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Literature summary for 1.14.19.17 extracted from
- Inhibitors of dihydroceramide desaturase 1 Therapeutic agents and pharmacological tools to decipher the role of dihydroceramides in cell biology (2016), Chem. Phys. Lipids, 197, 33-44 .
Application
| Application | Comment | Organism |
|---|---|---|
| drug development | Des1 is a potential therapeutic target for combating HIV-1 infection | Homo sapiens |
Cloned(Commentary)
| Cloned (Comment) | Organism |
|---|---|
| gene degs-1, recombinant expression in Escherichia coli and in 293-T cells | Homo sapiens |
| gene degs-1, recombinnat expression in Escherichia coli and in 293-T cells | Rattus norvegicus |
Protein Variants
| Protein Variants | Comment | Organism |
|---|---|---|
| additional information | generation of DES1 knockout mice | Mus musculus |
Inhibitors
| Inhibitors | Comment | Organism | Structure |
|---|---|---|---|
| 4-[[4-(4-chlorophenyl)-2-thiazolyl]amino]phenol | i.e. dual sphingosine kinase 1-2 inhibitor SKI II, a noncompetitive inhibitor of Des1 activity, molecular modeling studies | Homo sapiens |  |
| celecoxib | i.e. 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide. Celecoxib induces apoptosis and autophagy in gastric cancer cells through the phosphatidylinositol 3-kinase B signaling pathway | Homo sapiens | |
| celecoxib | i.e. 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide | Mus musculus | |
| celecoxib | i.e. 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide | Rattus norvegicus | |
| curcumin | i.e. (1E,6E)-1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione. Curcumin caused a 28% inhibition of Des 1 activity in human gastric adenocarcinoma HGC27 cell lysates at 0.01 mM. Physiological effects, detailed overview | Homo sapiens | |
| DELTA9-tetrahydrocannabinol | i.e. (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6 H-benzo[c]chromen-1-ol or THC, physiological effects, detailed overview | Homo sapiens | |
| DELTA9-tetrahydrocannabinol | i.e. (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6 H-benzo[c]chromen-1-ol or THC | Mus musculus | |
| DELTA9-tetrahydrocannabinol | i.e. (6aR,10aR)-6,6,9-trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6 H-benzo[c]chromen-1-ol or THC | Rattus norvegicus | |
| fenretinide | i.e. N-(4-hydroxyphenyl) retinamide or 4-HPR, a synthetic derivate of all-trans-retinoic acid, 4-HPR inhibition of Des1 might occur indirectly through increased oxidative species in vivo, but Des1 is a direct in vitro target for 4-HPR, which provokes an irreversible inhibition upon long incubation times. Inhibition mechanism, overview | Homo sapiens | |
| fenretinide | i.e. N-(4-hydroxyphenyl) retinamide or 4-HPR, a synthetic derivate of all-trans-retinoic acid, 4-HPR inhibition of Des1 might occur indirectly through increased oxidative species in vivo, but Des1 is a direct in vitro target for 4-HPR, which provokes an irreversible inhibition upon long incubation times. Inhibition mechanism, overview | Mus musculus | |
| fenretinide | i.e. N-(4-hydroxyphenyl) retinamide or 4-HPR, a synthetic derivate of all-trans-retinoic acid, 4-HPR inhibition of Des1 might occur indirectly through increased oxidative species in vivo, but Des1 is a direct in vitro target for 4-HPR, which provokes an irreversible inhibition upon long incubation times. Inhibition mechanism, overview | Rattus norvegicus | |
| gamma-tocopherol | i.e. (2 R)-2,7,8-trimethyl-2-[(4 R,8 R)-4,8,12-trimethyltridecyl]-6-chromanol, a natural component of vitamin E | Homo sapiens | |
| gamma-tocotrienol | i.e. (R)-gamma-tocotrienol or [R-(E,E)]-3,4-dihydro-2,7,8-trimethyl-2-(4,8,12-trimethyl-3,7,11-tridecatrienyl)-2 H-1-benzopyran-6-ol, a natural component of vitamin E | Homo sapiens | |
| GT11 | i.e. C8-cyclopropenylceramide, competitive inhibition, is active both in vitro and in intact cells | Homo sapiens | |
| GT11 | - |
Mus musculus | |
| GT11 | - |
Rattus norvegicus | |
| N-((2S,3S)-3-fluoro-1-hydroxydodecan-2-yl)acetamide | - |
Rattus norvegicus | |
| N-((2S,3S)-3-fluoro-1-hydroxydodecan-2-yl)hexanamide | - |
Rattus norvegicus | |
| N-[(2S,3R)-4-(2-hexylcyclopropyl)-1,3-dihydroxybutan-2-yl]dodecanamide | - |
Rattus norvegicus | |
