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2,4-dinitrophenyl-sphinganine + reduced acceptor + O2 + H+
2,4-dinitrophenyl-sphingosine + acceptor + H2O
-
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
dihydroceramide + reduced acceptor + O2 + H+
(4E)-sphing-4-enine ceramide + acceptor + H2O
-
-
-
-
?
dihydrosphingomyelin + NADH + O2 + H+
?
20% activity compared to N-octanoyl-D-erythro-C18-sphinganine
-
-
?
N-((2S,3R,6E)-1,3-dihydroxyoctadec-6-en-2-yl)-6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)hexanamide + 2 ferrocytochrome b5 + O2 + 2 H+
N-((2S,3R,4E,6E)-1,3-dihydroxyoctadeca-4,6-dien-2-yl)-6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)hexanamide + 2 ferricytochrome b5 + 2 H2O
-
-
-
-
?
N-((2S,3R,6E)-1,3-dihydroxyoctadec-6-en-2-yl)octanamide + 2 ferrocytochrome b5 + O2 + 2 H+
N-((2S,3R,4E,6E)-1,3-dihydroxyoctadeca-4,6-dien-2-yl)octanamide + 2 ferricytochrome b5 + 2 H2O
-
-
-
-
?
N-((2S,3R,6Z)-1,3-dihydroxyoctadec-6-en-2-yl)-6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)hexanamide + 2 ferrocytochrome b5 + O2 + 2 H+
N-((2S,3R,4E,6Z)-1,3-dihydroxyoctadeca-4,6-dien-2-yl)-6-((7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)amino)hexanamide + 2 ferricytochrome b5 + 2 H2O
-
-
-
-
?
N-((2S,3R,6Z)-1,3-dihydroxyoctadec-6-en-2-yl)octanamide + 2 ferrocytochrome b5 + O2 + 2 H+
N-((2S,3R,4E,6Z)-1,3-dihydroxyoctadeca-4,6-dien-2-yl)octanamide + 2 ferricytochrome b5 + 2 H2O
-
-
-
-
?
N-hexanoyl-[4,5-3H]sphinganine + NADPH + O2 + H+
?
-
-
-
?
N-octanoyl-D-erythro-C18-sphinganine + NADH + O2 + H+
N-octanoyl-D-erythro-C18-sphingosine + NAD+ + H2O
-
-
-
?
N-octanoyl-D-erythro-C18-sphinganine + NADPH + O2 + H+
N-octanoyl-D-erythro-C18-sphingosine + NADP+ + H2O
-
-
-
?
N-octanoyldihydroceramide + NAD(P)H + O2 + H+
?
-
-
-
?
N-octanoylsphinganine + ferrocytochrome b5 + O2 + 2 H+
N-octanoylsphingosine + ferricytochrome b5 + 2 H2O
-
-
-
-
?
N-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-D-erythro-sphinganine + 2 ferrocytochrome b5 + O2 + 2 H+
?
N-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-D-erythro-sphinganine + reduced acceptor + O2 + 2 H+
?
-
-
-
-
?
tetracosanoyl-dihydroceramide + reduced acceptor + O2 + 2 H+
?
-
-
-
-
?
additional information
?
-
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
N-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-D-erythro-sphinganine + 2 ferrocytochrome b5 + O2 + 2 H+
?
-
-
-
-
?
N-[6-[(7-nitro-2-1,3-benzoxadiazol-4-yl)amino]hexanoyl]-D-erythro-sphinganine + 2 ferrocytochrome b5 + O2 + 2 H+
?
-
fluorescence-lebeld substrate
-
-
?
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
-
-
?
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
-
-
?
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
-
-
?
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
-
-
?
additional information
?
-
-
configurational preference of dihydroceramide desaturase-1 towards DELTA6-unsaturated substrates. Establishment of an assay for Des1 activity based on the use of an immobilized DELTA6-monoene as a substrate for further click reaction of the resulting diene with a labelable dienophile, chemical synthesis of DELTA6 and DELTA4,6 sphingoid bases, substrate specificity, overview
-
-
?
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
-
-
?
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
-
-
?
additional information
?
-
no activity detected with dihydroglucosylceramide
-
-
?
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
-
-
?
additional information
?
-
the enzyme does not recognise fatty acids and trihydroxylated sphingoid long-chain bases as substrate
-
-
?
additional information
?
-
-
the enzyme does not recognise fatty acids and trihydroxylated sphingoid long-chain bases as substrate
-
-
?
