Summary of project PR001387

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench,, where it has been assigned Project ID PR001387. The data can be accessed directly via it's Project DOI: 10.21228/M8FB0C This work is supported by NIH grant, U2C- DK119886.


Project ID: PR001387
Project DOI:doi: 10.21228/M8FB0C
Project Title:Impact of nitisinone on the cerebrospinal fluid metabolome of a murine model of alkaptonuria
Project Summary:Background: Nitisinone induced hypertyrosinaemia is well documented in Alkaptonuria (AKU), and there is uncertainty over whether it may contribute to a decline in cognitive function and or mood by altering neurotransmitter metabolism. The aim of this work was to evaluate the impact of nitisinone on the cerebrospinal fluid (CSF) metabolome in a murine model of AKU, with a view to providing additional insight into metabolic changes that occur following treatment with nitisinone. Methods: 17 CSF samples were collected from BALB/c Hgd-/-mice (n=8, treated with nitisinone – 4 mg/L and n=9, no treatment). Samples were diluted 1:1 with deionised water and analysed using a 1290 Infinity II liquid chromatography system coupled to a 6550 quadrupole time-of-flight mass spectrometry (Agilent, Cheadle, UK). Raw data were processed using a targeted feature extraction algorithm and an established in-house accurate mass retention time database. Matched entities (±10 ppm theoretical accurate mass and ±0.3 minutes retention time window) were filtered based on their frequency and variability. Experimental groups were compared using a moderated t-test with Benjamini-Hochberg false-discovery rate adjustment. Results: Tyrosine, acetyl-tyrosine, γ-glutamyl-tyrosine, p-hydroxyphenylacetic acid and 3-(4-hydroxyphenyl)lactic acid were shown to increase in abundance (log2 fold change 2.6-6.9, 3/5 were significant p<0.05) in the mice that received nitisinone. Several other metabolites of interest were matched but no significant differences were observed, including the aromatic amino acids phenylalanine and tryptophan, and monoamine metabolites adrenaline, 3-methoxy-4-hydroxyphenylglycol and octopamine. Conclusions: Evaluation of the CSF metabolome of a murine model of AKU showed a significant difference in the abundance of a limited number of metabolites. None of these have been reported in CSF from a murine model of AKU previously. Moreover this study confirms that some monoamine metabolites do not appear to be altered following nitisinone therapy.
Institute:University of Liverpool Institute of Life Course & Medical Sciences
Last Name:Davison
First Name:Andrew
Address:1. Department of Clinical Biochemistry and Metabolic Medicine, Liverpool Clinical Laboratories, Liverpool University Hospitals NHS Foundation Trust, Liverpool, UK; 2. Department of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool, UK 3. School of Exercise Science, Liverpool John Moores University, Liverpool, UK
Phone:0151 706 4011
Contributors:Davison AS1,2,*, Norman BP2, Sutherland H2,3, Milan AM1,2, Jarvis JC3, Gallagher JA2, Ranganath LR1,2

Summary of all studies in project PR001387

Study IDStudy TitleSpeciesInstituteAnalysis
(* : Contains Untargted data)
(* : Contains raw data)
ST002179 Impact of nitisinone on the cerebrospinal fluid metabolome of a murine model of alkaptonuria Mus musculus University of Liverpool Institute of Life Course & Medical Sciences MS 2022-06-08 1 33 Uploaded data (104.7G)*