TY - JOUR
T1 - Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism
AU - van Outersterp, R.E.
AU - Moons, S.J.
AU - Engelke, U.F.H.
AU - Bentlage, H.
AU - Peters, T.M.A.
AU - van Rooij, A.
AU - Huigen, M.C.D.G.
AU - de Boer, S.
AU - van der Heeft, E.
AU - Kluijtmans, L.A.J.
AU - van Karnebeek, C.D.M.
AU - Wevers, R.A.
AU - Berden, G.
AU - Oomens, J.
AU - Boltje, T.J.
AU - Coene, K.L.M.
AU - Martens, J.
N1 - With supplementary files.
PY - 2021/3/19
Y1 - 2021/3/19
N2 - 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.
AB - 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.
UR - https://pure.uva.nl/ws/files/68321636/Supplementary_files.zip
UR - http://www.scopus.com/inward/record.url?scp=85102890833&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s42003-021-01909-5
DO - https://doi.org/10.1038/s42003-021-01909-5
M3 - Article
C2 - 33742102
SN - 2399-3642
VL - 4
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 367
ER -