cryo-EM analysis, where ACP is observed bound to the various catalytic domains in the barrel-shaped yeast fatty acid synthase. The cryo-EM results suggest that the binding of ACP to various sites is asymmetric and stochastic, as also indicated by computer-simulation studies Regulation Metabolism and homeostasis of fatty acid synthase is transcriptionally regulated by Upstream Stimulatory Factors (USF1 and USF2) and sterol regulatory element binding protein-1c (SREBP-1c) in response to feeding/insulin in living animals. Although liver X receptors (LXRs) modulate the expression of sterol regulatory element binding protein-1c (SREBP-1c) in feeding, regulation of FAS by SREBP-1c is USF-dependent. Acylphloroglucinols isolated from the fern Dryopteris crassirhizoma show a fatty acid synthase inhibitory activity. Clinical significance The gene that codes for FAS has been investigated as a possible oncogene. FAS is upregulated in breast and gastric cancers, as well as being an indicator of poor prognosis, and so may be worthwhile as a chemotherapeutic target. FAS inhibitors are therefore an active area of drug discovery research. FAS may also be involved in the production of an endogenous ligand for the nuclear receptor PPARalpha, the target of the fibrate drugs for hyperlipidemia, and is being investigated as a possible drug target for treating the metabolic syndrome. Orlistat which is a gastrointestinal lipase inhibitor also inhibits FAS and has a potential as a medicine for cancer. In some cancer cell lines, this protein has been found to be fused with estrogen receptor alpha (ER-alpha), in which the N-terminus of FAS is fused in-frame with the C-terminus of ER-alpha. An association with uterine leiomyomata has been reported. See also Discovery and development of gastrointestinal lipase inhibitors Fatty acid synthesis Fatty acid metabolism Fatty acid degradation Enoyl-acyl carrier protein reductase List of fatty acid metabolism disorders References Further reading External links Fatty Acid Synthesis: Rensselaer Polytechnic Institute Fatty Acid Synthase: RCSB PDB Molecule of the Month 3D electron microscopy structures of fatty acid synthase from the EM Data Bank(EMDB) PDBe-KB provides an overview of all the structure information available in the PDB for Human Fatty acid synthase Transferases EC 2.3.1 Metabolism Fatty acids NADPH-dependent enzymes Enzymes of known structure