title: LC-MS-based urinary metabolite signatures in idiopathic Parkinson's disease.
abstract: Increasing evidence has shown that abnormal metabolic phenotypes in body fluids reflect the pathogenesis and pathophysiology of Parkinson's disease (PD). These body fluids include urine; however, the relationship between, specifically, urinary metabolic phenotypes and PD is not fully understood. In this study, urinary metabolites from a total of 401 clinical urine samples collected from 106 idiopathic PD patients and 104 normal control subjects were profiled by using high-performance liquid chromatography coupled to high-resolution mass spectrometry. Our study revealed significant correlation between clinical phenotype and urinary metabolite profile. Metabolic profiles of idiopathic PD patients differed significantly and consistently from normal controls, with related metabolic pathway variations observed in steroidogenesis, fatty acid beta-oxidation, histidine metabolism, phenylalanine metabolism, tryptophan metabolism, nucleotide metabolism, and tyrosine metabolism. In the fruit fly Drosophila melanogaster, the alteration of the kynurenine pathway in tryptophan metabolism corresponded with pathogenic changes in the alpha-synuclein overexpressed Drosophila model of PD. The results suggest that LC-MS-based urinary metabolomic profiling can reveal the metabolite signatures and related variations in metabolic pathways that characterize PD. Consistent PD-related changes across species may provide the basis for understanding metabolic regulation of PD at the molecular level.
authors.affiliation: Department of Chemistry, Hong Kong Baptist University , Science Tower T1304, Hong Kong SAR, China.
authors.forename: Hemi
authors.initials: H
authors.lastname: Luan
authors.forename: Liang-Feng
authors.initials: LF
authors.lastname: Liu
authors.forename: Nan
authors.initials: N
authors.lastname: Meng
authors.forename: Zhi
authors.initials: Z
authors.lastname: Tang
authors.forename: Ka-Kit
authors.initials: KK
authors.lastname: Chua
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Chen
authors.forename: Ju-Xian
authors.initials: JX
authors.lastname: Song
authors.forename: Vincent C T
authors.initials: VC
authors.lastname: Mok
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Xie
authors.forename: Min
authors.initials: M
authors.lastname: Li
authors.forename: Zongwei
authors.initials: Z
authors.lastname: Cai
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine*; D002853:Chromatography, Liquid; D004331:Drosophila melanogaster; D005227:Fatty Acids / Q000378:metabolism; D006639:Histidine / Q000378:metabolism; D006801:Humans; D007737:Kynurenine / Q000378:metabolism; D013058:Mass Spectrometry; D055432:Metabolomics / Q000379:methods*; D009711:Nucleotides / Q000378:metabolism; D010300:Parkinson Disease / Q000175:diagnosis* / Q000652:urine*; D010641:Phenotype; D010649:Phenylalanine / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis; D014364:Tryptophan / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005227:Fatty Acids; D009711:Nucleotides; D013256:Steroids; D051844:alpha-Synuclein; D007737:Kynurenine; D014443:Tyrosine; D010649:Phenylalanine; D006639:Histidine; D014364:Tryptophan
keywords: drosophila; idiopathic Parkinson’s disease; metabolic phenotype; metabolite signatures; urinary metabolomics