Interactions of anti-inflammatory 2-arylpropionates (profens) with the metabolism of fatty acids: in vitro studies.

This review shows conclusively that profens can enter physiological pathways of lipid biochemistry. The first step in this interaction is the formation of an acyl-CoA thioester. These conjugates can lead to the incorporation of the xenobiotic acid into lipids. The resulting hybrid triglycerides have the potential to form long-lasting residues in adipose tissues and to be incorporated into membranes. Furthermore, the acyl-CoA conjugate may also alter lipid biochemistry by inhibiting lipid beta-oxidation either by interfering with the acyl-CoA synthetases or by modifying CoA levels. Thus, the acyl-CoA conjugates of profens intermediates in the inversion of inactive (R)-profens to active (S)-profens can be viewed as pivotal to bioactivation and to pathways of potential toxicity.