Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism.
Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism.
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DOI：
10.1038/s42003-021-01909-5
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发表时间：
2021-03-19
影响因子：
5.9
通讯作者：
Martens J
中科院分区：
文献类型：
--
作者：
van Outersterp RE;Moons SJ;Engelke UFH;Bentlage H;Peters TMA;van Rooij A;Huigen MCDG;de Boer S;van der Heeft E;Kluijtmans LAJ;van Karnebeek CDM;Wevers RA;Berden G;Oomens J;Boltje TJ;Coene KLM;Martens J
疾病生物标志物的鉴定在开发先天性代谢缺陷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。苯丙酮尿症中积累的主要代谢物是苯丙氨酸，但其水平并不总是与临床结果直接相关。在这里，我们结合联合收割机红外离子光谱和核磁共振光谱，以确定苯丙氨酸-葡萄糖Amadori重排产物作为苯丙酮尿症的生物标志物。此外，我们发现类似的氨基酸-葡萄糖代谢物在患者的体液中形成，积累蛋氨酸，赖氨酸，脯氨酸和瓜氨酸。Amadori重排产物是形成晚期糖基化终产物的众所周知的中间体，并且与糖尿病和衰老的病理生理学相关，但现在显示也在氨基酸血症条件下形成。它们代表了氨基酸代谢先天性缺陷的一般代谢物类别，显示出作为生物标志物的潜力，并可能提供疾病病理生理学的进一步见解。Rianne货车Outersterp等人将联合收割机质谱、NMR和红外离子光谱法结合起来，以鉴定代谢紊乱（如苯丙酮尿症（PKU））患者血浆中的氨基酸-己糖结合物。这些缀合物或Amadori重排产物通常在未受影响个体的血液样品中检测不到，因此可能代表疾病生物标志物。
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. Rianne van Outersterp et al. combine mass spectrometry, NMR, and infrared ion spectroscopy to identify amino acid-hexose conjugates in the blood plasma from patients with metabolic disorders such as phenylketonuria (PKU). These conjugates, or Amadori rearrangement products, are generally not detectable in blood samples from unaffected individuals, and may therefore represent disease biomarkers.
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影响因子：
2.4
作者：
Jahja, Rianne;van der Meere, Jaap J.;van Spronsen, Francjan J.
通讯作者：
van Spronsen, Francjan J.
影响因子：
4.2
作者：
Coene, Karlien L. M.;Kluijtmans, Leo A. J.;Wevers, Ron A.
通讯作者：
Wevers, Ron A.
影响因子：
1.6
作者：
Martens, Jonathan;Berden, Giel;Oomens, Jos
通讯作者：
Oomens, Jos
影响因子：
15
作者：
Elferink, Hidde;Severijnen, Marion E.;Boltje, Thomas J.
通讯作者：
Boltje, Thomas J.
DOI：
10.1016/s0096-5332(08)60392-6
发表时间：
1955-01-01
期刊：
ADVANCES IN CARBOHYDRATE CHEMISTRY
影响因子：
--
作者：
HODGE, JE
通讯作者：
HODGE, JE