A sportomics soccer investigation unveils an exercise-induced shift in tyrosine metabolism leading to hawkinsinuria

Thássia Casado Lima França; Renan Muniz-Santos; Luiz Carlos Caetano; Gustavo H M F Souza; Henrique Fonseca Goulart; Marcio Assis; Altamiro Bottino; Adriana Bassini; Antonio Euzébio Goulart Santana; Eduardo Seixas Prado; L C Cameron

doi:10.3389/fnut.2023.1169188

A sportomics soccer investigation unveils an exercise-induced shift in tyrosine metabolism leading to hawkinsinuria

Front Nutr. 2023 Jun 13:10:1169188. doi: 10.3389/fnut.2023.1169188. eCollection 2023.

Affiliations

¹ Laboratory for Research in Physical Exercise and Metabolism, Federal University of Alagoas, Maceió, Alagoas, Brazil.
² Laboratory of Protein Biochemistry, Federal University of State of Rio de Janeiro, Rio de Janeiro, Brazil.
³ Institute of Chemistry and Biotechnology, Federal University of Alagoas, Maceió, Alagoas, Brazil.
⁴ MS Applications and Development Laboratory, Waters Corporation, São Paulo, Brazil.
⁵ Research Laboratory on Natural Resources, Federal University of Alagoas, Maceió, Alagoas, Brazil.
⁶ Youth Soccer Teams, Fluminense Football Club, Rio de Janeiro, Brazil.
⁷ Health and Performance Center/Soccer Professional Team, Sociedade Esportiva Palmeiras, São Paulo, Brazil.

Abstract

Tyrosine metabolism has an intense role in the synthesis of neurotransmitters. Our study used an untargeted, sportomics-based analysis of urine samples to investigate changes in metabolism during a soccer match in 30 male junior professional soccer players. Samples were collected before and after the match and analyzed using liquid chromatography and mass spectrometry. Results showed significant changes in tyrosine metabolism. Exercise caused a downregulation of the homogentisate metabolites 4-maleylacetoacetate and succinylacetone to 20% (p = 4.69E-5) and 16% (p = 4.25E-14), respectively. 4-Hydroxyphenylpyruvate, a homogentisate precursor, was found to be upregulated by 26% (p = 7.20E-3). The concentration of hawkinsin and its metabolite 4-hydroxycyclohexyl acetate increased ~six-fold (p = 1.49E-6 and p = 9.81E-6, respectively). Different DOPA metabolism pathways were also affected by exercise. DOPA and dopaquinone increased four-to six-fold (p = 5.62E-14 and p = 4.98E-13, respectively). 3-Methoxytyrosine, indole-5,6-quinone, and melanin were downregulated from 1 to 25%, as were dopamine and tyramine (decreasing to up to 5% or 80%; p= 5.62E-14 and p = 2.47E-2, respectively). Blood TCO₂ decreased as well as urinary glutathione and glutamate (40% and 10% respectively) associated with a two-fold increase in pyroglutamate. Our study found unexpected similarities between exercise-induced changes in metabolism and the inherited disorder Hawkinsinuria, suggesting a possible transient condition called exercise-induced hawkinsinuria (EIh). Additionally, our research suggests changes in DOPA pathways may be involved. Our findings suggest that soccer exercise could be used as a model to search for potential countermeasures in Hawkinsinuria and other tyrosine metabolism disorders.

Keywords: amino acids metabolism; biochemistry of exercise; exercise metabolome; metabolic pathways; metabolomics; neurometabolism; sports science.