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

Ling-Bo Gao, Jin-Zhao Wang, Tong-Wei Yao, Su Zeng

Department of Pharmaceutical Analysis and Drug Metabolism, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

Chirality 2012 Jan

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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. Copyright © 2011 Wiley-Liss, Inc.

Citation

Ling-Bo Gao, Jin-Zhao Wang, Tong-Wei Yao, Su Zeng. Study on the metabolic mechanism of chiral inversion of S-mandelic acid in vitro. Chirality. 2012 Jan;24(1):86-95