Stearoyl CoA desaturase

Considerable variation among cows (Kinsella, 1972 Kelsey et al., 2003) and breeds (DePeters et al., 1995) in the extent of stearic acid desaturation and in mRNA expression (Taniguchi et al., 2004) has been observed. SCD mRNA expression is down-regulated by trans-10, cis-12 Ci8 2 (Choi et al., 2000), which is formed in the rumen in small amounts when milk fat-depressing diets are fed (Bauman and Griinari, 2003). 

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This impressive reaction is catalyzed by stearoyl-CoA desaturase, a 53-kD enzyme containing a nonheme iron center. NADH and oxygen (Og) are required, as are two other proteins cytochrome 65 reductase (a 43-kD flavo-protein) and cytochrome 65 (16.7 kD). All three proteins are associated with the endoplasmic reticulum membrane. Cytochrome reductase transfers a pair of electrons from NADH through FAD to cytochrome (Figure 25.14). Oxidation of reduced cytochrome be, is coupled to reduction of nonheme Fe to Fe in the desaturase. The Fe accepts a pair of electrons (one at a time in a cycle) from cytochrome b and creates a cis double bond at the 9,10-posi-tion of the stearoyl-CoA substrate. Og is the terminal electron acceptor in this fatty acyl desaturation cycle. Note that two water molecules are made, which means that four electrons are transferred overall. Two of these come through the reaction sequence from NADH, and two come from the fatty acyl substrate that is being dehydrogenated. 

FIGURE 25.14 The conversion of stearoyl-CoA to oleoyl-CoA in eukaryotes is catalyzed by stearoyl-CoA desaturase in a reaction sequence that also involves cytochrome -65 and cytochrome -65 reductase. Two electrons are passed from NADH through the chain of reactions as shown, and two electrons are also derived from the fatty acyl substrate. 

Carefully study the reaction mechanism for the stearoyl-CoA desaturase in Figure 25.14, and account for all of the electrons flowing through the reactions shown. Also account for all of the hydrogen and oxygen atoms involved in this reaction, and convince yourself that the stoichiometry is correct as shown. 

This enzyme [EC 1.14.99.5], also known as stearoyl-CoA desaturase, fatty acid desaturase, and A -desaturase, will catalyze the reaction of stearoyl-CoA with a hydrogen donor and dioxygen to produce oleoyl-CoA, water, and... 

Morgan-Lappe SE, Tucker LA, Huang X et al (2007) Identification of Ras-related nuclear protein, targeting protein for xenopus kinesin-like protein 2, and stearoyl-CoA desaturase 1 as promising cancer targets from an RNAi-based screen. Cancer Res 67 4390-4398... 

Sessler, A. M., Kaur, N., Palta, J. P., and Ntambi, J. M. (1996). Regulation of stearoyl-CoA desaturase 1 mRNA stability by polyunsaturated fatty acids in 3T3-L1 adipocytes. ]. Biol. Chem. 271, 29854-29858. 

Desaturation requires the cooperative action of two enzymes Cytochrome b5 reductase and stearoyl-CoA desaturase, in addition to an electron carrier protein, cyto-... 

Kaestner K. H., Ntambi J. M., Kelly T. J. and Lane, M. D. (1989) Differentiation-induced gene expression in 3T3-L1 preadipocytes - a second differentially expressed gene encoding stearoyl-CoA desaturase. J. Biol. Chem. 264, 14755-14761. 

Shanklin J., Whittle E. and Fox B. G. (1994) Eight histidine residues are catalytically essential in a membrane associated iron enzyme, stearoyl-CoA desaturase and are conserved in alkane hydroxylase and xylene monooxygenase. Biochem. 33, 12787-12794. 

Strittmatter P., Thiede M. A., Hackett C. S. and Ozols J. (1988) Bacterial synthesis of active rat stearoyl-CoA desaturase lacking the 26-residue amino-terminal amino acid sequence. J. Biol. Chem. 263, 2532-2535. 

Stukey J. E., McDonough V. M. and Martin C. E., (1990) The OLE1 gene of Saccharomyces cerevisiae encodes the A9 fatty acid desaturase and can be functionally replaced by the rat stearoyl-CoA desaturase gene. J. Biol. Chem. 265, 20144-20149. 

Lee K. N., Pariza M. W. and Ntambi J. M. (1996) Differential expression of hepatic stearoyl-CoA desaturase gene 1 in male and female mice. Bioch. Biophys. Acta 1304, 85-88. 

Zheng Y., Prouty S. M., Harmon A., Sundberg J. P., Stenn K. S. and Parimoo S. (2001) Scd.3 - a novel gene of the stearoyl-CoA desaturase family with restricted expression in skin. Genomics 71, 182-191. 

Bernard, L., Leroux, C., Hayes, H., Gautier, M., Chilliard, Y., Martin, P. 2001. Characterization of the caprine stearoyl-CoA desaturase gene and its mRNA showing an unusually long 3 -UTAR sequence arising from a single exon. Gene. 281, 53-61. 

Chang, J.H.P., Lunt, D.K., Smith, S.B. 1992. Fatty acid composition and fatty acid elongase and stearoyl-CoA desaturase activities in tissues of steers fed high oleate sunflower seed. J. Nutr. 122, 2074-2080. 

Choi, Y., Kim, Y-C., Han, Y-B., Park, Y., Pariza, M.W., Ntambi, J.M. 2000. The trans-10, dr-12 isomer of conjugated linoleic acid downregulates stearoyl-CoA desaturase 1 gene expression in 3T3-L1 adipocytes. J. Nutr. 130, 1920-1924. 

Ntambi, J.M., Miyazaki, M. 2004. Regulation of stearoyl-CoA desaturases and role in metabolism. Prog. Lipid Res. 43, 91-104. 

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