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Fatty Acid Synthase

Fatty acid synthase (FASN) is a homodimeric protein; each monomer is a large polypeptide comprised of six separate enzymatic domains working in concert to synthesize the 16-carbon saturated fatty acid palmitate from building blocks of acetyl-CoA and malonyl-CoA. FASN also can localize to intracellular membranes; the specific impact of this partitioning on the cell’s function remains a field of active exploration. FASN can be phosphorylated by kinases such as mammalian target of rapamycin (mTOR) and human epidermal growth factor receptor 2 (Her2) and this regulation may be important for both activity of the enzyme and its subcellular localization. The FASN enzyme may be regulated by protein-protein interactions. FASN has been shown to co-localize with caveolin-1 on the membranes of prostate cancer cells; the presence of these antigens correlates with poor prognosis, notwithstanding that the functionality of this co-localization has not been elucidated. FASN has been shown to interact physically with the protein, designated as FAMIN, on perioxosomes, driving the flux of lipid synthesis; and the thyroid hormone responsive protein Spot14 has been shown to enhance the activity of the FASN enzyme. This enzyme and de novo lipogenesis (DNL), its cognate pathway, are critical components of tumor cell survival and proliferation for a wide range of cancers.

References

1.Buckley D, et al. Pharmacol Ther. 2017;177:23–31.

Metabolic Enzyme/Protease

11β-HSD(15) 15-PGDH(1) ACC(10) ACE(9) AChE(29) Adenylate Cyclase(10) ALDH(14) Aldose Reductase(5) Aminopeptidase(17) BACE(18) Casein Kinase(41) CAT(5) Cathepsin(8) CETP(10) COMT(2) CPG2(1) CYPs(6) Decarboxylase(3) Dehydrogenase(87) DGAT(4) Dopamine beta-hydroxylase(2) DPP(28) Elastase(6) FAAH(19) Factor Xa(22) Fatty Acid Synthase(16) Ftase(2) FXR(22) Glucokinase(1) GSNOR(2) Guanylate Cyclase(9) HMGCR(17) IDH(7) IDO(20) IMPDH(2) LDH(2) LDL(5) Lipase(13) Lipid(9) MAGL(3) MAO(51) MMP(48) NAMPT(7) Neprilysin(6) Other Targets(9) P450(87) PAI-1(7) Phosphatase(49) Phospholipase(43) PPAR(86) Protein Phosphatase/PTP(6) Renin(7) Retinoid Receptor(23) SCD(6) Steroid Sulfatase (STS)(2) Thioredoxin(1) TPH(5) Transferase(24) Vitamin(39) Xanthine Oxidase (XAO)(6)