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Literature summary for 1.14.19.1 extracted from
- Stearoyl-CoA desaturase-1 and adaptive stress signaling (2016), Biochim. Biophys. Acta, 1861, 1719-1726 .
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | SCD-1 is a promising target for the treatment of cancer, skin disorders and metabolic diseases, development of clinical drug candidates | Mus musculus |
| drug development | SCD-1 is a promising target for the treatment of cancer, skin disorders and metabolic diseases, development of clinical drug candidates | Homo sapiens |
Crystallization (Commentary)
| Crystallization (Comment) | Organism |
|---|---|
| purified enzyme in complex with its substrate stearoyl-CoA, X-ray diffraction structure determination and analysis at 3.25 A resolution. The two iron cations are replaced by zinc cations in the crystal structure | Homo sapiens |
| purified free enzyme, X-ray diffraction structure determination and analysis at 2.6 A resolution. The two iron cations are replaced by zinc cations in the crystal structure | Mus musculus |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| endoplasmic reticulum membrane | - |
Mus musculus | 5789 | - |
| endoplasmic reticulum membrane | - |
Homo sapiens | 5789 | - |
| additional information | 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 | Mus musculus | - |
- |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Fe2+ | SCD-1 has a di-metal catalytic center consisting of two iron cations (in the crystal structures replaced by zinc cations) that are coordinated by histidine residues and a single water molecule | Mus musculus |  |
| Fe2+ | SCD-1 has a di-metal catalytic center consisting of two iron cations (in the crystal structures replaced by zinc cations) that are coordinated by histidine residues and a single water molecule | Homo sapiens | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| palmitoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ | Mus musculus | - |
palmitoleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| palmitoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ | Homo sapiens | - |
palmitoleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ | Mus musculus | - |
oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ | Homo sapiens | - |
oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Homo sapiens | O00767 | - |
- |
| Mus musculus | P13516 | - |
- |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ = oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | the DELTA9-desaturase SCD-1 introduces a cis-double bond into saturated fatty acids between carbons 9 and 10. Preferred substrates of SCD-1 are long-chain acyl-CoAs with 13 to 19 carbons, among them stearoyl-CoA and palmitoyl-CoA, the most abundant saturated fatty acid-CoA ester in mammalians. Dehydrogenation of the pro-R hydrogens at C9 and C10 requires molecular oxygen which is activated at the di-iron center and reduced to water. Two of the electrons transferred to molecular oxygen derive from the acyl-CoA substrate and two others from the di-iron center. The ferrous catalytic center is regenerated by electron transfer from cytochrome b5, which has been suggested to bind to a groove at the cytoplasmic domain and to transmit electrons via two histidine residues (H157 and H298) bridging the distance. Ferrocytochrome b5 is provided by cytochrome b5 reductase using NAD(P)H as co-substrate | Homo sapiens | |
| stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ = oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | the DELTA9-desaturase SCD-1 introduces a cis-double bond into saturated fatty acids between carbons 9 and 10. Preferred substrates of SCD-1 are long-chain acyl-CoAs with 13 to 19 carbons, among them stearoyl-CoA and palmitoyl-CoA, the most abundant saturated fatty acid-CoA ester in mammalians. Dehydrogenation of the pro-R hydrogens at C9 and C10 requires molecular oxygen which is activated at the di-iron center and reduced to water. Two of the electrons transferred to molecular oxygen derive from the acyl-CoA substrate and two others from the di-iron center. The ferrous catalytic center is regenerated by electron transfer from cytochrome b5, which has been suggested to bind to a groove at the cytoplasmic domain and to transmit electrons via two histidine residues bridging the distance. Ferrocytochrome b5 is provided by cytochrome b5 reductase using NAD(P)H as co-substrate | Mus musculus |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| palmitoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ | - |
Mus musculus | palmitoleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| palmitoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ | - |
Homo sapiens | palmitoleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ | - |
Mus musculus | oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| stearoyl-CoA + 2 ferrocytochrome b5 + O2 + 2 H+ | - |
Homo sapiens | oleoyl-CoA + 2 ferricytochrome b5 + 2 H2O | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| SCD-1 | - |
Mus musculus |
| SCD-1 | - |
Homo sapiens |
| stearoyl-CoA desaturase-1 | - |
Mus musculus |
| stearoyl-CoA desaturase-1 | - |
Homo sapiens |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| cytochrome b5 | a redox-active co-substrate reducing molecular oxygen to water. Ferrocytochrome b5 is regenerated by reduction of ferricytochrome b5 through cyt. b5 reductase using NADPH as electron donor | Mus musculus | |
| cytochrome b5 | a redox-active co-substrate reducing molecular oxygen to water. Ferrocytochrome b5 is regenerated by reduction of ferricytochrome b5 through cyt. b5 reductase using NADPH as electron donor | Homo sapiens |
General Information
| General Information | Comment | Organism |
|---|---|---|
| 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 | Mus musculus |
| 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 | Homo sapiens |
| metabolism | survival and stress-activated signaling pathways are regulated by SCD-1, molecular link between SCD-1 activity and cell signaling, overview | Mus musculus |
| metabolism | survival and stress-activated signaling pathways are regulated by SCD-1, molecular link between SCD-1 activity and cell signaling, overview | Homo sapiens |
| 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 | Mus musculus |
| 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 | Homo sapiens |
| 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 | Mus musculus |
| 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 | Homo sapiens |
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Release 2023.1 (January 2023)
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