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Fatty acid synthase [ edit ]
| Fatty acid synthase 脂肪酸合酶 | |||
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| Identifier | |||
| EC number | 2.3.1.85 | ||
| CAS number | 9045-77-6 | ||
| database | |||
| iNTENZ | IntEnz browsing | ||
| WITHIN | BRENDA entrance | ||
| ExPASy | NiceZyme browsing | ||
| KEGG | KEGG entrance | ||
| MetaCyc | Metabolic pathway | ||
| PRIAM | Overview | ||
| PDB | RCSB PDB PDBj PDBePDBsum | ||
| Gene ontology | AmiGO / EGO | ||
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| Fatty acid synthase 脂肪酸合酶 | |||||||||||
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PDB rendering based on 1xkt.
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| Identification | |||||||||||
| Code number | FASN ; FAS; OA-519; SDR27X1 | ||||||||||
| Extended ID | Genetics : 600212 Murine genes : 95485 Homologous genes : 55800 ChEMBL : 4158GeneCards : FASN Gene | ||||||||||
| EC number | 1.1.1.100 | ||||||||||
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| RNA Expression Pattern | |||||||||||
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| More expression data | |||||||||||
| Orthologs | |||||||||||
| Species | Humanity | Mice | |||||||||
| Come in | 2194 | 14104 | |||||||||
| Ensembl | ENSG00000169710 | ENSMUSG00000025153 | |||||||||
| UniProt | P49327 | P19096 | |||||||||
| mRNA sequence | NM_004104.4 | NM_007988.3 | |||||||||
| Protein sequence | NP_004095.4 | NP_032014.3 | |||||||||
| Gene position | Chr 17: 80.04 – 80.06 Mb | Chr 11: 120.81 – 120.82 Mb | |||||||||
| PubMedquery | [1] | [2] | |||||||||
Fatty acid synthase ( English: Fatty acid synthase ) is a multi-functional enzyme system, in mammals , its molecular weight up to 272 kDa . In the fatty acid synthase, the substrate and the intermediate molecule are transferred in each functional domain (which may be located in the same enzyme molecule but may also be located in different enzyme molecules) until the entire synthesis process of the fatty acid is completed. [1] [2] [3] [4] [5]
table of Contents
[ hide ]- 1metabolic function
- Category2
- 3structure
- 4regulation
- 5Disease related
- 6See
- 7References
- 8External links
Metabolic function [ edit ]
Fatty acids are aliphatic acids that play a key role in energy transport and storage, cell structure, and intermediates that provide hormone synthesis. The synthesis of fatty acids requires the completion of acetyl-CoA and malonyl-CoA through a series of Claisen condensation reactions followed by decarboxylation ( biotin as a coenzyme). During the elongation of the fatty chain , the added keto group (thiol) is reduced to a fully saturated fatty chain by the action of successive ketoreductase , dehydratase and enelipid ACP reductases . The aliphatic chain extending enzyme in the active site of the loop transfer between the covalently attached to acyl carrier protein phosphorylation pan acyl mercaptoethylamine (phophopantetheine) prosthetic groups on by a thioesterase is released effect.
Classification [ edit ]
Fatty acid synthases are divided into two major groups:
- Type I is a multifunctional single-chain protein that is ubiquitous in mammals and fungi (although fatty acid synthases in mammals and fungi are structurally distinct).
- Type II, the entire enzyme system consists of multiple single-function enzymes that are present in bacteria .
Structure [ edit ]
Fatty acid synthase in mammals contains two identical multi-function single chains (forming homodimers ). Each N-terminal region of amino acid chains contains three catalytic domains (ketolipid synthase, dehydratase) And the mono- and beta-transferases]]), while the C-terminal region contains four domains (alcohol reductase, ketolipin reductase, thiol carrier protein, and thioesterase), and these two regions are intermediate 600 The amino acid residues are separated by a core region. [6] [7]
The traditional model of fatty acid synthase organization ("head-to-tail" model) is based largely on the bifunctional reagent 1,3-dibromopropanone (DBP) capable of converting a lipid-lipid synthase domain active site onto a fatty acid synthase monomer . The phenomenon that the sulfhydryl group of cysteine (Cys161) on the spot and the phosethoxyethylamine auxiliary group in the carrier protein domain on the other monomer are linked together. [8] [9]
However, mutations in fatty acid synthase dimers have shown that the ketolipin synthase and the mono-/acetyltransferase domain can interact with carrier proteins on any monomer in the dimer; [10] [ 11] A reanalysis of the results of the DBP linkage experiments revealed that the sulfhydryl group of Cys161, the active site of the ketone-lipid synthase, can be linked to the sulfhydryl group of the carrier protein 4'-phosphothioethylamine in either monomer. [12] . Moreover, it has recently been discovered that a heterodimerized fatty acid synthase containing only one intact monomer is capable of palmitate synthesis. [13] The above experimental results are inconsistent with the previous "head-to-tail" model, so another model was proposed: the two monomers on the ketone-lipid synthase and the single-zone/acetotransferase domain are located. Positions close to the center of the fatty acid synthase dimer where they can be contacted with the carrier protein in either monomer. [14]
