Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
evolution
isozymes SCD1 and SCD3 share 89% primary sequence identity, but they yield remarkably different total fatty acid profiles in the recombinant yeast host cells, likely reflecting differences in their preferences for reaction with 16:0 and 18:0 substrates
malfunction
-
alterations in expression reported in several prevalent metabolic diseases, such as diabetes, obesity and atherosclerosis
malfunction
-
enzyme inhibition by genetic and chemical tools is detrimental for parasite development. The partial ablation of the enzyme inhibits drastically the parasite growth
malfunction
-
stearoyl-CoA desaturase 1 deficiency is coupled with an extreme cold sensitivity and significantly increased skin inflammation
malfunction
-
the ablation of enzyme activity has an immediate and profound impact on the fatty acid content of cell lipids. Enzyme inhibition alters the epidermal growth factor-dependent signaling mechanism, decreases the mobility of fluid domains in plasma membranes, and reduces EGF-induced proliferation in lung cancer cells
malfunction
chemical SCD1 inhibition in the presence of stearic acid results in a significant induction of apoptosis in cumulus cells of matured cumulus-oocyte complexes. SCD1 inhibition does not affect the levels of palmitic acid and its desaturated form, palmitoleic acid
malfunction
dysregulation of stearoyl-CoA desaturase 1 likely contributes to obesity associated metabolic disturbances. Effect of genetic ablation of SCD1 in 3T3-L1 adipocytes on membrane microdomain lipid composition at the species-specific level, overview. 90% reduction in scd1 mRNA expression, caused by siRNA expression, leads to altered cellular lipid composition, SCD1 knockout modifies the acyl chain composition of lipids, as well as the lipid composition per se of membrane microdomains in 3T3-L1 adipocytes.The effects of SCD1 knockout are not limited to alterations in 16:0 and 18:0 fatty acids. Cholesterol content is unchanged although decreases in other lipids result in cholesterol accounting for a higher proportion of lipid in the membranes. This is associated with decreased membrane lateral diffusion. An increased ratio of 24:0 to 24:1 in ceramide, mono- and dihexosylceramide, and sphingomyelin likely also contributes to this decrease in lateral diffusion. Lipidomic profiling is targeted to specific membrane microdomains, overview. A decrease in phospholipids containing arachidonic acid is observed. Given the high degree of structural flexibility of this acyl chain this will influence membrane lateral diffusion, and is likely responsible for the transcriptional activation of Lands' cycle enzymes lpcat3 and mboat7
malfunction
inhibition of SCD1 activity represents a potential novel approach for the treatment of metabolic diseases such as obesity, type 2 diabetes and dyslipidemia, as well as skin diseases, acne and cancer
malfunction
inhibition of SCD1 activity represents a potential novel approach for the treatment of metabolic diseases such as obesity, type 2 diabetes and dyslipidemia, as well as skin diseases, acne and cancer
malfunction
loss of SCD-1 activity induces complex changes in the fatty acid composition of membrane lipids which are not restricted to the MUFA/SFA ratio. SCD-1 deficiency induces insulin signaling in peripheral tissues, namely phosphorylation of insulin receptor and insulin receptor substrates (IRS)1 and 2. Association of IRS isoforms with the regulatory subunit of phosphatidylinositol-3-kinase (PI3K) promotes the synthesis of phosphatidylinositol-3,4,5-trisphoshates (PIP3) as membrane anchor sites for the serine/threonine kinase Akt. SCD-1 inhibition suppressed starvation-induced autophagy in mouse embryonic fibroblasts and palmitate-induced autophagy in rat pancreatic beta-cells apparently by disturbing autophagosome-lysosome fusion
malfunction
loss of SCD-1 activity induces complex changes in the fatty acid scomposition of membrane lipids which are not restricted to the MUFA/SFA ratio. SCD-1 deficiency induces insulin signaling in peripheral tissues, namely phosphorylation of insulin receptor and insulin receptor substrates (IRS)1 and 2. Association of IRS isoforms with the regulatory subunit of phosphatidylinositol-3-kinase (PI3K) promotes the synthesis of phosphatidylinositol-3,4,5-trisphoshates (PIP3) as membrane anchor sites for the serine/threonine kinase Akt
malfunction
