Unraveling the Cyclization of l-Argininosuccinic Acid in Biological Samples: A Study via Mass Spectrometry and NMR Spectroscopy

Abstract

Since l-argininosuccinic acid (ASA) is the characteristic biomarker for the diagnosis of certain diseases, its reliable detection in complex biological samples is necessary to obtain a complete evaluation with greater specificity and accuracy. ASA can undergo intramolecular cyclization, yielding an equilibrium with the resulting cyclic forms, which can predominate under different analytical conditions. In this work, the appearance and transformation of the different forms of ASA have been studied and a strategy for targeted screening analysis of ASA and its cyclic forms using capillary electrophoresis-electrospray ionization-time-of-flight mass spectrometry (CE-ESI-TOF-MS) has been developed. The data and spectra obtained allowed us to gain further insight into accurate identification, concluding that there is a dynamic equilibrium depending on the pH. Moreover, one- and two-dimensional NMR spectroscopy experiments have allowed us to determine the predominant tautomeric structure for the major cyclic ASA derivative, confirming the importance of intramolecular hydrogen bonds.

Microwave Radiation Caused Dynamic Metabolic Fluctuations in the Mammalian Hippocampus

“…Its precursors are aspartic acid and citrulline, which are subsequently decomposed into arginine and fumaric acid. The loss of activity of related enzymes leads to an abnormal content of argininosuccinic acid in body fluids, cells, or tissues [23]. Argininosuccinic acid metabolism is closely related to cognition, and the loss of argininosuccinic acid synthase leads to the harmful accumulation of ammonia in the blood and cerebrospinal fluid and impairs brain function [24,25].…”

Profiling of polar ionogenic metabolites in Polish wines by capillary electrophoresis‐mass spectrometry

“…Interestingly, cyclic argininosuccinic acid was found to be one of the metabolites responsible for the classification of the two sets of wine samples, expressed more in white wines. This compound is found in a dynamic equilibrium with argininosuccinic acid in its open form; at an acidic pH as is the case in wines, cyclic argininosuccinic acid predominates [ 21 ].…”