ArticleJournal of inherited metabolic disease2011
Redox-proteomics of the effects of homogentisic acid in an in vitro human serum model of alkaptonuric ochronosis.
Article in Journal of inherited metabolic disease, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- Quantification of the flux of tyrosine pathway metabolites during nitisinone treatment of Alkaptonuria.Scientific reports · 2019Trial
- Plasma Proteomic Signatures in Alkaptonuria.Biology · 2026Article
- HGA-Induced Oxidative Stress Impairs Autophagy via Lysosomal Dysfunction in Alkaptonuria.Antioxidants (Basel, Switzerland) · 2026Article
- An in vitro cell model for exploring inflammatory and amyloidogenic events in alkaptonuria.Journal of cellular physiology · 2024Article
- Review
- Alkaptonuria.Nature reviews. Disease primers · 2024Review
- Article
- Association of alkaptonuria and low dose nitisinone therapy with cataract formation in a large cohort of patients.JIMD reports · 2022Article
- Computational Approaches Integrated in a Digital Ecosystem Platform for a Rare Disease.Frontiers in molecular medicine · 2022Review
- A molecular spectroscopy approach for the investigation of early phase ochronotic pigment development in Alkaptonuria.Scientific reports · 2021Article
- Fatal acute haemolysis and methaemoglobinaemia in a man with renal failure and Alkaptonuria - Is nitisinone the solution?Molecular genetics and metabolism reports · 2020Article
- Machine learning application for development of a data-driven predictive model able to investigate quality of life scores in a rare disease.Orphanet journal of rare diseases · 2020Article
- Interactive alkaptonuria database: investigating clinical data to improve patient care in a rare disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Evaluation of the serum metabolome of patients with alkaptonuria before and after two years of treatment with nitisinone using LC-QTOF-MS.JIMD reports · 2019Article
- Reduced primary cilia length and altered Arl13b expression are associated with deregulated chondrocyte Hedgehog signaling in alkaptonuria.Journal of cellular physiology · 2017Article
- Old treatments for new insights and strategies: proposed management in adults and children with alkaptonuria.Journal of inherited metabolic disease · 2015Review
- Homogentisate 1,2 dioxygenase is expressed in brain: implications in alkaptonuria.Journal of inherited metabolic disease · 2015Article
- Amyloidosis in alkaptonuria.Journal of inherited metabolic disease · 2015Review
- The Pigment in Alkaptonuria Relationship to Melanin and Other Coloured Substances: A Review of Metabolism, Composition and Chemical Analysis.JIMD reports · 2015Article
- Diagnosis of secondary amyloidosis in alkaptonuria.Diagnostic pathology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Alkaptonuria (AKU) is a rare inborn error of metabolism associated with a deficient activity of homogentisate 1,2-dioxygenase (HGO), an enzyme involved in tyrosine and phenylalanine metabolism. Such a deficiency leads to the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in connective tissues, where melanin-like pigments accumulate (ochronosis). Ochronosis involves especially joints, where an ochronotic arthropathy develops. Little is known on the molecular mechanisms leading to ochronosis and ochronotic arthropathy in AKU. Previous works of ours showed that HGA in vitro propagates oxidative stress through its conversion into benzoquinone acetate (BQA). We hence used an in vitro model consisting of human serum treated with HGA and evaluated the activities of glutathione related anti-oxidant enzymes and levels of compounds indexes of oxidative stress. Proteomics and redox-proteomics were used to identify oxidized proteins and proteins more likely able to bind BQA. Overall, we found that the production of ochronotic pigment in HGA-treated serum is accompanied by lipid peroxidation, decreased activity of the enzyme glutathione peroxidase and massive depletion of thiol groups, together with increased protein carbonylation and thiol oxidation. We also found that BQA was likely to bind carrier proteins and naturally abundant serum proteins, eventually altering their chemico-physical properties. Concluding, our work points towards a critical importance of thiol compounds in counteracting HGA- and BQA- mediated stress in AKU, so that future research for disease biomarkers and pharmacological treatments for AKU and ochronosis will be more easily addressed.
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Registered trials
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