reduced SCD1 activity in the liver causes endoplasmic reticulum stress that is only normalized by exogenous or endogenous oleate but not palmitoleate. SCD1 deficiency-mediated glucose uptake in skeletal muscle and brown adipose tissue feeds toward glycogen synthesis. Localized and systemic SCD1 deficiency increases glucose uptake in white adipose tissue through apparently different mechanisms involving GLUT1 and GLUT4, respectively
malfunction
reduced SCD1 activity in the liver causes endoplasmic reticulum stress that is only normalized by exogenous or endogenous oleate but not palmitoleate. SCD1 deficiency-mediated glucose uptake in skeletal muscle and brown adipose tissue feeds toward glycogen synthesis. Localized and systemic SCD1 deficiency increases glucose uptake in white adipose tissue through apparently different mechanisms involving GLUT1 and GLUT4, respectively. Liver-specific SCD1 KO mice exhibit different phenotypes compared to skin-specific SCD1 KO mice, suggesting that SCD1 products, monounsaturated fatty acids, carry out different functions in different tissues. Global SCD1 KO mice are protected against high carbohydrate diet and high fat diet-induced adiposity and hepatic steatosis. Liver-specific SCD1 knockout mice fed high-fat diet show a significant reduction of white adipose tissue weights compared with control mice. Hepatic SCD1 deficiency causes a significant reduction in hepatic lipogenic gene expression and reduced de novo lipogenesis associated with reduced hepatic triglyceride secretion. Skin-specific knockout mice show protection against high-fat diet-induced adiposity along with increased energy expenditure expected to be sufficient to counter increased calorie intake associated with feeding high-fat diet. In addition, similar to SCD1 global KO mice, skin-specific KO mice are hyperphagic and maintain lean phenotype accompanied by protection against extended high-fat diet feeding-induced insulin resistance. Skin-specific KO mice exhibit increased cold sensitivity and died within 3 h of cold exposure due to hypoglycemia. SCD1 isozyme-specific knockout phenotypes with respect to the other isozymes, detailed overview
malfunction
reduction of SCD1 activity and mRNA expression impaired the formation of cell membrane lipids with the decrease of fatty acid biosynthesis and desaturation, leading to cease cancer cell proliferation and induction of cell apoptosis. Inhibition of stearoyl-CoA desaturase 1 (SCD1) effectively suppresses tumor cell proliferation and induce apoptosis in numerous neoplastic lesions, SCD1-mediated anti-tumor effect. Endo-lipid messenger ceramides play a critical role in tumor fate modulated by SCD1 inhibition. Inhibition of SCD1 activity promotes apoptosis attributed to mitochondria dysfunctions, upregulation of reaction oxygen species (ROS), alteration of mitochondrial transmembrane potential, and translocation of mitochondrial protein cytochrome C in colorectal cancer cells. These effects are mediated by intracellular ceramide signals through induction of ceramide biosynthesis, rather than exclusive saturated fatty acid accumulation. Inhibitor A939 dramatically increases intracellular long-chain saturated ceramide levels including C18:0 ceramide, C20:0 ceramide, C22:0 ceramide, and C24:0 ceramide, while it slightly increases middle-chain saturated ceramide C16:0 and does not affect monounsaturated C24:1 ceramide
malfunction
siRNA against SCD1 exacerbates the apoptosis
malfunction
stearoyl-CoA desaturase 1 (SCD-1) inhibition blocks hepatitis C virus replication and formation of hepatitis C virus-induced specialized membranes. Inhibition of stearoyl-CoA desaturase 1 halts the biosynthesis of unsaturated fatty acids, such as oleic acid, and negatively modulates HCV replication. Unsaturated fatty acids play key roles in membrane curvature and fluidity, SCD-1 inhibition disrupts the integrity of membranous HCV replication complexes and renders HCV RNA susceptible to nuclease-mediated degradation
malfunction
targeting SCD1 synergizes the effect of sorafenib both in vitro and in vivo. The endoplasmic reticulum stress-induced unfolded protein response is upregulated in SCD1-knockdown cells. Suppression of SCD1 forces liver cancer stem cells to differentiate via the induction of endoplasmic reticulum stress, which results in their enhanced sensitivity to sorafenib both in vitro and in vivo. SCD1 knockdown reduces stem/progenitor characteristics of hepatocellular carcinoma cells
malfunction
-
enzyme inhibition by genetic and chemical tools is detrimental for parasite development. The partial ablation of the enzyme inhibits drastically the parasite growth
-
metabolism
-