| resveratrol | 3,5,4'-trihydroxy-trans-stilbene | Homo sapiens | |
| resveratrol | 3,5,4'-trihydroxy-trans-stilbene | Mus musculus | |
| resveratrol | 3,5,4'-trihydroxy-trans-stilbene | Rattus norvegicus | |
| XM462 | a 5-thiadihydroceramide, enzyme mechanism-based inhibitor. XM462 has been used as a pharmacological tool to show the role of dhCer as inducer of autophagy in human gastric cancer cell line HGC27 | Homo sapiens | |
| XM462 | a 5-thiadihydroceramide, enzyme mechanism-based inhibitor | Mus musculus | |
| XM462 | a 5-thiadihydroceramide, enzyme mechanism-based inhibitor | Rattus norvegicus | |
Localization
| Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|
| endoplasmic reticulum membrane | - |
Drosophila melanogaster | 5789 | - |
| endoplasmic reticulum membrane | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane | Homo sapiens | 5789 | - |
| endoplasmic reticulum membrane | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane | Mus musculus | 5789 | - |
| endoplasmic reticulum membrane | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane | Drosophila melanogaster | 5789 | - |
| endoplasmic reticulum membrane | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane | Rattus norvegicus | 5789 | - |
| microsome | - |
Mus musculus | - |
- |
| microsome | - |
Rattus norvegicus | - |
- |
| mitochondrial outer membrane | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane | Homo sapiens | 5741 | - |
| mitochondrial outer membrane | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane | Mus musculus | 5741 | - |
| mitochondrial outer membrane | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane | Drosophila melanogaster | 5741 | - |
| mitochondrial outer membrane | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane | Rattus norvegicus | 5741 | - |
Metals/Ions
| Metals/Ions | Comment | Organism | Structure |
|---|---|---|---|
| Fe2+ | required for the catalytic reaction, oscillates from Fe2+ to Fe3+, bound to the enzyme and to cofactor cytochrome b5 | Drosophila melanogaster | |
| Fe2+ | required for the catalytic reaction, oscillates from Fe2+ to Fe3+, bound to the enzyme and to cofactor cytochrome b5 | Homo sapiens | |
| Fe2+ | required for the catalytic reaction, oscillates from Fe2+ to Fe3+, bound to the enzyme and to cofactor cytochrome b5 | Mus musculus | |
| Fe2+ | required for the catalytic reaction, oscillates from Fe2+ to Fe3+, bound to the enzyme and to cofactor cytochrome b5 | Rattus norvegicus | |
Natural Substrates/ Products (Substrates)
| Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ | Drosophila melanogaster | - |
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ | Homo sapiens | - |
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ | Mus musculus | - |
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ | Rattus norvegicus | - |
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| additional information | Drosophila melanogaster | while Des1 exhibits high dihydroceramide C4-desaturase and very low C-4 hydroxylase activities, Des2, the product of the gene DEGS2 or DES2, exhibits bifunctional sphingolipid C-4 hydroxylase and C4-desaturase activities | ? | - |
? | |
Organism
| Organism | UniProt | Comment | Textmining |
|---|---|---|---|
| Drosophila melanogaster | - |
- |
- |
| Drosophila melanogaster | Q94515 | - |
- |
| Homo sapiens | O15121 | - |
- |
| Mus musculus | O09005 | - |
- |
| Rattus norvegicus | Q5XIF5 | - |
- |
Posttranslational Modification
| Posttranslational Modification | Comment | Organism |
|---|---|---|
| lipoprotein | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane, where it causes an increase in ceramide levels that in turn leads to apoptosis | Homo sapiens |
| lipoprotein | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane, where it causes an increase in ceramide levels that in turn leads to apoptosis | Mus musculus |
| lipoprotein | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane, where it causes an increase in ceramide levels that in turn leads to apoptosis | Drosophila melanogaster |
| lipoprotein | myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane, where it causes an increase in ceramide levels that in turn leads to apoptosis | Rattus norvegicus |
Reaction
| Reaction | Comment | Organism | Reaction ID |
