Fig. 4. Inhibitors of fatty acid synthesis.

Fatty acid synthesis can be used along with exogenous fatty acids for lipid production, which can be used to produce membranes and lipid droplets and to modulate signalling pathways. Mitochondrial acetyl-CoA derived from fatty acid oxidation (which can be an important tricarboxylic acid (TCA) cycle carbon source in some cancers), glucose or other sources can condense with oxaloacetate (OAA) to form citrate, which can then be exported from the mitochondrion. Citrate and acetate — via ATP citrate lyase (ACLY) and synthetase short-chain family member 2 (ACSS2), respectively — are two major sources of cytoplasmic acetyl-CoA, from which acetyl-CoA carboxylase (ACC1 and ACC2) makes malonyl-CoA, which is then cyclically extended by the addition of carbons from acetyl-CoA by fatty acid synthase (FASN) to make saturated fatty acids. Fatty acids are desaturated by stearoyl-CoA desaturase 1 (SCD1). Membrane desaturation has a key role in maintaining membrane fluidity. Fatty acid catabolism is initiated with the formation of fatty acyl-CoA by an acyl-CoA ligase. Fatty acyl-CoA is converted by carnitine palmitoyltransferase 1 (CPT1) to an acylcarnitine, which is then imported into the mitochondrion via carnitine–acylcarnitine translocase (CAT, SLC25A20). Inside the mitochondrion, CPT2 converts the acyl-carnitine back to a fatty acyl-CoA, which can then be cyclically oxidized to two carbon acetyl-CoA molecules. Inhibitors of key enzymes or transporters are shown (blue). aKG, α-ketoglutarate; CoA, Coenzyme A; CTP, citrate transporter protein (SLC25A1); PDH, pyruvate dehydrogenase.