SCD is critical in the biosynthesis of triglycerides, cholesterol esters, wax esters, and 1-alkyl-2,3-diacylglycerol
metabolism
sex-pheromone biosynthesis
metabolism
-
stearoyl-CoA desaturase 1 is the rate-limiting enzyme in the biosynthesis of monounsaturated fatty acids and a risk factor of diabetes
metabolism
-
the enzyme is necessary for proper liver, adipose tissue, and skeletal muscle lipid metabolism
metabolism
cross-talk of SCD1-mediated lipid pathway and endo-ceramide biosynthesis pathway, indicating roles of ceramide signals in SCD1-mediated anti-tumor property
metabolism
isozyme SCD1 has a role in adipogenesis and lipid biosynthesis
metabolism
isozyme SCD1 has a role in adipogenesis and lipid biosynthesis
metabolism
stearoyl-CoA desaturase-1 (SCD1) plays an important role in lipid metabolism
metabolism
stearoyl-CoA desaturase-1 (SCD1) plays an important role in lipid metabolism
metabolism
survival and stress-activated signaling pathways are regulated by SCD-1, molecular link between SCD-1 activity and cell signaling, overview
metabolism
survival and stress-activated signaling pathways are regulated by SCD-1, molecular link between SCD-1 activity and cell signaling, overview
metabolism
the enzyme is involved in the metabolism of free fatty acids
physiological function
-
absence of stearoyl-CoA desaturase-1 leads to chronic inflammation of the skin and increased susceptibility to atherosclerosis, while also increasing plasma inflammatory markers, but does not promote dextran sulfate sodium-induced acute colitis
physiological function
-
mice lacking Scd1 are protected from obesity and insulin resistance and are characterized by decreased fatty acid synthesis and increased fatty acid oxidation
physiological function
-
mice with a skin-specific deletion of SCD1 (SKO) have significantly increased energy expenditure, are protected from high fat diet-induced obesity, and display marked sebaceous gland hypoplasia and depletion of sebaceous lipids. SKO mice display severe cold intolerance because of rapid depletion of fuel substrates, including hepatic glycogen, to maintain core body temperature. Unlike mice globally deficient in SCD1, SKO mice have an intact hepatic lipogenic response to acute high carbohydrate feeding
physiological function
-
SCD-1 knockout mice show reduced body adiposity, increased insulin sensitivity, leanness, increased metabolic rate, and resistance to diet-induced obesity
physiological function
-
SCD1 knockout mice on the methionine-choline-deficient diet have decreased steatosis and markedly increased hepatocellular apoptosis, liver injury, and fibrosis compared with the SCD-expressing mice
physiological function
-
Scd1 null mice are more susceptible to dextran sulfate sodium treatment than wild type mice, while oleic acid feeding and in vivo SCD1 rescue with SCD1 adenovirus alleviates the dextran sulfate sodium-induced phenotype
physiological function
-
key regulator of lipid fatty acid composition
physiological function
-
enzyme expression is important in regulating lipid bilayer fluidity, increasing triglyceride formation, and enabling lipogenesis and may protect against saturated fatty acids-induced lipotoxicity
physiological function
-
skin stearoyl-CoA desaturase 1 regulates skin integrity and energy balance
physiological function
-
the enzyme activity is the most critical determinant of the monounsaturated/saturated fatty acid balance in cancer cells
physiological function
-
both SCD genes from an Antarctic marine copepod encode a functional desaturase that is capable of increasing the amounts of palmitoleic acid and oleic acid in a prokaryotic expression system
physiological function
cumulus cells can desaturate the potentially toxic stearic acid into oleic acid via stearoyl-CoA desaturase (SCD) activity, cumulus cells protect the oocyte against toxicity by saturated fatty acids. Stearoyl-CoA desaturase 1 activity is related with increased lipid storage in cumulus cells. The level of SCD protein expression in cumulus cells does not change when cumulus-oocyte complexes (COCs) are exposed to saturated stearic acid during maturation
physiological function
oleic acid stimulation of motility of human extravillous trophoblast cells is mediated by stearoyl-CoA desaturase-1 activity. SCD1 is a key enzyme involved in oleic acid-induced migration of HTR8/SVneo cells. Regulatory effects of oleic acid and SCD1 on oxidative stress in HTR8/SVneo cells, effects of oleic acid and elaidic acid on proliferation and migration of HTR8/SVneo cell lines, overview
physiological function
