Nitisinone causes acquired tyrosinosis in alkaptonuria.


Journal

Journal of inherited metabolic disease
ISSN: 1573-2665
Titre abrégé: J Inherit Metab Dis
Pays: United States
ID NLM: 7910918

Informations de publication

Date de publication:
09 2020
Historique:
received: 30 11 2019
revised: 01 02 2020
accepted: 17 02 2020
pubmed: 23 2 2020
medline: 6 10 2021
entrez: 22 2 2020
Statut: ppublish

Résumé

For over two decades, nitisinone (NTBC) has been successfully used to manipulate the tyrosine degradation pathway and save the lives of many children with hereditary tyrosinaemia type 1. More recently, NTBC has been used to halt homogentisic acid accumulation in alkaptonuria (AKU) with evidence suggesting its efficacy as a disease modifying agent. NTBC-induced hypertyrosinaemia has been associated with cognitive impairment and potentially sight-threatening keratopathy. In the context of a non-lethal condition (ie, AKU), these serious risks call for an evaluation of the wider impact of NTBC on the tyrosine pathway. We hypothesised that NTBC increases the tyrosine pool size and concentrations in tissues. In AKU mice tyrosine concentrations of tissue homogenates were measured before and after treatment with NTBC. In humans, pulse injection with l-[

Identifiants

pubmed: 32083330
doi: 10.1002/jimd.12229
doi:

Substances chimiques

Cyclohexanones 0
Nitrobenzoates 0
Tyrosine 42HK56048U
Phenylalanine 47E5O17Y3R
nitisinone K5BN214699

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1014-1023

Informations de copyright

© 2020 SSIEM.

Références

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Auteurs

Milad Khedr (M)

Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospitals Trust, Liverpool, UK.
Department of Musculoskeletal Biology I, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Maggie S Cooper (MS)

Department of Radiopharmacy, Royal Liverpool University Hospitals Trust, Liverpool, UK.

Andrew T Hughes (AT)

Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospitals Trust, Liverpool, UK.
Department of Musculoskeletal Biology I, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Anna M Milan (AM)

Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospitals Trust, Liverpool, UK.
Department of Musculoskeletal Biology I, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Andrew S Davison (AS)

Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospitals Trust, Liverpool, UK.
Department of Musculoskeletal Biology I, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Brendan P Norman (BP)

Department of Musculoskeletal Biology I, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Hazel Sutherland (H)

School of Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK.

Jonathan C Jarvis (JC)

School of Sport and Exercise Sciences, Liverpool John Moores University, Liverpool, UK.

Richard Fitzgerald (R)

NIHR Royal Liverpool and Broadgreen Clinical Research Facility, Liverpool, UK.

Louise Markinson (L)

NIHR Royal Liverpool and Broadgreen Clinical Research Facility, Liverpool, UK.

Eftychia-Eirini Psarelli (EE)

Cancer Research UK Liverpool Cancer Trials Unit, University of Liverpool, Liverpool, UK.

Parisa Ghane (P)

Department of Electrical and Computer Engineering, Texas A&M University, College Station, Texas, USA.

Nicolaas E P Deutz (NEP)

Department of Health and Kinesiology, Centre for Translational Research in Aging & Longevity, Texas A&M University, College Station, Texas, USA.

James A Gallagher (JA)

Department of Musculoskeletal Biology I, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Lakshminarayan R Ranganath (LR)

Department of Clinical Biochemistry and Metabolic Medicine, Royal Liverpool University Hospitals Trust, Liverpool, UK.
Department of Musculoskeletal Biology I, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

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