Stearoyl-CoA desaturase in development and disease

The conversion of straight chain saturated fatty acids to their bent, unsaturated counterparts significantly increases their structural and functional complexity. Desaturation of fatty acids, where double bonds are introduced is an enzymatic reaction. Exploring 56 eukaryotic genomes, 275 desaturase homologs have been identified. Membrane-bound desaturases are the dominant form and are ubiquitous in bacteria and eukaryotes. Four subfamilies of desaturases introduce double bonds at distinct locations. Among them, the First Desaturase subfamily introduces the first double bond among which the stearoyl-CoA desaturases (SCDs) are the most predominant. SCD is a rate-limiting enzyme that generates monounsaturated fatty acids (MUFA) from saturated fatty acids (SFA) at the endoplasmic reticulum membrane, where SCD is localized. The MUFAs are utilized to produce a variety of cell membrane components including triglycerides, phospholipids, and cholesterol esters which play important roles in membrane fluidity, organelle function, and signal transduction. SCD activity is a critical regulator of SFA to MUFA ratio and, therefore, of overall cell function, growth, and survival. In this review, we will provide the latest updates on the expected as well as unanticipated roles of SCD in development, metabolism and disease with a focus on cancer and the central nervous system.