angela, Contestabile Roberto, Sciubba Fabio, Vernì Fiammetta

机构信息

Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, 00185, Rome, Italy.

Department of Chemistry, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185, Rome, Italy.

出版信息

Metabolomics. 2025 Mar 23;21(2):42. doi: 10.1007/s11306-025-02236-0.

Abstract

INTRODUCTION

Pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6 is involved in 4% of cellular enzymatic activities and its deficiency is responsible for or contributes to several human diseases. The study of underlying mechanisms is still in its infancy and requires suitable model organisms. In Drosophila the deficiency of vitamin B6 produces chromosome aberrations and hallmarks of human diseases including diabetes and cancer. However, the effects of vitamin B6 deficiency have never been examined at a metabolic level.

OBJECTIVES

This study evaluates the metabolic changes in vitamin B6 deficient Drosophila larvae with the aim of validating flies as a suitable model for diseases associated to vitamin B6 deficiency.

METHODS

To induce vitamin B6 deficiency we fed Drosophila wild type larvae with 4-deoxypyridoxine (4DP), a PLP antagonist. By HPLC analysis we verified that the 4DP treatment was effective in inducing vitamin B6 deficiency. Using an NMR-based metabolomic approach we compared the metabolites in larval extracts from untreated and 4DP-fed larvae.

RESULTS

The NMR spectra analysis identified quantitative differences for sixteen metabolites out of forty, including branched chain and aromatic amino acids, glucose, and lipids, thus revealing interesting possible associations with the phenotypes showed by vitamin B6 deficient flies.

CONCLUSIONS

Our results validate Drosophila as a suitable model to study in depth the molecular mechanisms underlying human diseases associated with vitamin B6 deficiency and confirmed that 4DP treatment is effective in inducing vitamin B6 deficiency.

摘要

引言

磷酸吡哆醛(PLP)是维生素B6的生物活性形式,参与4%的细胞酶活性,其缺乏会导致或促成多种人类疾病。对其潜在机制的研究仍处于起步阶段,需要合适的模式生物。在果蝇中,维生素B6缺乏会导致染色体畸变以及包括糖尿病和癌症在内的人类疾病特征。然而,维生素B6缺乏的影响从未在代谢水平上进行过研究。

目的

本研究评估维生素B6缺乏的果蝇幼虫的代谢变化,旨在验证果蝇作为与维生素B6缺乏相关疾病的合适模型。

方法

为诱导维生素B6缺乏,我们用PLP拮抗剂4-脱氧吡哆醇(4DP)喂养果蝇野生型幼虫。通过高效液相色谱分析,我们验证了4DP处理在诱导维生素B6缺乏方面是有效的。使用基于核磁共振的代谢组学方法,我们比较了未处理幼虫和4DP喂养幼虫的幼虫提取物中的代谢物。

结果

核磁共振光谱分析确定了四十种代谢物中的十六种存在定量差异,包括支链和芳香族氨基酸、葡萄糖和脂质,从而揭示了与维生素B6缺乏果蝇所表现出的表型可能存在的有趣关联。

结论

我们的结果验证了果蝇作为深入研究与维生素B6缺乏相关人类疾病潜在分子机制的合适模型,并证实4DP处理在诱导维生素B6缺乏方面是有效的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cae0/11930875/ccf042d3b453/11306_2025_2236_Fig1_HTML.jpg

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