|---|---|---|---|
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | FAD takes electrons from NADH and delivers them to ferrocytochrome b5 with bound Fe3+, which is converted to ferricytochrome b5 with Fe2+. Cytochrome b5-Fe2+ passes the electrons to another enzyme-bound Fe3+ to reduce O2 and form ceramide from dihydroceramide | Drosophila melanogaster | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | the desaturation reaction catalyzed by Des1 is presumably initiated by an enzyme-bound iron-oxo species that abstracts specifically the C-4 pro (R)-hydrogen atom from the substrate. FAD takes electrons from NADH and delivers them to ferrocytochrome b5 with bound Fe3+, which is converted to ferricytochrome b5 with Fe2+. Cytochrome b5-Fe2+ passes the electrons to another enzyme-bound Fe3+ to reduce O2 and form ceramide from dihydroceramide | Homo sapiens | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | the desaturation reaction catalyzed by Des1 is presumably initiated by an enzyme-bound iron-oxo species that abstracts specifically the C-4 pro (R)-hydrogen atom from the substrate. FAD takes electrons from NADH and delivers them to ferrocytochrome b5 with bound Fe3+, which is converted to ferricytochrome b5 with Fe2+. Cytochrome b5-Fe2+ passes the electrons to another enzyme-bound Fe3+ to reduce O2 and form ceramide from dihydroceramide | Mus musculus | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | the desaturation reaction catalyzed by Des1 is presumably initiated by an enzyme-bound iron-oxo species that abstracts specifically the C-4 pro (R)-hydrogen atom from the substrate. FAD takes electrons from NADH and delivers them to ferrocytochrome b5 with bound Fe3+, which is converted to ferricytochrome b5 with Fe2+. Cytochrome b5-Fe2+ passes the electrons to another enzyme-bound Fe3+ to reduce O2 and form ceramide from dihydroceramide | Drosophila melanogaster | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ = a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | the desaturation reaction catalyzed by Des1 is presumably initiated by an enzyme-bound iron-oxo species that abstracts specifically the C-4 pro (R)-hydrogen atom from the substrate. FAD takes electrons from NADH and delivers them to ferrocytochrome b5 with bound Fe3+, which is converted to ferricytochrome b5 with Fe2+. Cytochrome b5-Fe2+ passes the electrons to another enzyme-bound Fe3+ to reduce O2 and form ceramide from dihydroceramide | Rattus norvegicus |
Source Tissue
| Source Tissue | Comment | Organism | Textmining |
|---|---|---|---|
| A3 cell | - |
Homo sapiens | - |
| breast cancer cell | - |
Homo sapiens | - |
| gastric cancer cell | - |
Homo sapiens | - |
| glioma cell | - |
Homo sapiens | - |
| HGC-27 cell | - |
Homo sapiens | - |
| liver | - |
Rattus norvegicus | - |
| MCF-7 cell | - |
Homo sapiens | - |
| MDA-MB-231 cell | - |
Homo sapiens | - |
| additional information | Des1 is expressed in multiple tissues | Homo sapiens | - |
| Mueller cell | - |
Homo sapiens | - |
| retina | within the neural retina, Des1 is expressed in Müller cells, the site of the proposed alternative visual cycle. Des1 is also expressed in the retinal pigment epithelium, where it may augment synthesis of cis-11-retinol | Homo sapiens | - |
| U-373MG cell | - |
Homo sapiens | - |
| U87-MG cell | - |
Homo sapiens | - |
Substrates and Products (Substrate)
| Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ | - |
Drosophila melanogaster | a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ | - |
Homo sapiens | a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ | - |
Mus musculus | a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+ | - |
Rattus norvegicus | a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O | - |
? | |
| additional information | while Des1 exhibits high dihydroceramide C4-desaturase and very low C-4 hydroxylase activities, Des2, the product of the gene DEGS2 or DES2, exhibits bifunctional sphingolipid C-4 hydroxylase and C4-desaturase activities | Drosophila melanogaster | ? | - |
? | |