stearoyl-CoA desaturase (SCD) introduces the first double bond into saturated fatty acyl-CoAs. Since the monounsaturated products of SCD are key precursors of membrane phospholipids, cholesterol esters, and triglycerides, SCD is pivotal in fatty acid metabolism
physiological function
stearoyl-CoA desaturase (SCD), the central enzyme in the biosynthesis of monounsaturated fatty acids, introduces a cis-DELTA9 double bond into saturated fatty acids. SCD-1 induces adaptive stress signaling that maintains cellular persistence and fosters survival and cellular functionality under distinct pathological conditions. Function, regulation, structure and mechanism of SCD-1, molecular mechanisms and potential lipid factors that link SCD-1 activity with initial signal transduction, overview. SCD-1 is the major isoenzyme responsible for monounsaturated fatty acid biosynthesis in most rodent tissues. SCD-1 is critical for cell proliferation, especially in hyperproliferative cells, such as cancer cells. Another mechanism bywhich SCD-1 modulates overall lipid metabolism depends on the negative regulation of the lipogenic transcription factor SREBP-1c, thereby reducing lipid biosynthesis and enhancing beta-oxidation of fatty acids. SCD-1 has a dual function in the regulation of autophagy by either promoting or inhibiting autophagy depending on the experimental settings and stress conditions
physiological function
stearoyl-CoA desaturase (SCD), the central enzyme in the biosynthesis of monounsaturated fatty acids, introduces a cis-DELTA9 double bond into saturated fatty acids. SCD-1 induces adaptive stress signaling that maintains cellular persistence and fosters survival and cellular functionality under distinct pathological conditions. The enzyme is a key player that links lipid metabolism with adaptive stress signaling and multiple diseases such as metabolic syndrome, skin disorders, cardiovascular disease and cancer. Function, regulation, structure and mechanism of SCD-1, molecular mechanisms and potential lipid factors that link SCD-1 activity with initial signal transduction, overview. SCD-1 is the major isoenzyme responsible for monounsaturated fatty acid biosynthesis in most human tissues. SCD-1 is critical for cell proliferation, especially in hyperproliferative cells, such as cancer cells. Another mechanism bywhich SCD-1 modulates overall lipid metabolism depends on the negative regulation of the lipogenic transcription factor SREBP-1c, thereby reducing lipid biosynthesis and enhancing beta-oxidation of fatty acids. SCD-1 has a dual function in the regulation of autophagy by either promoting or inhibiting autophagy depending on the experimental settings and stress conditions
physiological function
stearoyl-CoA desaturase 1 is a lipogenic enzyme important for the regulation of membrane lipid homeostasis. The enzyme catalyses the insertion of a cis double bond in 12-19 carbon saturated fatty acids, thereby converting them to monounsaturated fatty acids. Through this activity, SCD1 helps to regulate the ratio of saturated to monounsaturated acyl chains in membrane lipids influencingmembrane fluidity and functionality, both essential for maintaining cellular integrity. Adaptive homeostatic mechanisms to ensure partial maintenance of the biophysical properties of membranes likely occur at a post-transcriptional level
physiological function
stearoyl-CoA desaturase is a key enzyme in the biosynthesis of oleic acid, role of SCD-1 in the fatty acid biosynthesis pathway, schematic overview. SCD-1 catalyzes the fatty acids desaturation at carbon-9 forming a cis-double bond. The SCD-1 produced products, palmitoleoyl-CoA (C16:1) and oleoyl-CoA (C18:1), are directly incorporated in triglycerides, cholesterol esters, and phospholipids. These lipids are crucial to the formation of cytosolic lipid droplets, luminal lipid domains, and lipid-rich membranes, which are platforms for hepatitis C virus replication and assembly. Analysis of the influence of SCD-1 on the nuclease and detergent resistant properties of viral RNA at replication complexes
physiological function
stearoyl-CoA desaturase regulates liver tumorinitiating cells and resistance to sorafenib, a drug in treatment of hepatocellular carcinoma, via modulation of endoplasmic reticulum stress-induced differentiation, functional roles of SCD1 in regulating liver tumor-initiating cells and sorafenib resistance, SCD1 maintains liver tumor-initiating cells by suppressing differentiation intervening in the differentiation process, overview
physiological function