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a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
dihydroceramide + reduced acceptor + O2 + H+
(4E)-sphing-4-enine ceramide + acceptor + H2O
-
-
-
-
?
tetracosanoyl-dihydroceramide + reduced acceptor + O2 + 2 H+
?
-
-
-
-
?
additional information
?
-
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
?
a dihydroceramide + 2 ferrocytochrome b5 + O2 + 2 H+
a (4E)-sphing-4-enine ceramide + 2 ferricytochrome b5 + 2 H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + H2O
-
-
-
?
dihydroceramide + ferrocytochrome b5 + O2 + H+
(4E)-sphing-4-enine ceramide + ferricytochrome b5 + 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
-
-
?
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
-
-
?
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(Z)-4-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)amino)-N-hydroxybenzimidamide
-
completely inhibits Des1 activity at 0.01 mM but shows little activity at 0.001 mM
2-(p-hydroxyanilino)-4-(p-chlorophenyl)thiazole
-
SKi, a SK1/SK2 inhibitor
3-(4-chlorophenyl)-adamantane-1-carboxylic acid (pyridin-4-ylmethyl)amide
-
i.e. ABC294640
4-((4-(4-chlorophenyl)thiazol-2-yl)amino)phenol
-
i.e. SKI-II, noncompetitive inhibitor of enzyme Des1, structure-activity relationship analysis, inhibition mechanism, overview
4-((5-(4-iodophenyl)-1,3,4-oxadiazol-2-yl)amino)phenol
-
-
4-oxo-N-(4-hydroxyphenyl)retinamide
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
5-(4-chlorophenyl)-N-(4-hydroxyphenyl)-1,3,4-oxadiazol-2-amine
-
-
alpha-cyclodextrin
18% residual activity at a substrate/cyclodextrin molar ratio of 0.5
ascorbic acid
inhibitory at high concentrations
beta-cyclodextrin
20% residual activity at a substrate/cyclodextrin molar ratio of 0.5
Brij-35
13% residual activity at 0.1 mM
CHAPS
3.0% residual activity at 6.5 mM
Cu2+
25% inhibition at 1 mM
decylmaltoside
27% residual activity at 1.6 mM
DELTA9-tetrahydrocannabinol
dithiothreitol
81% inhibition at 1 mM
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
lauryl-N,N-dimethylamine
28% residual activity at 2.1 mM
N-((2S,3R,6E)-1,3-dihydroxyoctadec-6-en-2-yl)octanamide
-
substrate inhibition, non-competitive type of inhibition
N-((2S,3R,6Z)-1,3-dihydroxyoctadec-6-en-2-yl)octanamide
-
substrate inhibition
N-((2S,3S)-3-fluoro-1-hydroxydodecan-2-yl)acetamide
-
N-((2S,3S)-3-fluoro-1-hydroxydodecan-2-yl)hexanamide
-
N-dodecylsarcosine
complete inhibition at 14.6 mM
N-octyl-N,N-dimethyl-3-ammonio-1-propane sulfonate
18% residual activity at 330 mM
N-[(2S,3R)-4-(2-hexylcyclopropyl)-1,3-dihydroxybutan-2-yl]dodecanamide
-
octylglucoside
8.5% residual activity at 25 mM
SDS
0.3% residual activity at 0.24% (w/v)
SKI II
-
noncompetitive inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II, a dual inhibitor of sphingosine kinases (SKs) 1 and 2, overview. Use of SKI II in the context of cancer therapy
sucrose monolaurate
27% residual activity at 0.2 mM
Thesit
23% residual activity at 0.1 mM
-
Triton X-100
13% residual activity at 0.25 mM
4-oxo-N-(4-hydroxyphenyl)retinamide
-
4-oxo-N-(4-hydroxyphenyl)retinamide
leads to an increase in C16 and C18 dihydroceramide substrate accumulation
celecoxib
-
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
celecoxib
i.e. 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
celecoxib
i.e. 4-[5-(4-methylphenyl)-3-(trifluoromethyl)pyrazol-1-yl]benzenesulfonamide
curcumin
-
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
DELTA9-tetrahydrocannabinol
-
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
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
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
fenretinide
i.e. N-(4-hydroxyphenyl) retinamide, fenretinide directly targets and irreversibly inhibits DEGS1 in a time-dependent manner, by disrupting the electron transport necessary for desaturation
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
fenretinide
-
