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

Albrecht E, Waldenberger M, Krumsiek J, et al. Metabolite profiling reveals new insights into the regulation of serum urate in humans. Metabolomics. 2013;10(1):141-151.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

Hormonal aspects of human gout--excretion of adrenal hormone derivatives in gouty patients.

Forty-seven patients with gout, 28 of whom had not previously been treated with allopurinol, and 25 normal subjects, were examined for 24-h urinary excretion of the most important adrenal steroid derivatives. Results were submitted to statistical analysis and several variables have been taken in consideration. The untreated patients showed significantly higher values of uricemia, urinary uric acid, triglycerides, slightly higher values of androsterone, 11-oxo-androsterone + 11-oxo-etiocholanolone, dehydroepiandrosterone, and slightly lower values of 11-hydroxyandrosterone and pregnanetriol, in comparison to normal subjects. The different hormonal pattern seems to discriminate between patients with gout and normal subjects

Effect of fish oil supplementation on erythrocyte lipid pattern, malondialdehyde production and glutathione-peroxidase activity in psoriasis

Erythrocytes from psoriatic patients have a significant increase in polyunsaturated fatty acids (p less than 0.001) especially in arachidonic acid (p less than 0.001). Glutathione peroxidase activity, in both erythrocytes and platelets, was stimulated when compared with normal cells (p less than 0.001, less than 0.02, respectively) and the production of malondialdehyde was also increased in psoriasis (p less than 0.01). The level of plasma selenium was significantly reduced (52.80 vs 72.49 ng/ml; p less than 0.001). alpha-Tocopherol and retinol were both normal in plasma of psoriatics. After two months of fish oil supplementation, the erythrocyte lipid pattern was changed, eicosapentaenoic and dochesaenoic acids substituting the arachidonate in the membrane. A reduction in malondialdehyde (p less than 0.01), a prolongation of bleeding time (p less than 0.05) and a further stimulation of glutathione-peroxidase (p less than 0.001) in both erythrocytes and platelets was also found