FASN

Official Full Name

fatty acid synthase

Organism

Homo sapiens

GeneID

2194

Background

The enzyme encoded by this gene is a multifunctional protein. Its main function is to catalyze the synthesis of palmitate from acetyl-CoA and malonyl-CoA, in the presence of NADPH, into long-chain saturated fatty acids. 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. [provided by RefSeq, Jul 2008]

Synonyms

FAS; OA-519; SDR27X1;

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Detailed Information

Fatty acid synthase (FASN) is a key enzyme that polymerizes small molecular carbon units into long-chain fatty acids in the process of fatty acid biosynthesis. It can regulate the synthesis of endogenous fatty acids. Its main product is palmitic acid and is stored in the form of triglycerides. Energy is mainly involved in phospholipid synthesis, cell membrane structure, lung surface active substance production, intracellular signal transduction, and protein acylation. Numerous studies have shown that FASN is not expressed or only slightly expressed in most normal tissues, while its expression is significantly up-regulated in a variety of malignant tumor tissues. FASN-mediated abnormal substance metabolism plays an important role in the occurrence and development of tumors.

Characteristics of FASN

The human FASN gene is located on chromosome 17q25. It is produced by 7512 nucleotides encoding 2504 amino acids. It is a dimer composed of two peptide chains with a molecular weight of 270KD. It has a variety of catalytic functions and is connected in a head-to-tail manner. The formation of a catalytic center includes N-terminal β-keto acyl synthesis, acetyl/malonyl monoacyl transfer and dehydration domains, and C-terminal enol reduction, β-keto acyl reduction domain, acyl carrier protein and thioester domains. The acetyl/malonyl transfer region is involved in the substrate reaction, the β-ketoester acyl synthesis region is produced in the synthesis reaction, and the thioester region is involved in the carbon chain termination reaction.

Catalytic Activity of FASN

The main product of FASN is palmitic acid, which stores energy in the form of triglycerides, and participates in the synthesis of phospholipids, cell membrane structure and lung surface active substances, the transformation of intracellular signals, and the acylation of proteins. FASN is the most important enzyme for the synthesis of endogenous fatty acids in higher animals. It is a macromolecular protein complex with 7 enzymatic activities including condensation, transacylation, reduction, and dehydration. Active FASN is formed by two identical subunits connected end to end. The subunits depolymerize and the enzyme activity is lost. The peptide chain of each subunit consists of three domains: domain I is the unit for the substrate to enter the condensation reaction, domain II is the unit for the reduction reaction, and domain III is the unit for the release of synthetic products. In the presence of NADPH, FASN adds two carbon atoms to acetyl CoA and propionyl CoA to synthesize long-chain fatty acids.

Fig1 The process of mammalian fatty acid synthesis

FASN and Tumor

FASN expression is significantly up-regulated in a variety of tumor tissues. A large number of studies speculate that the possible mechanism is that in normal cell fat synthesis, the regulation of FASN expression by carbohydrates and exogenous fatty acids is mainly mediated by hormones. These hormones can stimulate (such as insulin, glucocorticoids, etc.) or inhibit (such as glucagon, cAMP, etc.) FASN fat synthesis; and in the fat synthesis of tumor cells, FASN does not seem to be sensitive to hormone signals. The high expression of FASN in tumor cells is mainly achieved by regulating the expression of the transcription factor SREBP1c. The expression of SREBP1c is caused by abnormal growth factors (GF) and growth factor receptors (GFR) and/or steroid hormones (SH). The activation of steroid hormone receptor (SHR)-mediated signaling pathway, zero Akt can stimulate the synthesis and nuclear accumulation of activated SREBP1c; and SH self can directly increase the expression of FASN by up-regulating the proteolytic activity of SREBP1c.

References:

Smith, S., Witkowski, A., & Joshi, A. K. (2003). 'Structural and functional organization of the animal fatty acid synthase.' Progress in lipid research, 42(4), 289–317.
Smith, & S. (1994). 'The animal fatty acid synthase: one gene, one polypeptide, seven enzymes.'Faseb Journal Official Publication of the Federation of American Societies for Experimental Biology, 8(15), 1248-1259.
Weiss, L. , Hoffmann, G. E. , Schreiber, R. , Andres, H. , Fuchs, E. , & E Körber, et al. (2009). 'Fatty-acid biosynthesis in man, a pathway of minor importance. purification, optimal assay conditions, and organ distribution of fatty-acid synthase : biological chemistry hoppe-seyler.' Biological Chemistry, 367.

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