Summary of Study ST002179

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, 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.

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This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study IDST002179
Study TitleImpact of nitisinone on the cerebrospinal fluid metabolome of a murine model of alkaptonuria
Study SummaryBackground: 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 NameDavison
First NameAndrew
Address1. 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
Emailandrew.davison@liverpoolft.nhs.uk
Phone0151 706 4011
Submit Date2022-05-13
Num Groups2
Total Subjects17
Raw Data AvailableYes
Raw Data File Type(s)d, mzML
Analysis Type DetailLC-MS
Release Date2022-06-08
Release Version1
Andrew Davison Andrew Davison
https://dx.doi.org/10.21228/M8FB0C
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

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Combined analysis:

Analysis ID AN003568 AN003569
Analysis type MS MS
Chromatography type Reversed phase Reversed phase
Chromatography system Agilent Infinity II Agilent Infinity II
Column Atlantis dC18 (3.0x100mm,3m,Waters,UK) Atlantis dC18 (3.0x100mm,3m,Waters,UK)
MS Type ESI ESI
MS instrument type Triple quadrupole Triple quadrupole
MS instrument name Agilent 6550 QTOF Agilent 6550 QTOF
Ion Mode POSITIVE NEGATIVE
Units area area

Chromatography:

Chromatography ID:CH002639
Chromatography Summary:Liquid chromatography (LC) was performed on an Agilent 1290 Infinity II LC system. An Atlantis dC18 column (3.0x100mm, 3µm, Waters, UK) was maintained at 60°C with a flow rate of 0.4mL/min. Mobile phases were (A) water and (B) methanol both containing 5mmol/L ammonium formate and 0.1% formic acid. The elution gradient started at 5% mobile phase B at 0-1 min increasing linearly to 100% B by 12 min, held at 100% B until 14 min, returning to 95% A for 5 min to recondition the column. Injection volume was 1µL.
Instrument Name:Agilent Infinity II
Column Name:Atlantis dC18 (3.0x100mm,3m,Waters,UK)
Column Temperature:60
Flow Gradient:The elution gradient started at 5% mobile phase B at 0-1 min increasing linearly to 100% B by 12 min, held at 100% B until 14 min, returning to 95% A for 5 min to recondition the column
Flow Rate:0.4mL/min
Solvent A:100% water; 0.1% formic acid; 5 mM ammonium formate
Solvent B:100% acetonitrile; 0.1% formic acid;5 mM ammonium formate
Chromatography Type:Reversed phase
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