| additional information | the electron provided by NAD(P)H is sequentially transported from the cofactor to NADH-cytochrome b5 reductase, cytochrome b5, and the terminal desaturase, which reduces oxygen to water and oxidizes dihydroceramide to ceramide. Desaturation of the D-erythro-isomer by Des1 is much faster than that of the L or D-threo-isomers | Homo sapiens | ? | - |
? | |
| additional information | the electron provided by NAD(P)H is sequentially transported from the cofactor to NADH-cytochrome b5 reductase, cytochrome b5, and the terminal desaturase, which reduces oxygen to water and oxidizes dihydroceramide to ceramide. Desaturation of the D-erythro-isomer by Des1 is much faster than that of the L or D-threo-isomers | Mus musculus | ? | - |
? | |
| additional information | the electron provided by NAD(P)H is sequentially transported from the cofactor to NADH-cytochrome b5 reductase, cytochrome b5, and the terminal desaturase, which reduces oxygen to water and oxidizes dihydroceramide to ceramide. Desaturation of the D-erythro-isomer by Des1 is much faster than that of the L or D-threo-isomers | Drosophila melanogaster | ? | - |
? | |
| additional information | the electron provided by NAD(P)H is sequentially transported from the cofactor to NADH-cytochrome b5 reductase, cytochrome b5, and the terminal desaturase, which reduces oxygen to water and oxidizes dihydroceramide to ceramide. Desaturation of the D-erythro-isomer by Des1 is much faster than that of the L or D-threo-isomers | Rattus norvegicus | ? | - |
? | |
Synonyms
| Synonyms | Comment | Organism |
|---|---|---|
| Degs1 | - |
Homo sapiens |
| Degs1 | - |
Mus musculus |
| Degs1 | - |
Drosophila melanogaster |
| Degs1 | - |
Rattus norvegicus |
| DEGS2 | - |
Drosophila melanogaster |
| DES1 | - |
Homo sapiens |
| DES1 | - |
Mus musculus |
| DES1 | - |
Drosophila melanogaster |
| DES1 | - |
Rattus norvegicus |
| DES2 | - |
Drosophila melanogaster |
| dihydroceramide C4-desaturase | - |
Drosophila melanogaster |
| dihydroceramide C4-desaturase | - |
Homo sapiens |
| dihydroceramide C4-desaturase | - |
Mus musculus |
| dihydroceramide C4-desaturase | - |
Rattus norvegicus |
| dihydroceramide desaturase 1 | - |
Homo sapiens |
| dihydroceramide desaturase 1 | - |
Mus musculus |
| dihydroceramide desaturase 1 | - |
Drosophila melanogaster |
| dihydroceramide desaturase 1 | - |
Rattus norvegicus |
| dihydroceramide desaturase 2 | - |
Drosophila melanogaster |
| drosophila degenerative spermatocyte 1 | - |
Homo sapiens |
| drosophila degenerative spermatocyte 1 | - |
Mus musculus |
| drosophila degenerative spermatocyte 1 | - |
Drosophila melanogaster |
| drosophila degenerative spermatocyte 1 | - |
Rattus norvegicus |
| drosophila degenerative spermatocyte 2 | - |
Drosophila melanogaster |
pH Optimum
| pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|
| 8.5 | - |
- |
Drosophila melanogaster |
| 8.5 | - |
- |
Homo sapiens |
| 8.5 | - |
- |
Mus musculus |
| 8.5 | - |
- |
Rattus norvegicus |
pH Range
| pH Minimum | pH Maximum | Comment | Organism |
|---|---|---|---|
| 6.5 | 9 | activity range | Drosophila melanogaster |
| 6.5 | 9 | activity range | Homo sapiens |
| 6.5 | 9 | activity range | Mus musculus |
| 6.5 | 9 | activity range | Rattus norvegicus |
Cofactor
| Cofactor | Comment | Organism | Structure |
|---|---|---|---|
| cytochrome b5 | - |
Drosophila melanogaster | |
| cytochrome b5 | - |
Homo sapiens | |
| cytochrome b5 | - |
Mus musculus | |
| cytochrome b5 | - |
Rattus norvegicus | |
| FAD | - |
Drosophila melanogaster | |
| FAD | - |
Homo sapiens | |
| FAD | - |
Mus musculus | |
| FAD | - |
Rattus norvegicus | |
| NAD(P)H | Des1 requires NADPH or NADH as electron donor and oxygen as electron acceptor | Homo sapiens | |
| NAD(P)H | Des1 requires NADPH or NADH as electron donor and oxygen as electron acceptor | Mus musculus | |
| NAD(P)H | Des1 requires NADPH or NADH as electron donor and oxygen as electron acceptor | Rattus norvegicus | |
| NADH | - |
Drosophila melanogaster | |
Ki Value [mM]
| Ki Value [mM] | Ki Value maximum [mM] | Inhibitor | Comment | Organism | Structure |
|---|---|---|---|---|---|
| 0.0003 | - |
4-[[4-(4-chlorophenyl)-2-thiazolyl]amino]phenol | pH and temperature not specified in the publication | Homo sapiens | |
| 0.006 | - |
GT11 | pH and temperature not specified in the publication | Homo sapiens | |
IC50 Value
| IC50 Value | IC50 Value Maximum | Comment | Organism | Inhibitor | Structure |
