Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism

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 dire...

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Published inCommunications biology Vol. 4; no. 1; p. 367
Main Authors van Outersterp, Rianne E, Moons, Sam J, Engelke, Udo F H, Bentlage, Herman, Peters, Tessa M A, van Rooij, Arno, Huigen, Marleen C D G, de Boer, Siebolt, van der Heeft, Ed, Kluijtmans, Leo A J, van Karnebeek, Clara D M, Wevers, Ron A, Berden, Giel, Oomens, Jos, Boltje, Thomas J, Coene, Karlien L M, Martens, Jonathan
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 19.03.2021
Nature Publishing Group UK
Nature Portfolio
Subjects
Advanced glycosylation end products
Aging
Amadori compounds
Amino acids
Biology
Biomarkers
Body fluids
Citrulline
Diabetes mellitus
Glycosylation
Hexose
Inborn errors of metabolism
Intermediates
Lysine
Magnetic resonance spectroscopy
Mass spectroscopy
Metabolic disorders
Metabolism
Metabolites
Methionine
NMR
Nuclear magnetic resonance
Pathophysiology
Phenylalanine
Phenylketonuria
Proline
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Abstract 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.
AbstractList 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.
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.
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.
Abstract 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.
ArticleNumber 367
Author Coene, Karlien L M
van Rooij, Arno
Wevers, Ron A
Moons, Sam J
Engelke, Udo F H
de Boer, Siebolt
Peters, Tessa M A
Berden, Giel
Bentlage, Herman
Martens, Jonathan
van der Heeft, Ed
van Outersterp, Rianne E
Boltje, Thomas J
Oomens, Jos
van Karnebeek, Clara D M
Huigen, Marleen C D G
Kluijtmans, Leo A J
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Snippet The identification of disease biomarkers plays a crucial role in developing diagnostic strategies for inborn errors of metabolism and understanding their...
Abstract The identification of disease biomarkers plays a crucial role in developing diagnostic strategies for inborn errors of metabolism and understanding...
Rianne van Outersterp et al. combine mass spectrometry, NMR, and infrared ion spectroscopy to identify amino acid-hexose conjugates in the blood plasma from...
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SubjectTerms Advanced glycosylation end products
Aging
Amadori compounds
Amino acids
Biology
Biomarkers
Body fluids
Citrulline
Diabetes mellitus
Glycosylation
Hexose
Inborn errors of metabolism
Intermediates
Lysine
Magnetic resonance spectroscopy
Mass spectroscopy
Metabolic disorders
Metabolism
Metabolites
Methionine
NMR
Nuclear magnetic resonance
Pathophysiology
Phenylalanine
Phenylketonuria
Proline
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Title Amadori rearrangement products as potential biomarkers for inborn errors of amino-acid metabolism
URI https://www.ncbi.nlm.nih.gov/pubmed/33742102
https://www.proquest.com/docview/2503046591/abstract/
https://search.proquest.com/docview/2503447875
https://pubmed.ncbi.nlm.nih.gov/PMC7979741
https://doaj.org/article/a3702831608e413ca3c44c8e50fdc0d3
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