Biochemical and physiological function of stearoyl-CoA desaturase

American Journal of Physiology - Endocrinology and Metabolism - Tập 297 Số 1 - Trang E28-E37 - 2009
Chad M. Paton1, James M. Ntambi
1Dept. of Biochemistry, Univ. of Wisconsin, 433 Babcock Dr., Madison, WI 53706, USA.

Tóm tắt

A key and highly regulated enzyme that is required for the biosynthesis of monounsaturated fatty acids is stearoyl-CoA desaturase (SCD), which catalyzes the D9- cis desaturation of a range of fatty acyl-CoA substrates. The preferred substrates are palmitoyl- and stearoyl-CoA, which are converted into palmitoleoyl- and oleoyl-CoA respectively. Oleate is the most abundant monounsaturated fatty acid in dietary fat and is therefore readily available. Studies of mice that have a naturally occurring mutation in the SCD-1 gene isoform as well as a mouse model with a targeted disruption of the SCD gene (SCD-1−/−) have revealed the role of de novo synthesized oleate and thus the physiological importance of SCD-1 expression. SCD-1 deficiency results in reduced body adiposity, increased insulin sensitivity, and resistance to diet-induced obesity. The expression of several genes of lipid oxidation are upregulated, whereas lipid synthesis genes are downregulated. SCD-1 was also found to be a component of the novel metabolic response to the hormone leptin. Therefore, SCD-1 appears to be an important metabolic control point, and inhibition of its expression could be of benefit for the treatment of obesity, diabetes, and other metabolic diseases. In this article, we summarize the recent and timely advances concerning the important role of SCD in the biochemistry and physiology of lipid metabolism.

Từ khóa


Tài liệu tham khảo

10.1194/jlr.M200189-JLR200

10.1074/jbc.271.5.2594

10.1021/ja012252l

10.1016/j.ceb.2007.02.004

10.2337/diabetes.54.5.1314

10.1038/oby.2008.39

10.1016/S0162-0134(99)00199-3

10.1007/s00125-005-0105-3

10.1152/ajpendo.90248.2008

10.1016/j.cell.2008.07.048

10.1074/jbc.M705656200

10.1128/MCB.00077-06

10.1007/s00125-006-0383-4

10.1073/pnas.0401627101

10.1152/ajpendo.00471.2007

Enoch HG, Catala A, Strittmatter P.Mechanism of rat liver microsomal stearyl-CoA desaturase. Studies of the substrate specificity, enzyme-substrate interactions, and the function of lipid.J Biol Chem251: 5095–5103, 1976.

10.1194/jlr.M600203-JLR200

10.1046/j.1523-1747.2003.12134.x

Hardy S, Langelier Y, Prentki M.Oleate activates phosphatidylinositol 3-kinase and promotes proliferation and reduces apoptosis of MDA-MB-231 breast cancer cells, whereas palmitate has opposite effects.Cancer Res60: 6353–6358, 2000.

10.1074/jbc.M709471200

10.1196/annals.1320.002

Kaestner KH, Ntambi JM, Kelly TJ Jr, Lane MD.Differentiation-induced gene expression in 3T3-L1 preadipocytes. A second differentially expressed gene encoding stearoyl-CoA desaturase.J Biol Chem264: 14755–14761, 1989.

Kim YC, Gomez FE, Fox BG, Ntambi JM.Differential regulation of the stearoyl-CoA desaturase genes by thiazolidinediones in 3T3-L1 adipocytes.J Lipid Res41: 1310–1316, 2000.

10.1016/S1097-2765(00)80210-5

10.1194/jlr.M600172-JLR200

10.1074/jbc.M508733200

10.1161/ATVBAHA.107.160150

10.1093/oxfordjournals.jbchem.a123301

10.1172/JCI8538

10.1073/pnas.0503132102

10.1074/jbc.M402781200

10.1016/j.cmet.2007.10.014

10.1194/jlr.M200271-JLR200

10.1074/jbc.M304724200

10.1074/jbc.M106442200

10.1074/jbc.M005488200

10.1093/jn/131.9.2260

10.1073/pnas.97.16.8883

Nagai J, Bloch K.Synthesis of oleic acid by Euglena gracilis.J Biol Chem240: C3702–C3703, 1965.

Ntambi JM, Buhrow SA, Kaestner KH, Christy RJ, Sibley E, Kelly TJ Jr, Lane MD.Differentiation-induced gene expression in 3T3-L1 preadipocytes. Characterization of a differentially expressed gene encoding stearoyl-CoA desaturase.J Biol Chem263: 17291–17300, 1988.

Ntambi JM.Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol.J Lipid Res40: 1549–1558, 1999.

10.1073/pnas.132384699

10.2337/diabetes.51.2.271

10.1016/j.numecd.2007.02.017

10.1093/jn/124.9.1555

10.1097/gme.0b013e31817b8159

Payne AP.The harderian gland: a tercentennial review.J Anat185: 1–49, 1994.

10.1152/ajpendo.00022.2008

10.1002/hep.22334

10.1073/pnas.1934571100

10.2217/17460875.3.2.163

10.1074/jbc.M103587200

Stukey JE, McDonough VM, Martin CE.The OLE1 gene of Saccharomyces cerevisiae encodes the delta 9 fatty acid desaturase and can be functionally replaced by the rat stearoyl-CoA desaturase gene.J Biol Chem265: 20144–20149, 1990.

10.1016/S0002-9440(10)65078-X

10.1007/s00125-005-1897-x

10.1038/oby.2007.206

10.1016/j.bbrc.2007.12.190

10.1110/ps.04951405

Zhang S, Skalsky Y, Garfinkel DJ.MGA2 or SPT23 Is required for transcription of the delta9 fatty acid desaturase gene, OLE1, and nuclear membrane integrity in Saccharomyces cerevisiae.Genetics151: 473–483, 1999.

Thông tin
Thông tin xuất bản

American Journal of Physiology - Endocrinology and Metabolism

Tập 297 Số 1

E28-E37

Thông tin tác giả