When do Lasses (longevity assurance genes) become CerS (ceramide synthases)?: Insights into the regulation of ceramide synthesis.

Ceramide is the key intermediate in the pathway of sphingolipid (SL) biosynthesis (1) and an important intracellular signaling molecule (2,3). Ceramide consists of a sphingoid long chain base to which a fatty acid is attached via an amide bond (Fig. 1). When the chemical composition of SLs was first determined in the 1940s (4), stearic acid (C18:0) was identified as the major fatty acid attached to the sphingoid base. Later, with the development of more sensitive techniques (5,6), it became clear that mammalian SLs contain a wide variety of fatty acids, ranging in length from C14-C32 that are predominantly saturated, and can contain αor ω-hydroxyl groups (7,8). Within the past few years, there has been renewed interest in the functional significance of this fatty acid variability, and this mini-review will focus on current advances in our understanding of how the fatty acid composition of ceramide is regulated. In particular, we will discuss a