Pigmentation Chemistry and Radical-Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage.
EPR spectroscopy
NMR spectroscopy
fibrous proteins
metabolism
radicals
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
13 07 2020
13 07 2020
Historique:
received:
15
01
2020
pubmed:
29
3
2020
medline:
26
3
2021
entrez:
29
3
2020
Statut:
ppublish
Résumé
Alkaptonuria (AKU) is a rare disease characterized by high levels of homogentisic acid (HGA); patients suffer from tissue ochronosis: dark brown pigmentation, especially of joint cartilage, leading to severe early osteoarthropathy. No molecular mechanism links elevated HGA to ochronosis; the pigment's chemical identity is still not known, nor how it induces joint cartilage degradation. Here we give key insight on HGA-derived pigment composition and collagen disruption in AKU cartilage. Synthetic pigment and pigmented human cartilage tissue both showed hydroquinone-resembling NMR signals. EPR spectroscopy showed that the synthetic pigment contains radicals. Moreover, we observed intrastrand disruption of collagen triple helix in pigmented AKU human cartilage, and in cartilage from patients with osteoarthritis. We propose that collagen degradation can occur via transient glycyl radicals, the formation of which is enhanced in AKU due to the redox environment generated by pigmentation.
Identifiants
pubmed: 32219972
doi: 10.1002/anie.202000618
pmc: PMC7383862
doi:
Substances chimiques
Pigments, Biological
0
Homogentisic Acid
NP8UE6VF08
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
11937-11942Subventions
Organisme : Medical Research Council
ID : MR/M01066X/1
Pays : United Kingdom
Informations de copyright
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
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