Metabolite profiling reveals new insights into the regulation of serum urate in humans

Eva Albrecht, Melanie Waldenberger, Jan Krumsiek, Anne M. Evans, Ulli Jeratsch, Michaela Breier, Jerzy Adamski, Wolfgang Koenig, Sonja Zeilinger, Christiane Fuchs, Norman Klopp, Fabian J. Theis, H. Erich Wichmann, Karsten Suhre, Thomas Illig, Konstantin Strauch, Annette Peters, Christian Gieger, Gabi Kastenmüller, Angela DoeringChrista Meisinger

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Serum urate, the final breakdown product of purine metabolism, is causally involved in the pathogenesis of gout, and implicated in cardiovascular disease and type 2 diabetes. Serum urate levels highly differ between men and women; however the underlying biological processes in its regulation are still not completely understood and are assumed to result from a complex interplay between genetic, environmental and lifestyle factors. In order to describe the metabolic vicinity of serum urate, we analyzed 355 metabolites in 1,764 individuals of the population-based KORA F4 study and constructed a metabolite network around serum urate using Gaussian Graphical Modeling in a hypothesis-free approach. We subsequently investigated the effect of sex and urate lowering medication on all 38 metabolites assigned to the network. Within the resulting network three main clusters could be detected around urate, including the well-known pathway of purine metabolism, as well as several dipeptides, a group of essential amino acids, and a group of steroids. Of the 38 assigned metabolites, 25 showed strong differences between sexes. Association with uricostatic medication intake was not only confined to purine metabolism but seen for seven metabolites within the network. Our findings highlight pathways that are important in the regulation of serum urate and suggest that dipeptides, amino acids, and steroid hormones are playing a role in its regulation. The findings might have an impact on the development of specific targets in the treatment and prevention of hyperuricemia.

Original languageEnglish
Pages (from-to)141-151
Number of pages11
Issue number1
StatePublished - Feb 2014
Externally publishedYes


  • Allopurinol
  • Gaussian Graphical Modeling
  • Metabolite network
  • Pathway reconstruction
  • Purine metabolism
  • Uric acid


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