Fatty acid desaturase 2 (Delta-6 desaturase) (FADS2)

Fatty acid desaturase 2 (FADS2), commonly known as Delta-6 desaturase (D6D), is a membrane-bound enzyme that serves as the rate-limiting step in the biosynthesis of long-chain polyunsaturated fatty acids (PUFAs) (UniProt, Wikipedia). It catalyzes the conversion of the essential fatty acids linoleic acid (LA) and alpha-linolenic acid (ALA) into gamma-linolenic acid (GLA) and stearidonic acid (SDA), respectively (NIH, PubMed). This enzymatic activity is crucial for the eventual production of arachidonic acid (AA), which acts as a precursor for various pro-inflammatory eicosanoids like prostaglandins and leukotrienes (NIH). Dysregulation of D6D activity is linked to a wide range of conditions, including metabolic syndrome, type 2 diabetes, cardiovascular disease, and several types of cancer (MDPI, AHA Journals). In many inflammatory and neoplastic diseases, D6D activity is significantly upregulated, making it an attractive therapeutic target (NIH). Experimental inhibitors such as SC-26196 have demonstrated the ability to reduce inflammation and impede tumor growth in animal models by depleting cellular AA levels (PubMed). However, because D6D also plays a role in skin health through the synthesis of sapienic acid and maintains overall lipid homeostasis, its systemic inhibition presents potential safety challenges (UniProt, NIH). Furthermore, some studies suggest that D6D inhibition might influence muscle protein turnover, potentially increasing protein degradation (NIH).

Other names

Delta-6 desaturaseD6DAcyl-CoA 6-desaturaseDES6FADSD6Linoleoyl-CoA desaturaseLLCDL2

Inhibition of the rate-limiting desaturation of linoleic acid and alpha-linolenic acid, reducing the production of arachidonic acid and pro-inflammatory eicosanoids.