Alterations in Circulating Amino Acid Metabolite Ratio Associated with Arginase Activity Are Potential Indicators of Metabolic Syndrome: The Korean Genome and Epidemiology Study

Upregulated arginase activity, which competes with nitric oxide synthase (NOS), impairs nitric oxide production and has been implicated in various metabolic disorders. This study examined whether circulating amino acid metabolite ratios are associated with arginase and NOS activities and whether arginine bioavailability is associated with metabolic syndrome (MetS). Data related to arginase and NOS activities were collected from non-diabetic Koreans without cardiovascular disease (n = 1998) in the Ansan-Ansung cohorts (2005-2006). Subsequently, correlation and multivariate logistic regression analyses were performed. With the increase in the number of MetS risk factors, ratios of circulating amino acid metabolites, such as those of ornithine/citrulline, proline/citrulline, and ornithine/arginine, also significantly increased, whereas arginine bioavailability significantly decreased. These metabolite ratios and arginase bioavailability were also significantly correlated with MetS risk-related parameters, which remained significant after adjusting for covariates. In addition, logistic regression analysis revealed that high ratios of circulating metabolites and low arginine bioavailability, which indicated increased arginase activity, were significantly associated with a high MetS risk. This study demonstrated that altered ratios of circulating amino acid metabolites indicates increased arginase activity and decreased arginine bioavailability, both of which can be potential markers for MetS risk.