Chow, Wing Ying 
ORCID: 0000-0003-0719-5958, Norman, Brendan P ORCID: 0000-0001-9293-4852, Roberts, Norman B, Ranganath, Lakshminarayan R ORCID: 0000-0002-4205-2269, Teutloff, Christian ORCID: 0000-0001-6949-1985, Bittl, Robert ORCID: 0000-0003-4103-3768, Duer, Melinda J ORCID: 0000-0002-9196-5072, Gallagher, James A ORCID: 0000-0002-0852-279X and Oschkinat, Hartmut ORCID: 0000-0002-4384-9544
(2020)
Pigmentierungschemie und radikalbasierter Kollagenabbau bei Alkaptonurie und Arthrose.
Angewandte Chemie, 132 (29).
pp. 12035-12040.
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 |
|---|---|
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 06 Jul 2021 08:34 |
| Last Modified: | 18 Jan 2023 21:36 |
| DOI: | 10.1002/ange.202000618 |
| Open Access URL: | https://doi.org/10.1002/ange.202000618 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3128978 |
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