Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort
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...
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| Format: | Article |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1341950/full |
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| author | Nourhan Shebl Shaimaa El-Jaafary Shaimaa El-Jaafary Ayman A. Saeed Passent Elkafrawy Amr El-Sayed Samir Shamma Rasha Elnemr Jaidaa Mekky Lobna A. Mohamed Omar Kittaneh Hassan El-Fawal Mie Rizig Mohamed Salama Mohamed Salama Mohamed Salama |
| author_facet | Nourhan Shebl Shaimaa El-Jaafary Shaimaa El-Jaafary Ayman A. Saeed Passent Elkafrawy Amr El-Sayed Samir Shamma Rasha Elnemr Jaidaa Mekky Lobna A. Mohamed Omar Kittaneh Hassan El-Fawal Mie Rizig Mohamed Salama Mohamed Salama Mohamed Salama |
| author_sort | Nourhan Shebl |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-25T02:15:14Z |
| format | Article |
| id | doaj.art-ab3166e376eb444794d5c117fb209b2c |
| institution | Directory Open Access Journal |
| issn | 2296-889X |
| language | English |
| last_indexed | 2024-04-25T02:15:14Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-ab3166e376eb444794d5c117fb209b2c2024-03-07T10:18:14ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2024-03-011110.3389/fmolb.2024.13419501341950Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohortNourhan Shebl0Shaimaa El-Jaafary1Shaimaa El-Jaafary2Ayman A. Saeed3Passent Elkafrawy4Amr El-Sayed5Samir Shamma6Rasha Elnemr7Jaidaa Mekky8Lobna A. Mohamed9Omar Kittaneh10Hassan El-Fawal11Mie Rizig12Mohamed Salama13Mohamed Salama14Mohamed Salama15Institute of Global Health and Human Ecology (I-GHHE), The American University in Cairo, Cairo, EgyptNeurology Department, Faculty of Medicine, Cairo University, Giza, EgyptGlobal Brain Health Institute (GBHI), Trinity College Dublin, Dublin, IrelandApplied Organic Chemistry Department, Chemical Industries Research Institute, National Research Centre (NRC), Giza, EgyptTechnology and Energy Research Center, Effat University-College of Engineering-NSMTU, Jeddah, Saudi ArabiaSocial Research Center, The American University in Cairo, Cairo, EgyptInstitute of Global Health and Human Ecology (I-GHHE), The American University in Cairo, Cairo, EgyptClimate Change Information Center & Expert Systems (CCICES), Agriculture Research Center, Giza, EgyptNeurology Department, Faculty of Medicine, Alexandria University, Alexandria, EgyptNeurology Department, Faculty of Medicine, Alexandria University, Alexandria, EgyptTechnology and Energy Research Center, Effat University-College of Engineering-NSMTU, Jeddah, Saudi ArabiaInstitute of Global Health and Human Ecology (I-GHHE), The American University in Cairo, Cairo, EgyptQueen Square, Institute of Neurology, University College London, London, United KingdomInstitute of Global Health and Human Ecology (I-GHHE), The American University in Cairo, Cairo, EgyptGlobal Brain Health Institute (GBHI), Trinity College Dublin, Dublin, Ireland0Faculty of Medicine, Mansoura University, Mansoura, EgyptIntroduction: 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.https://www.frontiersin.org/articles/10.3389/fmolb.2024.1341950/fulltrans-cinnamatephenylalaninedopaminetyrosinemetabolomicsPD |
| spellingShingle | Nourhan Shebl Shaimaa El-Jaafary Shaimaa El-Jaafary Ayman A. Saeed Passent Elkafrawy Amr El-Sayed Samir Shamma Rasha Elnemr Jaidaa Mekky Lobna A. Mohamed Omar Kittaneh Hassan El-Fawal Mie Rizig Mohamed Salama Mohamed Salama Mohamed Salama Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort Frontiers in Molecular Biosciences trans-cinnamate phenylalanine dopamine tyrosine metabolomics PD |
| title | Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort |
| title_full | Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort |
| title_fullStr | Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort |
| title_full_unstemmed | Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort |
| title_short | Metabolomic profiling reveals altered phenylalanine metabolism in Parkinson’s disease in an Egyptian cohort |
| title_sort | metabolomic profiling reveals altered phenylalanine metabolism in parkinson s disease in an egyptian cohort |
| topic | trans-cinnamate phenylalanine dopamine tyrosine metabolomics PD |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1341950/full |
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