Study on the metabolic mechanism of chiral inversion of S-Mandelic acid in vitro

Mandelic acid (MA) is generally used as a biological indicator of occupational exposure to styrene, which is classified as a class of hazardous environmental pollutants. It was found to undergo one‐directional chiral inversion (S‐MA to R‐MA) in Wistar and Sprague‐Dawley rats in vivo. This study was aimed to explore the metabolic mechanism of chiral inversion of S‐MA in vitro. S‐MA was converted to R‐MA in rat hepatocytes, whereas MA enantiomers remained unchanged in acidic and neutral phosphate buffers, HepG2 cells, and intestinal flora. In addition, the synthesized S‐MA‐CoA thioester was rapidly racemized and hydrolyzed to R‐MA by rat liver homogenate and S9, cytosolic and mitochondrial fractions. The data suggest that chiral inversion of S‐MA may involve the hydrolysis of S‐MA‐CoA, and its metabolic mechanism could be the same as that of 2‐arylpropionic acid (2‐APA) drugs. Chirality 24:86–95, 2012. © 2011 Wiley Periodicals, Inc.