Pigmentation Chemistry and Radical-Based Collagen Degradation in Alkaptonuria and Osteoarthritic Cartilage
| Autor: | Lakshminarayan R. Ranganath, James A. Gallagher, Robert Bittl, Christian Teutloff, Melinda J. Duer, Hartmut Oschkinat, Brendan P. Norman, Wing Ying Chow, Norman B. Roberts |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Cartilage
Articular Magnetic Resonance Spectroscopy Collagen helix Osteoarthritis Alkaptonuria Catalysis fibrous proteins chemistry.chemical_compound Pigment NMR spectroscopy Spinal osteoarthropathy Fibrous Proteins | Hot Paper medicine Humans Homogentisic acid Homogentisic Acid Ochronosis Pigmentation Cartilage Communication 500 Naturwissenschaften und Mathematik::530 Physik::530 Physik Electron Spin Resonance Spectroscopy General Chemistry Pigments Biological medicine.disease radicals Communications medicine.anatomical_structure chemistry Biochemistry visual_art visual_art.visual_art_medium sense organs 600 Technik Medizin angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie Therapeutik Oxidation-Reduction metabolism EPR spectroscopy |
| Zdroj: | ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Angewandte Chemie (International ed. in English) Angewandte Chemie (International Ed. in English) |
| Popis: | 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. Alkaptonuria is a rare disease that leads to striking pigmentation and mechanical failure of cartilage tissue. DNP‐enhanced solid‐state NMR enabled us to observe disruption of interstrand hydrogen bonding in collagen proteins from alkaptonuria patient tissue. A mechanism involving transient glycyl radicals is proposed as basis of the degradation and pigmentation of cartilage tissue in alkaptonuria. |
| Databáze: | OpenAIRE |
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