a direct inhibitor of Des1 that initially shows competitive inhibition but becomes an irreversible inhibitor over longer incubation times. The 4-aminophenol may play an important role in mediating its irreversible inhibition of Des1, where Des1 oxidation of this group generates a reactive iminoquinone intermediate that reacts with nucleophilic sites on the protein, leading to time-dependent irreversible inhibition of Des1, inhibition mechanism, overview
fenretinide
-
the Des1 inhibitor induces a reduction in SK1a expression and an increase in p53 and p21 expression
fenretinide
i.e. N-(4-hydroxyphenyl)retinamide, a synthetic retinoid, leads to an increase in C16 and C18 dihydroceramide substrate accumulation
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
fenretinide
i.e. N-(4-hydroxyphenyl)retinamide, a synthetic retinoid, leads to an increase in C16 and C18 dihydroceramide substrate accumulation
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
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
gamma-tocotrienol
a component of vitamin E, gammaTE, inhibits DEGS and decreases de novo ceramide synthesis, elevation of ceramides during prolonged gammaTE treatment is likely caused by sphingomeylinase-mediated hydrolysis of sphingomyelin
GT11
a cyclopropenylceramide (C8CCP) that acts in primary neuronal cultures as a potent specific and competitive inhibitor of DESG1 at concentrations up to 0.001 mM
GT11
i.e. C8-cyclopropenylceramide, competitive inhibition, is active both in vitro and in intact cells
resveratrol
-
resveratrol
3,5,4'-trihydroxy-trans-stilbene
resveratrol
3,5,4'-trihydroxy-trans-stilbene
resveratrol
3,5,4'-trihydroxy-trans-stilbene
XM462
-
XM462
-
an active-site directed Des1 inhibitor
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
XM462
a 5-thiadihydroceramide, enzyme mechanism-based inhibitor
XM462
a 5-thiadihydroceramide, enzyme mechanism-based inhibitor
additional information
-
in T98G and U87MG glioblastoma cell lines different Des1 inhibitory pro-autophagic compounds (DIPACS) exhibiting different cytotoxicities (CCX, PXD, resveratrol, gamma-tocotrienol and XM462), trigger autophagy via different pathways, both dihydroceramide-dependent and independent pathways
-
additional information
-
DELTA6-monoenoic ceramide inhibit Des1
-
additional information
-
no inhibition by (2S,3S)-2-((4-(3-(4-chlorophenyl)-1,2,4-oxadiazol-5-yl)benzyl)-carbamoyl)-3-hydroxypyrrolidin-1-ium, 4-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)phenol, (Z)-4-(5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)-N?-hydroxybenzimidamide, amino(4-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)amino)-phenyl)methaniminium, (E)-4-((5-(4-chlorophenyl)-1,3,4-oxadiazol-2-yl)amino)-benzaldehyde oxime, and 5-(4-chlorophenyl)-N-(pyridin-4-ylmethyl)-1,3,4-oxadiazol-2-amine
-
additional information
no inhibition of the enzyme by N-[4-methoxyphenyl]retinamide and by non-retinoid RBP4 ligand A1120, RBP4 is a serum retinol-binding protein. The presence of fenretinide or 4-oxo-N-(4-hydroxyphenyl)retinamide leads to 2.7 and 3fold increases in ratio for C16 and C18 ceramides ratio respectively
-
additional information
no inhibition of the enzyme by N-[4-methoxyphenyl]retinamide and by non-retinoid RBP4 ligand A1120, RBP4 is a serum retinol-binding protein. The presence of fenretinide or 4-oxo-N-(4-hydroxyphenyl)retinamide leads to 2.7 and 3fold increases in ratio for C16 and C18 ceramides ratio respectively
-
additional information
not inhibited by EDTA and Na2SO4
-
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Alzheimer Disease
Dihydroceramide Desaturase 1 Inhibitors Reduce Amyloid-? Levels in Primary Neurons from an Alzheimer's Disease Transgenic Model.
Amyloidosis
Dihydroceramide Desaturase 1 Inhibitors Reduce Amyloid-? Levels in Primary Neurons from an Alzheimer's Disease Transgenic Model.
Asthma
Current status of allergy prevalence in Germany: Position paper of the Environmental Medicine Commission of the Robert Koch Institute.
Carcinogenesis
SLC14A1 prevents oncometabolite accumulation and recruits HDAC1 to transrepress oncometabolite genes in urothelial carcinoma.
