Summary
Very long chain fatty acids confer functional diversity on cells by variations in their chain length and degree of unsaturation. Microsomal fatty acid elongation represents the major pathway for determining the chain length of saturated, monounsaturated, and polyunsaturated fatty acids in cellular lipids. The overall reaction for fatty acid elongation involves four enzymes and utilizes malonyl CoA, NADPH, and fatty acyl CoA as substrates. While the fundamental pathway and its requirements have been known for many years, recent advances have revealed a family of enzymes involved in the first step of the reaction, i.e., the condensation reaction. Seven fatty acid elongase subtypes (Elovl #1–7) have been identified in the mouse, rat, and human genomes. These enzymes determine the rate of overall fatty acid elongation. Moreover, these enzymes also display differential substrate specificity, tissue distribution, and regulation, making them important regulators of cellular lipid composition as well as specific cellular functions. Herein, methods are described to measure elongase activity, analyze elongation products, and alter cellular elongase expression.
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References
Cook, H.W. 1985. Fatty acid desaturation and chain elongation in eucaryotes. In: Biochemistry of Lipids and Membranes, Eds. Vance, D.E. and Vance, J.E.: Ch. 6, pp. 181–212.
Cinti, D.L., Cook, L., Nagi, M.N. and Suneja, S.K. 1992. The fatty acid chain elongation system of mammalian endoplasmic reticulum. Prog Lipid Res 31: 1–51.
Jakobsson, A., Westerberg, R. and Jacobsson, A. 2006. Fatty acid elongases in mammals: Their regulation and role in metabolism. Prog Lipid Res 45: 237–249.
Leonard, A.E., Pereira, S.L., Sprecher, H. and Huang, Y.S. 2004. Elongation of long-chain fatty acids. Prog Lipid Res 43: 36–54.
Nagi, M.N., Cook, L., Gherquier, D. and Cinti, D.L. 1986. Site of inhibition of rat liver microsomal fatty acid chain elongation system by Dec-2-ynoyl coenzyme A. J Biol Chem 261: 13598–13605.
Westerberg, R., Tvrdik, P., Unden, A-B., Mansson, J-E., Norlen, L., Jakobsson, A., Holleran, W.H., Elias, P.M., Asadi, A., Flodby, P., Toftgard, R., Capecchi, M.R. and Jacobsson, A. 2004. Role for ELOVL3 and fatty acid chain length in development of hair and skin function. J Biol Chem 279: 5621–5629.
Wang, Y., Botolin, D., Christian, B., Busik, C., Xu, J. and Jump, D.B. 2005. Tissue-specific, nutritional and developmental regulation of rat fatty acid elongases. J Lipid Res 46: 706–715.
Wang, Y., Botolin, D., Xu, J., Christian, B., Mitchell, E., Jayaprakasam, B., Nair, M., Peters, J.M., Busik, J., Olson, L.K. and Jump, D.B. 2006. Regulation of hepatic fatty acid elongase and desaturase expression in diabetes and obesity. J Lipid Res 47: 2028–2041.
Moon, Y.A. and Horton, J.D. 2003. Identification of two mammalian reductases involved in the two-carbon fatty acyl elongation cascade. J Biol Chem 278: 7335–7343.
Denic, V. and Weissman, J.S. 2007. A molecular caliper mechanism for determining very long-chain fatty acid length. Cell 130: 663–677.
Beaudoin, F., Gable, K., Sayanova, O., Dunn, T. and Napier, J.A. 2002. A Saccharomyces cerevisiae gene required for heterologous fatty acid elongase activity encodes a microsomal beta-keto-reductase. J Biol Chem 277: 11481–11488.
Moon, Y.A., Shah, N.A., Mohapatra, S., Warrington, J.A. and Horton, J.D.. 2001. Identification of a mammalian long chain fatty acyl elongase regulated by sterol regulatory element-binding proteins. J Biol Chem 276: 45358–45366.
Brolinson, A., Fourcade, S., Jakobsson, A., Pujol, A. and Jacobsson A. 2008. Steroid hormones control circadian Elovl 3 expression in mouse liver. Endocrinology 149: 3158–3166.
Igarashi, M., Ma, K., Chang, L., Bell, J.M. and Rapoport, S.I. 2008. Rat heart cannot synthesize docosahexaenoic acid from circulating a-linolenic acid because it lacks elongase-2. J Lipid Res 49: 1735–1745.
Wang, Y., Botolin, D., Christian, B. and Jump, D.B. 2008. Elevated hepatic expression of fatty acid elongase-5 activity affects multiple pathways controlling hepatic lipid and carbohydrate composition. J Lipid Res 49: 1538–1552.
Pawar, A., and Jump, D.B. 2003. Unsaturated fatty acid regulation of peroxisome proliferator activated receptor-a activity in primary rat hepatocytes. J Biol Chem 278: 35931–35939.
Matsuzaka, T., Shimano, H., Yahagi, N., Kato, T., Atsumi, A., Yamamoto, T., Inoue, N., Ishikawa, M., Okada, S., Ishigaki, N., Iwasaki, H., Iwasaki, Y., Karasawa, T., Kumadaki, S., Matsui, T., Sekiya, M., Ohashi, K., Hasty, A.H., Nakagawa, Y., Takahashi, A., Suzuki, H., Yatoh, S., Sone, H., Toyoshima, H., Osuga, J. and Yamada, N. 2007. Crucial role of a long-chain fatty acid elongase, Elovl6, in obesity-induced insulin resistance. Nat Med 13: 1193–1202.
Kobayashi, T., Zadravec, D. and Jacobsson, A. 2007. ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3-L1 and F442A cells. FEBS Lett 581: 3157–3163.
Hamilton, J.A., Era, S., Bhamidipati, S.P. and Reed, R.G. 1991. Locations of the three primary binding sites for long-chain fatty acids on bovine serum albumin. Proc Natl Acad Sci U S A 88: 2051–2054.
Acknowledgments
This research was supported by the National Institutes of Health, DK43220. I would like to thank Dr. Moises Torres-Gonzalez and Sasmita Tripathy for critical reading of this manuscript.
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Jump, D.B. (2009). Mammalian Fatty Acid Elongases. In: Armstrong, D. (eds) Lipidomics. Methods in Molecular Biology, vol 579. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-322-0_19
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DOI: https://doi.org/10.1007/978-1-60761-322-0_19
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