Regulation [ edit ]
Fatty acid synthase Metabolism and homeostasis by upstream stimulatory factor (Upstream Stimulatory Factor) and sterol regulatory element binding protein (sterol regulatory element binding protein-1c , SREBP-1c) for transcriptional regulation of feeding behavior and to insulin made reaction. [15] [16]
Disease related [ edit ]
The fatty acid synthase gene may be an oncogene . [17] In cancer research, fatty acid synthase levels were found to be upregulated in breast cancer , which can serve as an indicator of inaccurate cancer diagnosis and a potential target for chemotherapy . [18] [19]
See also [ edit ]
- Fatty acid synthesis
- Fatty acid metabolism
- Fatty acid degradation
- Essential fatty acids
References [ edit ]
- ^ Alberts, A.W., Strauss, A.W., Hennessy, S. & Vagelos, P.R. Regulation of synthesis of hepatic fatty acid synthetase: binding of fatty acid synthetase antibodies to polysomes. Proc. Natl. Acad. Sci. USA 72, 3956−3960
- ^ Stoops, J.K. et al. Presence of two polypeptide chains comprising fatty acid synthetase. Proc. Natl. Acad. Sci. USA 72, 1940−1944 (1975)
- ^ Smith, S., Agradi, E., Libertini, L. & Dileepan, K.N. Specific release of the thioesterase component of the fatty acid synthetase multienzyme complex by limited trypsinization. Proc. Natl. Acad. Sci. USA 73, 1184−1188 (1976)
- ^ Wakil, S.J. Fatty acid synthase, a proficient multifunctional enzyme. Biochemistry 28, 4523−4530 (1989)
- ^ Smith, S., Witkowski, A. & Joshi, A.K. Structural and functional organization of the animal fatty acid synthase. Prog. Lipid Res. 42, 289−317
- ^ Chirala, S.S., Jayakumar, A., Gu, Z.W. & Wakil, S.J. Human fatty acid synthase: role of interdomain in the formation of catalytically active synthase dimer. Proc. Natl. Acad. Sci. USA 98, 3104−3108 (2001)
- ^ Smith, S. The animal fatty acid synthase: one gene, one polypeptide, seven enzymes. FASEB J. 8, 1248−1259 (1994)
- ^ Stoops, J.K. & Wakil, S.J. Animal fatty acid synthetase. A novel arrangement of the -ketoacyl synthetase sites comprising domains of the two subunits. J. Biol. Chem. 256, 5128−5133 (1981)
- ^ Stoops, J.K. & Wakil, S.J. Animal fatty acid synthetase. Identification of the residues comprising the novel arrangement of the -ketoacyl synthetase site and their role in its cold inactivation. J. Biol. Chem. 257, 3230−3235
- ^ Joshi, A.K., Rangan, V.S. & Smith, S. Differential affinity labeling of the two subunits of the homodimeric animal fatty acid synthase allows isolation of heterodimers consisting of subunits that have been independently modified. J. Biol. Chem. 273, 4937−4943 (1998)
- ^ Rangan, V.S., Joshi, A.K. & Smith, S. Mapping the functional topology of the animal fatty acid synthase by mutant complementation in vitro. Biochemistry 40, 10792−10799 (2001)
- ^ Witkowski, A. et al. Dibromopropanone cross-linking of the phosphopantetheine and active-site cysteine thiols of the animal fatty acid synthase can occur both inter- and intrasubunit. Reevaluation of the side-by-side, antiparallel subunit model. J. Biol. Chem. 274, 11557−11563 (1999)
- ^ Joshi, A.K., Rangan, V.S., Witkowski, A. & Smith, S. Engineering of an active animal fatty acid synthase dimer with only one competent subunit. Chem. Biol. 10, 169−173 (2003)
- ^ Asturias FJ et al., Structure and molecular organization of mammalian fatty acid synthase. Nature Structural & Molecular Biology 12, 225 - 232 (2005) PMID 15711565
- ^ Paulauskis JD, Sul HS.Hormonal regulation of mouse fatty acid synthase gene transcription in liver.J Biol Chem. 1989 Jan 5;264(1):574-7.
- ^ Latasa MJ, Griffin MJ, Moon YS, Kang C, Sul HS. Occupancy and function of the -150 sterol regulatory element and -65 E-box in nutritional regulation of the fatty acid synthase gene in living animals.Mol Cell Biol. 2003 Aug;23(16):5896-907.
- ^ Baron A, Migita T, Tang D, Loda M. Fatty acid synthase: a metabolic oncogene in prostate cancer?. J Cell Biochem. 2004, 91 (1): 47–53. PMID 14689581. doi:10.1002/jcb.10708.
- ^ Hunt DA. Lane HM. Zygmont ME. Dervan PA. Hennigar RA. MRNA stability and overexpression of fatty acid synthase in human breast cancer cell lines. [Journal Article] Anticancer Research. 27(1A):27-34, 2007 Jan-Feb. UI: 17352212
- ^ Gansler TS. Hardman W 3rd. Hunt DA. Schaffel S. Hennigar RA. Increased expression of fatty acid synthase (OA-519) in ovarian neoplasms predicts shorter survival. [Journal Article] Human Pathology. 28(6):686-92, 1997 Jun. UI: 9191002
External links [ edit ]
- The MeSH (Medical Subject Headings) above Fatty + Acid + Synthase
- Fatty acid synthesis process
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5 categories :
- Human protein
- Transferase
- EC 2.3.1
- metabolism
- fatty acid
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