Enzymes of sphingolipid metabolism: From modular to integrative signaling

Many enzymes of sphingolipid metabolism are regulated in response to extra- and intracellular stimuli and in turn serve as regulators of levels of bio active lipids (such as sphingosine, ceramide, sphingosine l-phosphate, and diacylglycerol), and as such, they serve a prototypical modular function in cell regulation. However, lipid metabolism is also closely interconnected in that a product of one enzyme serves as a substrate for another. Moreover , many cell stimuli regulate more than one of these enzymes, thus adding to the complexity of regulation of lipid metabolism. In this paper, we review the status of enzymes of sphingolipid metabolism in cell regulation and pr opose a role for these enzymes in integration of cell responses, a role tha t builds on the modular organization while also taking advantage of the com plexity and interconnectedness of lipid metabolism, thus providing for a co mbinatorial mechanism of generating diversity in cell responses. This may b e a general prototype for the involvement of metabolic pathways in cell reg ulation.