用于苯丙酮尿症饮食治疗的不含苯丙氨酸的重组营养蛋白。

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Yvonne Mücke, Natalia Jablonka, Nicole Rimann, Hiu Man Grisch-Chan, Bernhard Hoffmann, Stefan Schillberg, Beat Thöny, Stefan Rasche
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引用次数: 0

摘要

苯丙酮尿症(PKU)是一种先天性代谢性疾病,会导致全身苯丙氨酸(Phe)升高,而苯丙氨酸具有神经毒性和致畸性。目前,PKU 无法治愈,治疗方法是终生使用不含 Phe 的氨基酸混合物作为蛋白质限制饮食,这种饮食难以下咽。为了寻找一种适口的膳食替代品,我们发现了一种枯草芽孢杆菌蛋白(GSP16O),它具有均衡但低 Phe 的氨基酸谱。我们优化了序列,并在荧光假单胞菌中表达了不含Phe的改良版(GSP105),产量达到20克/升。纯化后的 GSP105 蛋白具有中性的味道和气味,可溶性高,在 80°C 以下仍保持稳定。用含有 GSP105 或正常蛋白质的食物喂养人类 PKU 模型--同基因 enu2 小鼠。GSP105 食物可使血液中的 Phe 含量和大脑中的单胺类神经递质代谢物恢复正常,并可预防母体 PKU。因此,GSP105饮食为PKU提供了另一种有效的饮食管理策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

A phenylalanine-free recombinant nutritional protein for the dietary management of phenylketonuria

A phenylalanine-free recombinant nutritional protein for the dietary management of phenylketonuria

Phenylketonuria (PKU) is a congenital metabolic disorder that causes the systemic elevation of phenylalanine (Phe), which is neurotoxic and teratogenic. PKU is currently incurable, and management involves lifelong adherence to an unpalatable protein-restricted diet based on Phe-free amino acid mixtures. Seeking a palatable dietary alternative, we identified a Bacillus subtilis protein (GSP16O) with a well-balanced but low-Phe amino acid profile. We optimized the sequence and expressed a modified Phe-free version (GSP105) in Pseudomonas fluorescens, achieving yields of 20 g/L. The purified GSP105 protein has a neutral taste and smell, is highly soluble, and remains stable up to 80°C. Homozygous enu2 mice, a model of human PKU, were fed with diets containing either GSP105 or normal protein. The GSP105 diet led to normalization of blood Phe levels and brain monoamine neurotransmitter metabolites, and prevented maternal PKU. The GSP105 diet thus provides an alternative and efficacious dietary management strategy for PKU.

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来源期刊
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease 医学-内分泌学与代谢
CiteScore
9.50
自引率
7.10%
发文量
117
审稿时长
4-8 weeks
期刊介绍: The Journal of Inherited Metabolic Disease (JIMD) is the official journal of the Society for the Study of Inborn Errors of Metabolism (SSIEM). By enhancing communication between workers in the field throughout the world, the JIMD aims to improve the management and understanding of inherited metabolic disorders. It publishes results of original research and new or important observations pertaining to any aspect of inherited metabolic disease in humans and higher animals. This includes clinical (medical, dental and veterinary), biochemical, genetic (including cytogenetic, molecular and population genetic), experimental (including cell biological), methodological, theoretical, epidemiological, ethical and counselling aspects. The JIMD also reviews important new developments or controversial issues relating to metabolic disorders and publishes reviews and short reports arising from the Society''s annual symposia. A distinction is made between peer-reviewed scientific material that is selected because of its significance for other professionals in the field and non-peer- reviewed material that aims to be important, controversial, interesting or entertaining (“Extras”).
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