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

ABSTRACT

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.