Carcinoma
Dihydroceramide delays cell cycle G1/S transition via activation of ER stress and induction of autophagy.
Carcinoma
Overexpression of degenerative spermatocyte homolog 1 up-regulates the expression of cyclin D1 and enhances metastatic efficiency in esophageal carcinoma Eca109 cells.
Carcinoma, Non-Small-Cell Lung
The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells.
Carcinoma, Squamous Cell
Dihydroceramide desaturase knockdown impacts sphingolipids and apoptosis after photodamage in human head and neck squamous carcinoma cells.
Chickenpox
Vaccine-Preventable Infections in Childcare Workers.
Cholangiocarcinoma
Dihydroceramide desaturase activity in tumors.
Colorectal Neoplasms
M6A methylation of DEGS2, a key ceramide-synthesizing enzyme, is involved in colorectal cancer progression through ceramide synthesis.
Coronary Artery Disease
Second vs. first-generation drug-eluting stents in complex lesions subsets: 3 years' follow-up of ERACI IV study.
Coronary Disease
[Prevalence of myocardial infarction and coronary heart disease in adults aged 40-79 years in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1)].
Dermatitis, Atopic
Current status of allergy prevalence in Germany: Position paper of the Environmental Medicine Commission of the Robert Koch Institute.
Dermatitis, Contact
Current status of allergy prevalence in Germany: Position paper of the Environmental Medicine Commission of the Robert Koch Institute.
Diabetes Mellitus, Type 2
Lipid environment induces ER stress, TXNIP expression and inflammation in immune cells of individuals with type 2 diabetes.
Dystonia
Recent genetic advances in early-onset dystonia.
Food Hypersensitivity
Current status of allergy prevalence in Germany: Position paper of the Environmental Medicine Commission of the Robert Koch Institute.
Hepatitis A
Vaccine-Preventable Infections in Childcare Workers.
Herpes Zoster
Vaccine-Preventable Infections in Childcare Workers.
HIV Infections
Reconnaissance of the candidate genes involved in the pathogenesis of human immunodeficiency virus and targeted by antiretroviral therapy.
Hypersensitivity
Current status of allergy prevalence in Germany: Position paper of the Environmental Medicine Commission of the Robert Koch Institute.
Hypertension
Ceramide mediates vascular dysfunction in diet-induced obesity by PP2A-mediated dephosphorylation of the eNOS-Akt complex.
Hypertension
Comparing nationwide prevalences of hypertension and depression based on claims data and survey data: An example from Germany.
Hypertension
How to compare cardiovascular disease and risk factors in elderly patients with haemophilia with the general population.
Hypertension
[Blood pressure in Germany 2008-2011: results of the German Health Interview and Examination Survey for Adults (DEGS1)].
Infections
Dihydrosphingomyelin impairs HIV-1 infection by rigidifying liquid-ordered membrane domains.
Infertility, Male
The Des-1 protein, required for central spindle assembly and cytokinesis, is associated with mitochondria along the meiotic spindle apparatus and with the contractile ring during male meiosis in Drosophila melanogaster.
Influenza, Human
[Vaccination coverage in German adults: results of the German Health Interview and Examination Survey for Adults (DEGS1)].
Insulin Resistance
Differential regulation of Dihydroceramide desaturase by palmitate vs. monounsaturated fatty acids:Implications to insulin resistance.
Insulin Resistance
Mechanistic interplay between ceramide and insulin resistance.
Leukoencephalopathies
Loss of the sphingolipid desaturase DEGS1 causes hypomyelinating leukodystrophy.
Lung Neoplasms
The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells.
Measles
Vaccine-Preventable Infections in Childcare Workers.
Metabolic Diseases
Ablation of dihydroceramide desaturase 1, a therapeutic target for the treatment of metabolic diseases, simultaneously stimulates anabolic and catabolic signaling.
Mumps
Vaccine-Preventable Infections in Childcare Workers.
Myocardial Infarction
Second vs. first-generation drug-eluting stents in complex lesions subsets: 3 years' follow-up of ERACI IV study.
Myocardial Infarction
[Prevalence of myocardial infarction and coronary heart disease in adults aged 40-79 years in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1)].
Neoplasm Metastasis
Cell cycle-coupled expansion of AR activity promotes cancer progression.