stearoyl-CoA desaturase-1 (SCD1) catalyzes saturated fatty acids to DELTA-9 monounsaturated fatty acids, e.g. converting palmitic acid (C16:0) to palmitoleic acid (C16:1) or converting stearic acid (C18:0) to oleic acid (C18:1). SCD1 is necessary to stimulate lipid biosynthesis to supply new phospholipids for cell membrane biogenesis in cell cycle process of mitosis
physiological function
stearoyl-CoA desaturase-1, SCD1, is an enzyme that desaturates satruated fatty acids (SFA), converting them to monounsaturated fatty acids (MUFAs), leading to the formation of neutral lipid droplets. SCD1 activity protects cells against lipotoxicity-mediated apoptosis in proximal tubular cells. In culture, retrovirus-mediated overexpression of SCD1 or MUFA treatment significantly ameliorates saturated fatty acid-induced apoptosis in proximal tubular epithelial cells by enhancing intracellular lipid droplet formation. Both overexpression of SCD1 and monounsaturated fatty acid treatment reduces SFA-induced apoptosis via reducing endoplasmic reticulum stress in cultured proximal tubular epithelial cells
physiological function
stearoyl-coenzyme A desaturase 1 (SCD1) is a central regulator of fuel metabolism. SCD1 catalyzes the synthesis of monounsaturated fatty acids (MUFAs), mainly oleate and palmitoleate, which are important in controlling weight gain in response to feeding high carbohydrate diets, role of SCD1 isoform in the regulation of lipid and glucose metabolism in metabolic tissues. SCD1 products, oleate and palmitoleate, have different metabolic properties. Palmitoleate reduces hepatic lipogenesis and improves insulin sensitivity, while oleate promotes ectopic fat accumulation and increases glucose intolerance. Hepatic oleate, but not palmitoleate, regulates body weight. Exercise increases SCD1 activity in skeletal muscle, indicating increased fatty acid synthesis, and is proposed to be protective against weight gain
physiological function
stearoyl-coenzyme A desaturase 1 (SCD1) is a central regulator of fuel metabolism. SCD1 catalyzes the synthesis of monounsaturated fatty acids (MUFAs), mainly oleate and palmitoleate, which are important in controlling weight gain in response to feeding high carbohydrate diets, role of SCD1 isoform in the regulation of lipid and glucose metabolism in metabolic tissues. SCD1 products, oleate and palmitoleate, have different metabolic properties. Palmitoleate reduces hepatic lipogenesis and improves insulin sensitivity, while oleate promotes ectopic fat accumulation and increases glucose intolerance. Hepatic oleate, but not palmitoleate, regulates body weight. Exercise increases SCD1 activity in skeletal muscle, indicating increased fatty acid synthesis, and is proposed to be protective against weight gain
additional information
-
a second transmembrane domain integrated in the membrane seems to be critical for desaturase activity
additional information
in SCD3, Ile112, Glu113, Ser292 and Met293 line the distal end of the substrate binding channel, Val119 is near the position of double bond formation, while Asp281 and Pro282 are on the cytoplasmic surface opposite to the CoA binding site
additional information
in SCD3, Ile112, Glu113, Ser292 and Met293 line the distal end of the substrate binding channel, Val119 is near the position of double bond formation, while Asp281 and Pro282 are on the cytoplasmic surface opposite to the CoA binding site
additional information
-
in SCD3, Ile112, Glu113, Ser292 and Met293 line the distal end of the substrate binding channel, Val119 is near the position of double bond formation, while Asp281 and Pro282 are on the cytoplasmic surface opposite to the CoA binding site
additional information
lipid and ceramide content analysis in untreated and inhibitor-treated ARPE-19 cells, overview
additional information
stearoyl-CoA desaturase-1 (SCD1) expression level significantly decreases in the kidneys of high-fat diet (HFD)-induced diabetic mice, compared with non-diabetic mice
additional information
structure-function analysis and catalytic mechanism of SCD-1, overview. SCD-1 consists of a cytosolic domain containing a di-metal active center and four alpha-helices forming a tight hydrophobic core, which is situated in the endoplasmic reticulum membrane. Acyl-CoA substrates bind to the surface of the cytoplasmic domain by forming multiple hydrogen bonds via the adenosine group, the panthothenate group and the carbonyl-group of the fatty acid. The substrate is fixed by ionic interactions between the phosphates of CoA and a positively charged surface of the enzyme and by a cation-Pi-interaction between adenosine and Lys194. The acyl-chain enters a hydrophobic tunnel extending to the interface of the cytoplasmic and transmembrane domain. The substrate tunnel has a kink, which is considered to hold the substrate and thereby determining regiospecificity of the enzyme and cis-conformation of the product. The catalytic center for dehydrogenation is located adjacent to the kink in the hydrophobic tunnel and adjacent to carbons 9 and 10 of stearoyl-CoA
