Radboud University, Institute for Molecules and Materials, FELIX Laboratory, Toernooiveld 7, Nijmegen, the Netherlands.
Radboud University, Institute for Molecules and Materials, Synthetic Organic Chemistry, Nijmegen, the Netherlands.
Commun Biol. 2021 Mar 19;4(1):367. doi: 10.1038/s42003-021-01909-5.
The identification of disease biomarkers plays a crucial role in developing diagnostic strategies for inborn errors of metabolism and understanding their pathophysiology. A primary metabolite that accumulates in the inborn error phenylketonuria is phenylalanine, however its levels do not always directly correlate with clinical outcomes. Here we combine infrared ion spectroscopy and NMR spectroscopy to identify the Phe-glucose Amadori rearrangement product as a biomarker for phenylketonuria. Additionally, we find analogous amino acid-glucose metabolites formed in the body fluids of patients accumulating methionine, lysine, proline and citrulline. Amadori rearrangement products are well-known intermediates in the formation of advanced glycation end-products and have been associated with the pathophysiology of diabetes mellitus and ageing, but are now shown to also form under conditions of aminoacidemia. They represent a general class of metabolites for inborn errors of amino acid metabolism that show potential as biomarkers and may provide further insight in disease pathophysiology.
疾病生物标志物的鉴定在开发代谢性遗传病的诊断策略和理解其病理生理学方面起着至关重要的作用。在先天性苯丙酮尿症中积累的一种主要代谢物是苯丙氨酸，然而其水平并不总是与临床结果直接相关。在这里，我们结合红外离子光谱和 NMR 光谱鉴定出苯丙氨酸-葡萄糖麦拉德重排产物作为苯丙酮尿症的生物标志物。此外，我们还发现了在积累蛋氨酸、赖氨酸、脯氨酸和瓜氨酸的患者体液中形成的类似氨基酸-葡萄糖代谢物。麦拉德重排产物是形成晚期糖基化终产物的众所周知的中间产物，与糖尿病和衰老的病理生理学有关，但现在也表明它们在氨基酸血症的情况下形成。它们代表了一类氨基酸代谢性遗传病的代谢物，具有作为生物标志物的潜力，并可能为疾病病理生理学提供进一步的见解。