Neoplasm Metastasis
M6A methylation of DEGS2, a key ceramide-synthesizing enzyme, is involved in colorectal cancer progression through ceramide synthesis.
Neoplasm Metastasis
Overexpression of degenerative spermatocyte homolog 1 up-regulates the expression of cyclin D1 and enhances metastatic efficiency in esophageal carcinoma Eca109 cells.
Neoplasms
Alkaline ceramidase 2 (ACER2) and its product dihydrosphingosine mediate the cytotoxicity of N-(4-hydroxyphenyl)retinamide in tumor cells.
Neoplasms
Association of the key genes in the pathophysiology between the Type 2 diabetes and Lung cancer.
Neoplasms
Cationic ceramides and analogues, LCL30 and LCL85, as adjuvants to photodynamic therapy of tumors.
Neoplasms
Dihydroceramide desaturase activity in tumors.
Neoplasms
Gamma-tocotrienol profoundly alters sphingolipids in cancer cells by inhibition of dihydroceramide desaturase and possibly activation of sphingolipid hydrolysis during prolonged treatment.
Neoplasms
M6A methylation of DEGS2, a key ceramide-synthesizing enzyme, is involved in colorectal cancer progression through ceramide synthesis.
Neoplasms
Overexpression of degenerative spermatocyte homolog 1 up-regulates the expression of cyclin D1 and enhances metastatic efficiency in esophageal carcinoma Eca109 cells.
Neoplasms
The anti-cancer drug ABTL0812 induces ER stress-mediated cytotoxic autophagy by increasing dihydroceramide levels in cancer cells.
Neoplasms
[Participation in cancer screening in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1)].
Nervous System Diseases
DEGS1 variant causes neurological disorder.
Nervous System Diseases
DEGS1-associated aberrant sphingolipid metabolism impairs nervous system function in humans.
Neuroblastoma
Cell density dependent reduction of dihydroceramide desaturase activity in neuroblastoma cells.
Neuroblastoma
Involvement of dihydroceramide desaturase in cell cycle progression in human neuroblastoma cells.
Obesity
Increased dihydroceramide/ceramide ratio mediated by defective expression of degs1 impairs adipocyte differentiation and function.
Obesity
Selective Blood Pressure Screening in the Young: Quantification of Population Wide Underestimation of Elevated Blood Pressure.
Obesity
[Overweight and obesity in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1)].
Ovarian Neoplasms
Comprehensive analysis of LASS6 expression and prognostic value in ovarian cancer.
Overweight
[Overweight and obesity in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1)].
Pancreatic Neoplasms
?-Tocotrienol induces apoptosis in pancreatic cancer cells by upregulation of ceramide synthesis and modulation of sphingolipid transport.
Pediatric Obesity
Selective Blood Pressure Screening in the Young: Quantification of Population Wide Underestimation of Elevated Blood Pressure.
Prostatic Neoplasms
Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells.
Prostatic Neoplasms
The Sphingosine Kinase 2 Inhibitor ABC294640 Reduces the Growth of Prostate Cancer Cells and Results in Accumulation of Dihydroceramides In Vitro and In Vivo.
Renal Insufficiency
The Prevalence of Renal Failure.
Rhinitis, Allergic, Seasonal
Current status of allergy prevalence in Germany: Position paper of the Environmental Medicine Commission of the Robert Koch Institute.
Rubella
Vaccine-Preventable Infections in Childcare Workers.
Sarcoma
Dihydroceramide desaturase activity in tumors.
Stroke
Second vs. first-generation drug-eluting stents in complex lesions subsets: 3 years' follow-up of ERACI IV study.
Stroke
[Prevalence of stroke in adults aged 40 to 79 years in Germany: results of the German Health Interview and Examination Survey for Adults (DEGS1)].
Thrombosis
Comparison of the safety between first- and second-generation drug eluting stents Meta-analysis from 19 randomized trials and 16,924 patients.
Vision Disorders
Visual Impairment Is Associated With Depressive Symptoms-Results From the Nationwide German DEGS1 Study.
Whooping Cough
Vaccine-Preventable Infections in Childcare Workers.
