Shebl, Nourhan;
El-Jaafary, Shaimaa;
Saeed, Ayman A;
Elkafrawy, Passent;
El-Sayed, Amr;
Shamma, Samir;
Elnemr, Rasha;
... Salama, Mohamed; + view all
(2024)
Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort.
Frontiers in Molecular Biosciences
, 11
, Article 1341950. 10.3389/fmolb.2024.1341950.
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Abstract
Introduction: Parkinson’s disease (PD) is the most common motor neurodegenerative disease worldwide. Given the complexity of PD etiology and the different metabolic derangements correlated to the disease, metabolomics profiling of patients is a helpful tool to identify patho-mechanistic pathways for the disease development. Dopamine metabolism has been the target of several previous studies, of which some have reported lower phenylalanine and tyrosine levels in PD patients compared to controls. // Methods: In this study, we have collected plasma from 27 PD patients, 18 reference controls, and 8 high-risk controls to perform a metabolomic study using liquid chromatography-electrospray ionization–tandem mass spectrometry (LC-ESI-MS/MS). // Results: Our findings revealed higher intensities of trans-cinnamate, a phenylalanine metabolite, in patients compared to reference controls. Thus, we hypothesize that phenylalanine metabolism has been shifted to produce trans-cinnamate via L-phenylalanine ammonia lyase (PAL), instead of producing tyrosine, a dopamine precursor, via phenylalanine hydroxylase (PAH). // Discussion: Given that these metabolites are precursors to several other metabolic pathways, the intensities of many metabolites such as dopamine, norepinephrine, and 3-hydroxyanthranilic acid, which connects phenylalanine metabolism to that of tryptophan, have been altered. Consequently, and in respect to Metabolic Control Analysis (MCA) theory, the levels of tryptophan metabolites have also been altered. Some of these metabolites are tryptamine, melatonin, and nicotinamide. Thus, we assume that these alterations could contribute to the dopaminergic, adrenergic, and serotonergic neurodegeneration that happen in the disease.
| Type: | Article |
|---|---|
| Title: | Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.3389/fmolb.2024.1341950 |
| Publisher version: | http://dx.doi.org/10.3389/fmolb.2024.1341950 |
| Language: | English |
| Additional information: | Copyright © 2024 Shebl, El-Jaafary, Saeed, Elkafrawy, El-Sayed, Shamma, Elnemr, Mekky, Mohamed, Kittaneh, El-Fawal, Rizig and Salama. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY), https://creativecommons.org/licenses/by/4.0/. The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
| Keywords: | Trans-cinnamate, phenylalanine, dopamine, tyrosine, metabolomics, PD, PAL, PAH |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10189857 |
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