|---|---|---|---|---|---|
| 0.000023 | - |
pH and temperature not specified in the publication | Homo sapiens | GT11 | |
| 0.00043 | - |
pH and temperature not specified in the publication, Jurkat A3 cells | Homo sapiens | XM462 | |
| 0.0082 | - |
pH and temperature not specified in the publication, rat liver microsomes | Rattus norvegicus | XM462 | |
| 0.023 | - |
pH and temperature not specified in the publication | Rattus norvegicus | DELTA9-tetrahydrocannabinol | |
| 0.08 | - |
pH and temperature not specified in the publication | Homo sapiens | celecoxib | |
Expression
| Organism | Comment | Expression |
|---|---|---|
| Drosophila melanogaster | Des1 is upregulated under hypoxia | up |
| Homo sapiens | Des1 is upregulated under hypoxia. Upregulation of Des1 occurs by saturated fatty acids and anoxia | up |
| Rattus norvegicus | Des1 is upregulated under hypoxia. Upregulation of Des1 occurs by saturated fatty acids and anoxia | up |
| Drosophila melanogaster | Des2 is upregulated under hypoxia | up |
General Information
| General Information | Comment | Organism |
|---|---|---|
| malfunction | homozygous DES1-null mice are viable, they fail to thrive and have numerous health abnormalities, dying within the first 8-weeks of age. In contrast, the heterozygous mice are viable with normal Mendelian birth rates. Lipid analysis reveal that DES1 heterozygous mice show higher dhCer/Cer ratios in multiple organs. Importantly, these mice are protected from glucocorticoid-, saturated fat- and obesity-induced insulin resistance, as well as from diet-induced hypertension. Cells from DES1 null mice are resistant to apoptosis, and, although they exhibit a remarkably strong activation of protein kinase B, they show high levels of autophagy. The latter results from activation of AMP-activated protein kinase. Therefore, ablation of DES1 simultaneously stimulates anabolic and catabolic signaling through activation of protein kinase B and AMP-activated protein kinase pathways, respectively. Activation of pro-survival and anabolic signaling intermediates provided protection from apoptosis caused by etoposide. Heterozygous deletion of DES1 prevented vascular dysfunction and hypertension in mice after high-fat feeding | Mus musculus |
| metabolism | the enzyme catalyzes the oxidation of dhCer to ceramide (Cer) by dihydroceramide desaturase 1 (Des1), the last step of the de novo sphingolipids biosynthetic pathway. Ceramides, and, to a lesser extent, dihydroceramides are further metabolized to complex sphingolipids, such as (dihydro) sphingomyelins and (dihydro) glycosphingolipids by other enzymes | Homo sapiens |
| metabolism | the enzyme catalyzes the oxidation of dhCer to ceramide (Cer) by dihydroceramide desaturase 1 (Des1), the last step of the de novo sphingolipids biosynthetic pathway. Ceramides, and, to a lesser extent, dihydroceramides are further metabolized to complex sphingolipids, such as (dihydro) sphingomyelins and (dihydro) glycosphingolipids by other enzymes | Mus musculus |
| metabolism | the enzyme catalyzes the oxidation of dhCer to ceramide (Cer) by dihydroceramide desaturase 1 (Des1), the last step of the de novo sphingolipids biosynthetic pathway. Ceramides, and, to a lesser extent, dihydroceramides are further metabolized to complex sphingolipids, such as (dihydro) sphingomyelins and (dihydro) glycosphingolipids by other enzymes | Drosophila melanogaster |
| metabolism | the enzyme catalyzes the oxidation of dhCer to ceramide (Cer) by dihydroceramide desaturase 1 (Des1), the last step of the de novo sphingolipids biosynthetic pathway. Ceramides, and, to a lesser extent, dihydroceramides are further metabolized to complex sphingolipids, such as (dihydro) sphingomyelins and (dihydro) glycosphingolipids by other enzymes | Rattus norvegicus |
| metabolism | the enzyme catalyzes the oxidation of dhCer to ceramide (Cer) by dihydroceramide desaturase 1 (Des1), the last step of the de novo sphingolipids biosynthetic pathway. Ceramides, and, to a lesser extent, dihydroceramides are further metabolized to complex sphingolipids, such as (dihydro)sphingomyelins and (dihydro)glycosphingolipids by other enzymes | Drosophila melanogaster |
