Stearoyl-CoA desaturase isoforms 3 and 4: Avenues for tissue-specific δ9 desaturase activity

Abstract

The stearoyl-CoA desaturase (SCD) family of enzymes catalyzes the rate-limiting step in the synthesis of monounsaturated fatty acids (MUFAs). Four SCD isoforms have been identified in mouse (SCD1-4). While the involvement of SCD1 in metabolic disease has been well investigated, SCD3 and SCD4 remain largely unexplored. Preliminary studies in mouse models reveal that SCD3 and SCD4 exhibit unique tissue expression patterns compared to SCD1 and SCD2. Scd3 is expressed in the harderian gland, preputial gland, and skin, while Scd4 is mainly expressed in the heart. The limited tissue expression of these isoforms likely stems from the combinatorial presence of different regulatory elements. In fact, early work on SCD3 and SCD4 has revealed several distinct factors that modulate expression of these genes. Notably, while leptin represses Scd1 in the liver, Scd4 is the only isoform repressed by leptin in the heart. SCD3 also demonstrates unique substrate specificity, despite sharing 88 % protein homology with SCD1. SCD3 preferentially desaturates palmitate, 16:0, to yield palmitoleate, 16:1(n-7). This review summarizes the preliminary work on the two most recently discovered SCD isoforms and highlights the motivations for further studies of these unique δ9 desaturase enzymes.