Fatty acid synthase

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Fatty acids are aliphatic acids fundamental to energy production and storage, cellular structure and as intermediates in the biosynthesis of hormones and other biologically important molecules. They are synthesised by a series of decarboxylative Claisen condensation reactions from Acetyl-CoA and Malonyl-CoA. Following each round of elongation the beta keto group is reduced to the fully saturated carbon chain by the action of a ketoreductase, enol reductase and dehydratase.

The growing fatty acid chain is carried as an acyl carrier protein linked substrate, and is released by the action of a thioesterase.

There are two principal classes of fatty acid synthases.

Type I systems utilise a single large, multifunctional polypeptide and are common to both mammals and fungi (although the structural arrangement of fungal and mamallian synthases differ).
Type II, or bacterial systems, use discrete, monofunctional enzymes which are used iteratively to elongate and reduce the fatty acid chain.

Metabolism and homeostasis of fatty acid is regulated by liver X receptor(LXRs). LXRs regulate fatty acid synthesis by modulating the expression of sterol regulatory elementbinding protein-1c (SREBP-1c).^[1]^[2]

It has been investigated as a possible oncogene.^[3]

FAS is up-regultaed in breast cancers and as well as being an indicator of poor prognosis may also be worthwhile as a chemotheraputic target. (ref#4 &5)

[edit] See also

Fatty acid synthesis

[edit] References

^ Yoshikawa T, Shimano H, Amemiya-Kudo M, Yahagi N, Hasty AH, Matsuzaka T, Okazaki H, Tamura Y, Iizuka Y, Ohashi K, Osuga J, Harada K, Gotoda T, Kimura S, Ishibashi S, Yamada N. Identification of liver X receptor-retinoid X receptor as an activator of the sterol regulatory element-binding protein 1c gene promoter. Mol Cell Biol. 2001 May;21(9):2991-3000. PMID 11287605
^ Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, Shan B, Brown MS, Goldstein JL, Mangelsdorf DJ. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 2000 Nov 15;14(22):2819-30. PMID 11090130
^ Baron A, Migita T, Tang D, Loda M (2004). "Fatty acid synthase: a metabolic oncogene in prostate cancer?". J Cell Biochem 91 (1): 47-53. PMID 14689581.

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

[edit] External links

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