Issue 34, 2014

A study on the chiral inversion of mandelic acid in humans

Abstract

Mandelic acid is a chiral metabolite of the industrial pollutant styrene and is used in chemical skin peels, as a urinary antiseptic and as a component of other medicines. In humans, S-mandelic acid undergoes rapid chiral inversion to R-mandelic acid by an undefined pathway but it has been proposed to proceed via the acyl-CoA esters, S- and R-2-hydroxy-2-phenylacetyl-CoA, in an analogous pathway to that for Ibuprofen. This study investigates chiral inversion of mandelic acid using purified human recombinant enzymes known to be involved in the Ibuprofen chiral inversion pathway. Both S- and R-2-hydroxy-2-phenylacetyl-CoA were hydrolysed to mandelic acid by human acyl-CoA thioesterase-1 and -2 (ACOT1 and ACOT2), consistent with a possible role in the chiral inversion pathway. However, human α-methylacyl-CoA racemase (AMACR; P504S) was not able to catalyse exchange of the α-proton of S- and R-2-hydroxy-2-phenylacetyl-CoA, a requirement for chiral inversion. Both S- and R-2-phenylpropanoyl-CoA were epimerised by AMACR, showing that it is the presence of the hydroxy group that prevents epimerisation of R- and S-2-hydroxy-2-phenylacetyl-CoAs. The results show that it is unlikely that 2-hydroxy-2-phenylacetyl-CoA is an intermediate in the chiral inversion of mandelic acid, and that the chiral inversion of mandelic acid is via a different pathway to that of Ibuprofen and related drugs.

Graphical abstract: A study on the chiral inversion of mandelic acid in humans

Supplementary files

Article information

Article type
Paper
Submitted
16 Dec 2013
Accepted
10 Jul 2014
First published
10 Jul 2014

Org. Biomol. Chem., 2014,12, 6737-6744

Author version available

A study on the chiral inversion of mandelic acid in humans

M. Yevglevskis, C. R. Bowskill, C. C. Y. Chan, J. H.-J. Heng, M. D. Threadgill, T. J. Woodman and M. D. Lloyd, Org. Biomol. Chem., 2014, 12, 6737 DOI: 10.1039/C3OB42515K

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