additional information
structure-function analysis and catalytic mechanism of SCD-1, overview. SCD-1 consists of a cytosolic domain containing a di-metal active center and four alpha-helices forming a tight hydrophobic core, which is situated in the endoplasmic reticulum membrane. Acyl-CoA substrates bind to the surface of the cytoplasmic domain by forming multiple hydrogen bonds via the adenosine group, the panthothenate group and the carbonyl-group of the fatty acid. The substrate is fixed by ionic interactions between the phosphates of CoA and a positively charged surface of the enzyme and by a cation-Pi-interaction between adenosine and Lys194. The acyl-chain enters a hydrophobic tunnel extending to the interface of the cytoplasmic and transmembrane domain. The substrate tunnel has a kink, which is considered to hold the substrate and thereby determining regiospecificity of the enzyme and cis-conformation of the product. The catalytic center for dehydrogenation is located adjacent to the kink in the hydrophobic tunnel and adjacent to carbons 9 and 10 of stearoyl-CoA. Active site structure
additional information
the structure of isozyme SCD1 shows a fold comprising four transmembrane helices capped by a cytosolic domain, and a plausible pathway for lateral substrate access and product egress. The acyl chain of the bound stearoyl-CoA is enclosed in a tunnel buried in the cytosolic domain, and the geometry of the tunnel and configuration of the bound acyl chain provide a structural basis for the regioselectivity and stereospecificity of the desaturation reaction. The dimetal center is coordinated by a unique configuration of nine conserved histidine residues that implies a potentially distinct metal center and mechanism for oxygen activation, isozyme SCD1 structure analysis and modelling, overview. In SCD1, Ala108, Leu109, Ala288 and Val289 line the distal end of the substrate binding channel, Ala115 is near the position of double bond formation, while Gln277 and Ser278 are on the cytoplasmic surface opposite to the CoA binding site. Structural role of Arg249
additional information
the structure of isozyme SCD1 shows a fold comprising four transmembrane helices capped by a cytosolic domain, and a plausible pathway for lateral substrate access and product egress. The acyl chain of the bound stearoyl-CoA is enclosed in a tunnel buried in the cytosolic domain, and the geometry of the tunnel and configuration of the bound acyl chain provide a structural basis for the regioselectivity and stereospecificity of the desaturation reaction. The dimetal center is coordinated by a unique configuration of nine conserved histidine residues that implies a potentially distinct metal center and mechanism for oxygen activation, isozyme SCD1 structure analysis and modelling, overview. In SCD1, Ala108, Leu109, Ala288 and Val289 line the distal end of the substrate binding channel, Ala115 is near the position of double bond formation, while Gln277 and Ser278 are on the cytoplasmic surface opposite to the CoA binding site. Structural role of Arg249
additional information
-
the structure of isozyme SCD1 shows a fold comprising four transmembrane helices capped by a cytosolic domain, and a plausible pathway for lateral substrate access and product egress. The acyl chain of the bound stearoyl-CoA is enclosed in a tunnel buried in the cytosolic domain, and the geometry of the tunnel and configuration of the bound acyl chain provide a structural basis for the regioselectivity and stereospecificity of the desaturation reaction. The dimetal center is coordinated by a unique configuration of nine conserved histidine residues that implies a potentially distinct metal center and mechanism for oxygen activation, isozyme SCD1 structure analysis and modelling, overview. In SCD1, Ala108, Leu109, Ala288 and Val289 line the distal end of the substrate binding channel, Ala115 is near the position of double bond formation, while Gln277 and Ser278 are on the cytoplasmic surface opposite to the CoA binding site. Structural role of Arg249