| physiological function | dihydroceramide desaturase (Des1) is the last enzyme in the de novo synthesis of ceramides (Cer). It catalyzes the insertion of a double bond into dihydroceramides (dhCer) to convert them to Cer, both of which are further metabolized to more complex (dihydro) sphingolipids. Dihydroceramides are implicated in a wide spectrum of biological processes. Des1 is regulated by fatty acids, myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane, where it causes an increase in ceramide levels that in turn leads to apoptosis | Mus musculus |
| physiological function | dihydroceramide desaturase (Des1) is the last enzyme in the de novo synthesis of ceramides (Cer). It catalyzes the insertion of a double bond into dihydroceramides (dhCer) to convert them to Cer, both of which are further metabolized to more complex (dihydro) sphingolipids. Dihydroceramides are implicated in a wide spectrum of biological processes. Des1 is regulated by fatty acids, myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane, where it causes an increase in ceramide levels that in turn leads to apoptosis | Rattus norvegicus |
| physiological function | dihydroceramide desaturase (Des1) is the last enzyme in the de novo synthesis of ceramides (Cer). It catalyzes the insertion of a double bond into dihydroceramides (dhCer) to convert them to Cer, both of which are further metabolized to more complex (dihydro) sphingolipids. Dihydroceramides are implicated in a wide spectrum of biological processes. Des1 is regulated by fatty acids, myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane, where it causes an increase in ceramide levels that in turn leads to apoptosis. Des1 is upregulated under hypoxia to cope with the decreased enzyme activity and the consequent raise in dhCer production. By producing (cis)-9-retinol, which can be readily converted to (cis)-9-retinoic acid, Des1 is the only known source of 9-cis-retinoids in vertebrates | Drosophila melanogaster |
| physiological function | dihydroceramide desaturase (Des1) is the last enzyme in the de novo synthesis of ceramides (Cer). It catalyzes the insertion of a double bond into dihydroceramides (dhCer) to convert them to Cer, both of which are further metabolized to more complex (dihydro) sphingolipids. Dihydroceramides are implicated in a wide spectrum of biological processes. Des1 is regulated by fatty acids, myristoylation of Des1 increases the enzyme activity and alters its subcellular localization, targeting the enzyme from the endoplasmic reticulum to the mitochondrial outer membrane, where it causes an increase in ceramide levels that in turn leads to apoptosis. Des1 is upregulated under hypoxia to cope with the decreased enzyme activity and the consequent raise in dhCer production. Des1 is also expressed in the retinal pigment epithelium, where it may augment synthesis of cis-11-retinol. By producing (cis)-9-retinol, which can be readily converted to (cis)-9-retinoic acid, Des1 is the only known source of 9-cis-retinoids in vertebrates. Des1, by means of its isomerase-2 activity, may play a role in nonvisual processes such as cell growth, differentiation, apoptosis and malignant transformation by contributing to the synthesis of (cis)-9-retinoic acid. Addition of all-trans-retinol to Des 1-expressing 293T cell homogenates or to purified Des1 expressed in Escherichia coli results in the formation of (cis)-11-retinol, (cis,cis)-9,13-retinol, (cis)-9-retinol and (cis)-13-retinol at ratios similar to those seen after iodine-catalyzed retinoid equilibration. The rate of Des1-catalyzed retinol equilibration is very high | Homo sapiens |
| physiological function | dihydroceramide desaturase (Des1) is the last enzyme in the de novo synthesis of ceramides (Cer). It catalyzes the insertion of a double bond into dihydroceramides (dhCer) to convert them to Cer, both of which are further metabolized to more complex (dihydro)sphingolipids. Dihydroceramides are implicated in a wide spectrum of biological processes. Des2 is upregulated under hypoxia to cope with the decreased enzyme activity and the consequent raise in dhCer production | Drosophila melanogaster |
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Release 2023.1 (January 2023)
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