Fatty Acid and Lipid Metabolism Antibody Sampler Kit II #99729

Sterol regulatory element–binding proteins (SREBPs) are basic helix-loop-helix–leucine zipper (bHLH-Zip) transcription factors (1,2). Studies show that SREBP-1-dependent fatty acid homeostasis has a critical role in promoting the pro-tumor phenotype of M2-like tumor-associated macrophages (TAMs), and inhibition of SREBP-1 enhances the efficacy of immune checkpoint blockade (3). In addition, statin-induced suppression of cholesterol biosynthesis stimulates SREBP-1 activation and, consequently, induces TGF-β signaling, promoting the epithelial-to-mesenchymal transition in pancreatic ductal adenocarcinoma (4).

ATP-citrate lyase (ACL) is a homotetramer that catalyzes the formation of acetyl-coenzyme A (CoA) and oxaloacetate (OAA) in the cytosol, which is the key step for the biosynthesis of fatty acids, cholesterol, and acetylcholine, as well as for gluconeogenesis (5). Phosphorylation of ACL at Ser455 abolishes the homotropic allosteric regulation by citrate and enhances the catalytic activity of the enzyme (6).

Fatty acid synthase (FASN) catalyzes the synthesis of long-chain fatty acids from acetyl-CoA and malonyl-CoA. FASN is active as a homodimer with seven different catalytic activities and produces lipids in the liver for export to metabolically active tissues or storage in adipose tissue (7).

Acetyl-CoA carboxylase (ACC) catalyzes the pivotal step of the fatty acid synthesis pathway. Phosphorylation by AMPK at Ser79 or by PKA at Ser1200 inhibits the enzymatic activity of ACC (8).

Stearoyl-CoA desaturase 1 (SCD1) is a key lipogenic enzyme found in the endoplasmic reticulum that catalyzes the conversion of palmitoyl–CoA and stearoyl–CoA to palmitoleoyl–CoA (16:1) and oleoyl–CoA (18:1) (1-3). Palmitoleate and oleate are the major components of triglycerides, membrane phospholipids, and cholesterol esters (9).

Diacylglycerol O-acyltransferase 1 (DGAT1) catalyzes triacylglycerol biosynthesis from diacylglycerol and fatty acyl-CoA (10). Studies show that DGAT1 is highly expressed in glioblastoma (GBM), stimulating the storage of excess fatty acids in triacylglycerols and lipid droplets to block GBM cells from oxidative damage. DGAT1 inhibition in GBM cells enhances reactive oxygen species (ROS) production and causes mitochondrial damage, leading to cancer cell death (11). In addition, Jumonji domain-containing 6 (JMJD6) is critical for clear cell renal cell carcinoma (ccRCC) development. JMJD6, along with RBM39, promotes DGAT1 expression. DGAT1 inhibition suppresses ccRCC tumorigenesis in vivo (12).

Acyl-CoA synthetase long-chain family member 4 (ACSL4) preferentially catalyzes the formation of arachidonoyl-CoA (AA-CoA) by inserting CoA into arachidonic acid (AA) (13). ACSL4-catalyzed acyl-CoAs also participate in the regulation of steroidogenesis (14), eicosanoid biosynthesis (15), and phospholipid remodeling (16). ACSL4 is an essential enzyme for the conversion of two key ferroptosis-inducing signals, oxidized arachidonic and adrenic phosphatidylethanolamines (17,18). Genome-wide CRISPR/Cas9-based genetic screens have demonstrated that ACSL4 is an essential component for ferroptosis execution (18), and genetic or pharmacological inhibition of ACSL4 can initiate a specific anti-ferroptotic rescue pathway (17). ACSL4 expression is upregulated in ferroptosis-sensitive cancer cells compared with ferroptosis-resistant cells (19). It has been shown to predict sensitivity to ferroptosis in a panel of basal-like breast cancer cell lines (18). Moreover, high ACSL4 protein expression in hepatocellular carcinoma (HCC) clinical tissue specimens is associated with improved patient outcomes after sorafenib treatment and could serve as a predictive biomarker (20).