Pigmentation Chemistry and Radical-Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage

Chow, Wing Ying, Norman, Brendan P ORCID: 0000-0001-9293-4852, Roberts, Norman B, Ranganath, Lakshminarayan R, Teutloff, Christian, Bittl, Robert, Duer, Melinda J, Gallagher, James A ORCID: 0000-0002-0852-279X and Oschkinat, Hartmut (2020) Pigmentation Chemistry and Radical-Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage. ANGEWANDTE CHEMIE-INTERNATIONAL EDITION, 59 (29). pp. 11937-11942.

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Abstract

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.

Item Type:	Article
Uncontrolled Keywords:	EPR spectroscopy, fibrous proteins, metabolism, NMR spectroscopy, radicals
Depositing User:	Symplectic Admin
Date Deposited:	01 Apr 2020 10:36
Last Modified:	18 Jan 2023 23:56
DOI:	10.1002/anie.202000618
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3081396

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• Pigmentation chemistry and radical-based collagen degradation in alkaptonuria and osteoarthritic cartilage. (deposited 31 Mar 2020 10:21)
  • Pigmentation Chemistry and Radical-Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage. (deposited 01 Apr 2020 10:36) [Currently Displayed]