Fatty acid synthesis plays a vital role in homeostasis within the human body. The process of fatty acid synthesis regulates energy metabolism and provides fuel in times of starvation1. This process also synthesizes biomolecules that are important to life during embryonic development and lactation in mammary glands2. An overproduction of synthesized fatty acids is implicated in disease states such as obesity, liver disease, and cancer3.
The fatty acid synthase (FAS) complex performs a vital role in fatty acid synthesis. While there are two FAS complexes known, FAS I is the complex present in eukaryotes and higher prokaryotes4. Despite the difference in complexes utilized, the steps of fatty acid synthesis are, for the most part, conserved in all life4. FAS I is a homo dimer of ~272-kd subunits and contains three N-terminal active domains, each comprising a number of catalytic sites2,5. There are seven known catalytic sites in the FAS I complex, linked together by a polypeptide chain2,5. These include β-ketoacyl synthase (KS), malonyl/acetyltransferase (MAT), dehydrogenase (DH), enoyl reductase (ER), β -ketoacyl reductase (KR), acyl carrier protein (ACP) and thioesterase (TE)6. These sites facilitate the reactions necessary for fatty acid synthesis to occur (see fig 1).
Figure 1. Diagram of the FAS I complex showing each of the seven catalytic sites6
Overexpression of FAS I is common in some types of cancers. Therefore, inhibition of FAS I is of significant note because anti-cancer therapies targeted to inhibit FAS I have the possibility of being an effective cancer treatment. This review will discuss the regulation of fatty acid synthesis, examine the biochemical reactions involved in fatty acid synthesi...
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...Iwaya K. Prognostic impact of fatty acid synthase expression in upper urinary tract urothelial carcinoma. Journal of Clinical Oncology, 2014; 44 (4): 1093
Swierczynski J. Hebanowska A. Sledzinski T. Role of abnormal lipid metabolism in development, progression, diagnosis and therapy of pancreatic cancer. World Journal of Gasteroenterology, 2014; 20(9): 2279–2303.
Ito T. Sato K. Maekawa H. Sakurada M. Orita H. Shimada K. Daida H. Wada R. Abe M. Hino O. Kajiyama Y. Elevated levels of serum fatty acid synthase in patients with gastric carcinoma. Oncology Letters, 2014; 7(3):616-620
Uddin S. Siraj AK. Al-Rasheed M. Ahmed M. Bu R. Myers JN. Al-Nuaim A. Al-Sobhi S. Al-Dayel F. Bavi P. Hussain AR. Al-Kuraya KS. Fatty acid synthase and AKT pathway signaling in a subset of papillary thyroid cancers. Journal of Clinical Endocrinology Metabolism, 2008; 93(10):4088-97
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