Summary of Study ST002296

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 PR001471. The data can be accessed directly via it's Project DOI: 10.21228/M8KH70 This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

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.

Perform statistical analysis  |  Show all samples  |  Show named metabolites  |  Download named metabolite data  
Download mwTab file (text)   |  Download mwTab file(JSON)   |  Download data files (Contains raw data)
Study IDST002296
Study TitleComprehensive biotransformation analysis of phenylalanine-tyrosine metabolism reveals alternative routes of metabolite clearance in nitisinone-treated alkaptonuria (Serum metabolomic analysis)
Study TypeSerum metabolomic analysis (study 1 of 2)
Study SummaryBackground: Metabolomic analyses in alkaptonuria (AKU) have recently revealed alternative pathways in phenylalanine-tyrosine (phe-tyr) metabolism from biotransformation of homo-gentisic acid (HGA), the active molecule in this disease. The aim of this research was to study the phe-tyr metabolic pathway and whether the metabolites upstream of HGA, increased in nitisinone-treated patients, also undergo phase 1 and 2 biotransformation reactions. Methods: Metabolomic analyses were performed on serum and urine from patients partaking in the SONIA 2 phase 3 international randomised-controlled trial of nitisinone in AKU (EudraCT no. 2013-001633-41). Serum and urine samples were taken from the same patients at baseline (pre-nitisinone) then at 24 and 48 months on nitisinone treatment (patients N = 47 serum; 53 urine) or no treatment (patients N = 45 serum; 50 urine). Targeted feature extraction was per-formed to specifically mine data for the entire complement of theoretically predicted phase 1 and 2 biotransformation products derived from phenylalanine, tyrosine, 4-hydroxyphenylpyruvic acid and 4-hydroxyphenyllactic acid, in addition to phenylalanine-derived metabolites with known increases in phenylketonuria. Results: In total, we ob-served 13 phase 1 and 2 biotransformation products from phenylalanine through to HGA. Each of these products were observed in urine and two were detected in serum. The derivatives of the metabolites upstream of HGA were markedly increased in urine of nitisinone-treated patients (fold change 1.2-16.2) and increases in 12 of these compounds were directly proportional to the degree of nitisinone-induced hypertyrosinaemia (correlation coefficient with serum tyrosine = 0.2-0.7). Increases in the urinary phenylalanine metabolites were also observed across consecutive visits in the treated group. Conclusions: Nitisinone treatment results in marked increases in a wider network of phe-tyr metabolites than shown before. This network comprises alternative biotransformation products from the major metabolites of this pathway, produced by reactions including hydration (phase 1) and bioconjugation (phase 2) of acetyl, methyl, acetylcysteine, glucuronide, glycine and sulfate groups. We propose that these alternative routes of phe-tyr metabolism, predominantly in urine, minimise tyrosinaemia as well as phenylalanaemia.
Institute
University of Liverpool Institute of Life Course & Medical Sciences
DepartmentDepartment of Musculoskeletal & Ageing Science
Last NameBrendan
First NameNorman
AddressWilliam Henry Duncan Building, 6 West Derby Street, Liverpool, UK. L7 8TX
Emailbnorman@liverpool.ac.uk
Phone+447809606497
Submit Date2022-09-26
Num Groups2
Total Subjects92
Num Males59
Num Females33
Raw Data AvailableYes
Raw Data File Type(s)d
Analysis Type DetailLC-MS
Release Date2022-10-14
Release Version1
Norman Brendan Norman Brendan
https://dx.doi.org/10.21228/M8KH70
ftp://www.metabolomicsworkbench.org/Studies/ application/zip

Select appropriate tab below to view additional metadata details:

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id local_sample_id Trial arm
SA220373P40_V4Treated
SA220374P40_V1Treated
SA220375P39_V6Treated
SA220376P40_V6Treated
SA220377L35_V4Treated
SA220378L33_V6Treated
SA220379L35_V1Treated
SA220380P39_V4Treated
SA220381L35_V6Treated
SA220382P36_V6Treated
SA220383L6_V1Treated
SA220384L6_V4Treated
SA220385L6_V6Treated
SA220386L40_V6Treated
SA220387L40_V4Treated
SA220388L33_V4Treated
SA220389P36_V4Treated
SA220390L40_V1Treated
SA220391P39_V1Treated
SA220392L30_V6Treated
SA220393P46_V1Treated
SA220394P44_V6Treated
SA220395P44_V4Treated
SA220396P46_V4Treated
SA220397P46_V6Treated
SA220398P47_V6Treated
SA220399P47_V4Treated
SA220400P47_V1Treated
SA220401L28_V1Treated
SA220402P26_V4Treated
SA220403L30_V1Treated
SA220404L30_V4Treated
SA220405L7_V1Treated
SA220406P43_V1Treated
SA220407P43_V4Treated
SA220408L28_V6Treated
SA220409P44_V1Treated
SA220410P43_V6Treated
SA220411L33_V1Treated
SA220412L7_V6Treated
SA220413P30_V4Treated
SA220414P30_V1Treated
SA220415P3_V6Treated
SA220416P2_V6Treated
SA220417P2_V4Treated
SA220418P18_V4Treated
SA220419P18_V6Treated
SA220420P2_V1Treated
SA220421P3_V4Treated
SA220422P3_V1Treated
SA220423P23_V6Treated
SA220424P26_V6Treated
SA220425P26_V1Treated
SA220426P23_V4Treated
SA220427P23_V1Treated
SA220428P22_V1Treated
SA220429P22_V4Treated
SA220430P22_V6Treated
SA220431P18_V1Treated
SA220432P30_V6Treated
SA220433F1_V1Treated
SA220434P34_V6Treated
SA220435P11_V1Treated
SA220436P36_V1Treated
SA220437L8_V6Treated
SA220438P48_V1Treated
SA220439L8_V1Treated
SA220440L8_V4Treated
SA220441P11_V4Treated
SA220442P11_V6Treated
SA220443P31_V6Treated
SA220444P31_V4Treated
SA220445P31_V1Treated
SA220446P15_V6Treated
SA220447P15_V4Treated
SA220448P34_V4Treated
SA220449P34_V1Treated
SA220450P15_V1Treated
SA220451L7_V4Treated
SA220452L28_V4Treated
SA220453F29_V6Treated
SA220454P55_V6Treated
SA220455L19_V6Treated
SA220456F29_V4Treated
SA220457F29_V1Treated
SA220458F26_V1Treated
SA220459F26_V4Treated
SA220460F26_V6Treated
SA220461F31_V1Treated
SA220462F31_V4Treated
SA220463F5_V4Treated
SA220464F5_V6Treated
SA220465P55_V1Treated
SA220466F5_V1Treated
SA220467F4_V6Treated
SA220468F31_V6Treated
SA220469F4_V1Treated
SA220470F4_V4Treated
SA220471F24_V6Treated
SA220472F24_V4Treated
Showing page 1 of 3     Results:    1  2  3  Next     Showing results 1 to 100 of 276
  logo