The role of sphingolipids in drug metabolism and transport

Introduction: Sphingolipids represent a diverse class of lipid molecules. In addition to their function as membrane structural components, they serve as signaling molecules involved in various biological processes such as cell metabolism, growth, differentiation, stress and inflammatory responses and apoptosis. Sphingolipids may modulate the activity and/or expression of cytochrome P450s (CYPs) and transporters, which suggests that they may affect drug metabolism and excretion. Areas covered: In this review, the authors provide an overview of the properties of sphingolipid structures and metabolism. They also describe the effects of sphingolipids on the activity and expression of CYPs and transporters. In addition, the authors discuss the pathologic conditions where the sphingolipid metabolism is dysregulated particularly in association with inflammation and cancer. Expert opinion: Sphingolipidomic approaches have become accessible with the aid of advances in analytical technology. Sphingolipid profiles are modified by diseases, genetic disorders or certain drug treatment. The consequent changes in sphingolipid contents may alter the activities of detoxifying enzymes and those associated with cell viability. Since CYPs and transporters play roles in xenobiotics metabolism and excretion, sphingolipidomic information may be of use in understanding drug effect and toxicity.