MSACL 2018 US Abstract

Topic: Metabolomics

Target Metabolomics Analysis Reveals Alteration in Pathways in 5p minus Patients by UPLC-MS/MS

Nilson Assuncao (Presenter)
UNIFESP

Bio: Graduated in Chemistry from the University of São Paulo (USP) - Institute of Chemistry of São Carlos, Master in Analytical Chemistry by the University of São Paulo (USP) - Institute of Chemistry of São Carlos and doctorate in Anal Chemistry by the University of São Paulo (USP) - Institute of Chemistry of São Carlos. Between 2006 and 2008 he was a postdoctoral fellow in the Department of Biochemistry of the Institute of Chemistry (USP). He held a post-doctorate at Scripps Institute California, San Diego in 2016-2017. He currently teaches at Unifesp's Chemical Biology and Translational Medicine postgraduate programs. In these programs my main line is bioanalytical applied to the study of Biomolecules. The projects within this line are related to the following topics: oxidative stress, metabolic errors, proteomics and bioanalytical applied to oncology and rare disease.

Authorship: Danielle Zildeana Sousa Furtado(1), Fernando Brunale Vilela de Moura Leite(1), Giuseppe Gianini Figueiredo Leite(1), Leticia Dias Lima Jedlicka(1,2), Etelvino José Henriques Bechara(2), Heron Dominguez Torres da Silva(1) and Nilson Antonio Assunção(1)
(1)Instituto de Ciências Ambientais, Químicas e Farmacêuticas, Universidade Federal de São Paulo (2)Instituto de Química, Universidade de São Paulo (3)Instituto de Estudos em Saúde Biológicas, Universidade Federal do Sul e Sudeste do Pará

Short Abstract

We analyzed urine and plasma samples from healthy and unhealthy people of both sexes aged 1–38 years old by UPLC-MS/MS. Student’s statistical test and metabolomic pathway analysis were applied. Increases in alanine, asparagine, aspartate, citrulline, glutamine, histidine, phenylalanine, leucine, methionine, serine, threonine, tyrosine, tryptophan, methionine sulfoxide, kyneurine, trans-4-hydroxyproline and sarcosine were found. In general, the catabolism of some metabolic pathways is affected in CDCS patients, primarily the TCA cycle; glycine, serine and threonine metabolism; histidine metabolism; phenylalanine metabolism and tryptophan metabolism. Furthermore, the disease has been shown to be related to the ageing process and folate deficiency.

Long Abstract

Introduction

Metabolomic analysis of urine can indicate some disturbances associated with inborn errors of amino acid metabolism, as metabolites are the end products of metabolic pathways. Therefore, the metabolomics profile was evaluated in patients with cri du chat syndrome (CDCS) to help unravel the biochemical changes that occur in this disease, which is characterized by a deletion located on the chromosome 5 short (-p) arm and has an incidence of 1/50,000 individuals worldwide.

Methods

Urine samples were collected from people of both sexes aged 1–38 years old; 36 samples were collected and analysed by ultra-performance liquid chromatography coupled to mass spectrometry. Student’s statistical test and metabolomic pathway analysis were applied to the data.

Results

Increases in alanine, asparagine, aspartate, citrulline, glutamine, histidine, phenylalanine, leucine, methionine, serine, threonine, tyrosine, tryptophan, methionine sulfoxide, kyneurine, trans-4-hydroxyproline and sarcosine were found. In general, the catabolism of some metabolic pathways is affected in CDCS patients, primarily the TCA cycle; glycine, serine and threonine metabolism; histidine metabolism; phenylalanine metabolism and tryptophan metabolism.

Conclusions & Discussion

The disease has been shown to be related to the ageing process and folate deficiency. These alterations in metabolites are associated with energy recuperation and glycolysis.


References & Acknowledgements:

1) E. Niebuhr, The Cri du Chat syndrome: epidemiology, cytogenetics, and clinical features, Hum. Genet. 44 (1978) 227–275.

2) D.Z.S. Furtado, F.B.V. de Moura Leite, C.N. Barreto, B. Faria, L.D.L. Jedlicka, E. de Jesus Silva, H.D.T. da Silva, E.J.H. Bechara, N.A. Assunção, Profiles of amino acids and biogenic amines in the plasma of Cri-du-Chat patients, J. Pharm. Biomed. Anal. 140 (2017) 137–145. doi:10.1016/j.jpba.2017.03.034

3) J. Lejeune, M.O. Rethoré, M. Peeters, M.C. de Blois, D. Rabier, P. Parvy, J. Bardet, P. Kamoun, [Cri-du-chat disease: plasma and urinary amino acids], Ann. Génétique. 33 (1990) 16–20.


Financial Disclosure

DescriptionY/NSource
GrantsyesFINEP
SalaryyesUNIFESP
Board Memberno
Stockno
Expensesno

IP Royalty: no

Planning to mention or discuss specific products or technology of the company(ies) listed above:

no