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Metabolome-wide association study of phenylalanine in plasma of common marmosets

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Abstract

Little systematic knowledge exists concerning the impacts of cumulative lifelong exposure, termed the exposome, on requirements for nutrients. Phenylalanine (Phe) is an essential dietary amino acid with an aromatic ring structure similar to endogenous metabolites, dietary compounds and environmental agents. Excess plasma Phe in genetic disease or nutritional deficiency of Phe has adverse health consequences. In principle, structurally similar chemicals interfering with Phe utilization could alter Phe requirement at an individual level. As a strategy to identify components of the exposome that could interfere with Phe utilization, we tested for metabolites correlating with Phe concentration in plasma of a non-human primate species, common marmosets (Callithrix jacchus). The results of tests for more than 5,000 chemical features detected by high-resolution metabolomics showed 17 positive correlations with Phe metabolites and other amino acids. Positive and negative correlations were also observed for 33 other chemicals, which included matches to endogenous metabolites and dietary, microbial and environmental chemicals in database searches. Chemical similarity analysis showed many of the matches had high structural similarity to Phe. Together, the results show that chemicals in marmoset plasma could impact Phe utilization. Such chemicals could contribute to early lifecycle developmental disorders when neurological development is vulnerable to Phe levels.

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Abbreviations

CAS:

Chemical abstracts service

CID:

PubChem compound ID

FDR:

False discovery

KEGG:

Kyoto encyclopedia of genes and genomes

LC–MS:

Liquid chromatography–mass spectrometry

m/z :

mass to charge

MWAS:

Metabolome-wide association study

Phe:

Phenylalanine

PPAR-γ:

Peroxisome proliferator-activated receptor-γ

RT:

Retention time

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Acknowledgments

The authors gratefully acknowledge the technical expertise of Yongliang Liang and ViLinh Tran for mass spectrometry analyses. This study was supported by NIH grants, AG038746 (D.J., D. P., L.W.), ES023485 (D.J, Y.G.), ES009047 (D.J.), HL113451 (D.J.) and ES019776 (D.J.).

Conflict of interest

Authors have no conflicts of interest.

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Author notes

  1. Quinlyn A. Soltow

    Present address: ClinMet Inc., 3210 Merryfield Row, San Diego, CA, 92121, USA

Authors and Affiliations

  1. Clinical Biomarkers Laboratory, Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University, 205 Whitehead Research Center, Atlanta, GA, 30322, USA

    Young-Mi Go, Douglas I. Walker, Quinlyn A. Soltow, Karan Uppal & Dean P. Jones

  2. Chemistry Department, Emory University, Atlanta, GA, 30322, USA

    Fredrick H. Strobel

  3. Department of Civil and Environmental Engineering, Tufts University, Medford, MA, 02155, USA

    Douglas I. Walker & Kurt Pennell

  4. New England Primate Research Center, Harvard University, Southborough, MA, 01772, USA

    Lynn M. Wachtman

  5. University of Washington, Seattle, WA, 98195, USA

    Daniel E. L. Promislow

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  1. Young-Mi Go
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Correspondence to Dean P. Jones.

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Go, YM., Walker, D.I., Soltow, Q.A. et al. Metabolome-wide association study of phenylalanine in plasma of common marmosets. Amino Acids 47, 589–601 (2015). https://doi.org/10.1007/s00726-014-1893-x

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  • DOI: https://doi.org/10.1007/s00726-014-1893-x

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