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Pigmentation Chemistry and Radical‐Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage
Author(s) -
Chow Wing Ying,
Norman Brendan P.,
Roberts Norman B.,
Ranganath Lakshminarayan R.,
Teutloff Christian,
Bittl Robert,
Duer Melinda J.,
Gallagher James A.,
Oschkinat Hartmut
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202000618
Subject(s) - alkaptonuria , ochronosis , homogentisic acid , cartilage , chemistry , radical , pigment , osteoarthritis , biochemistry , anatomy , pathology , biology , medicine , organic chemistry , alternative medicine
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.