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Essay / Fatty acid synthesis and cancer - 1310
IntroductionThe synthesis of fatty acids plays an essential role in the homeostasis of the human body. The process of fatty acid synthesis regulates energy metabolism and provides fuel in times of starvation1. This process also synthesizes biomolecules important for life during embryonic development and lactation in the mammary glands2. An overproduction of synthesized fatty acids is implicated in pathological conditions such as obesity, liver disease and cancer3. The fatty acid synthase (FAS) complex plays an essential role in the synthesis of fatty acids. Although there are two known FAS complexes, FAS I is the complex found in eukaryotes and higher prokaryotes4. Despite the difference in the complexes used, the steps of fatty acid synthesis are, for the most part, conserved throughout life4. FAS I is a homodimer of approximately 272 kd subunits and contains three N-terminal active domains, each comprising a number of catalytic sites. There are seven known catalytic sites in the FAS I complex, linked together by a 2,5 polypeptide chain. 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 the synthesis of fatty acids (see fig 1). Figure 1. Diagram of the FAS I complex showing each of the seven catalytic sites6Overexpression of FAS I is common in certain types of cancer. Therefore, inhibition of FAS I is of particular importance, as anticancer therapies aimed at inhibiting FAS I have the potential to be an effective treatment for cancer. This review will discuss the regulation of fatty acid synthesis, examine the biochemical reactions involved in fatty acid synthesis...... middle of article ......Iwaya K. Prognostic impact of expression of fatty acid synthase in upper urinary tract urothelial carcinoma. Journal of Clinical Oncology, 2014; 44 (4): 1093Swierczynski J. Hebanowska A. Sledzinski T. Role of abnormal lipid metabolism in the development, progression, diagnosis and treatment of pancreatic cancer. World Journal of Gastroenterology, 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. High levels of fatty acid synthase serum 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 synthesis and AKT pathway signaling in a subset of papillary thyroid cancers. Journal of Clinical Endocrinology Metabolism, 2008; 93(10):4088-97