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malfunction
DEGS1 ablation induces fat body cell hypertrophy, increased fat body lipid droplet size, and increased abdominal adiposity. In flies, genetic ablation of ifc gene (orthologue for degs1) causes an obese phenotype (larger fat bodies) independent of the caloric intake
malfunction
DEGS1 inhibition enhances insulin sensitivity, DEGS1 ablation induces autophagy and blocks cellular proliferation, and provides protection from chemotherapeutic agents through the activation of prosurvival pathways. Homozygous DEGS1 knockout mouse exhibits a severe phenotype characterised by low survival rate and multiple abnormalities. The heterozygous mice are viable with normal birth Mendelian rates, superficial biochemical phenotypical analysis reveals that mutant degs1 hets mice show higher DhCer/Cer ratios in multiple organs. This is associated with enhanced insulin sensitivity, normal glucose tolerance and resistance to dexamethasone induced insulin resistance. Embryonic fibroblasts from DEGS1knockout mice show enhanced AKT signalling, likely due to the absence of ceramides and not a result of the direct effect of dihydroceramide accumulation. DEGS1 heterozygotes gain more weight over time in comparison to wild-type mice
malfunction
-
DES1 inhibition by specific siRNA causing DES1 activity decrease can ameliorate the increase in ceramide, enhance dihydroceramide elevation, and inhibit the palmitic acid-induced increases in caspase 9 activity and caspase 3 activity, palmitic acid-mediated apoptosis and cell growth inhibition are also attenuated by DES1 downregulation
malfunction
-
Des1 inhibition is primarily responsible for the antiproliferative effects of SKI-II and its analogues. The structure-activity relationship of Des1 inhibition correlates to that required for inhibition of PC-3 cell growth, indicating that Des1 inhibition is a key driver of the anticancer effects of SKI-II and it analogues, which is also supported by lipidomic studies in PC-3 cells
malfunction
DESG1 inhibition block the cell growth, cell migration, cytoskeleton modification, response to insulin, impair of endomembrane trafficking. Fenretinide can exert part of its insulin sensitising effects in liver and muscle by inhibiting DEGS1 and hence decreasing the synthesis of ceramides with the concomitant increase in diydroceramide levels
malfunction
-
dihydroceramide desaturase 1 inhibitors activate autophagy via both dihydroceramide-dependent and independent pathways and the balance between the two pathways influences the final cell fate. Enzyme inhibitors celecoxib, resveratrol, phenoxodiol, and gamma-tocotrienol, but not gamma-tocopherol at 0.05 mM, promote an increase in dihydroceramide, dihydrosphingomyelins, and lactosyldihydroceramides in U-87MG and T-98G cell lines. Similar results are found with the active site-directed Des1 inhibitor XM462
malfunction
gamma-tocotrienol inhibits cellular dihydroceramide desaturase (DEGS) activity without affecting its protein expression or de novo synthesis of sphingolipids. Unlike the effect on dihydroceramides, gamma-tocotrienol decreases ceramides (Cers) after 8-h treatment but increases C18:0-Cer and C16:0-Cer after 16 and 24 h, respectively. The increase of ceramides coincides with gamma-tocotrienol-induced apoptosis and autophagy. Since gamma-tocotrienol inhibits DEGS and decreases de novo ceramide synthesis, elevation of ceramides during prolonged gamma-tocotrienol treatment is likely caused by sphingomeylinase-mediated hydrolysis of sphingomyelin. gamma-Tocotrienol treatment led to a time- and dose-dependent decrease in viability of colon, pancreatic and breast cancer cells, overview
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
malfunction
-
increased DEGS1 activation through myristoylation induces apoptosis mediated by the increase of ceramides
malfunction
-
inhibitors SKi or ABC294640 reduce Des1 activity in Jurkat cells and ABC294640 induces the proteasomal degradation of Des1 in LNCaP-AI prostate cancer cells. Inhibitors SKi, ABC294640, or fenretinide increase the expression of the senescence markers, p53 and p21 in LNCaP-AI prostate cancer cells. The siRNA knockdown of SK1 or SK2 fails to increase p53 and p21 expression, but the former reduces DNA synthesis in LNCaP-AI prostate cancer cells. N-acetylcysteine (reactive oxygen species scavenger) blocks the SK inhibitor-induced increase in p21 and p53 expression but has no effect on the proteasomal degradation of SK1a. In addition, siRNA knockdown of Des1 increases p53 expression while a combination of Des1/SK1 siRNA increases the expression of p21. Modulation of both de novo and sphingolipid rheostat pathways in order to induce growth arrest can be achived by targeting androgen-independent prostate cancer cells with compounds that affect the enzymes Des1 and SK1. N-acetyl cysteine has no effect on the ABC294640-induced proteasomal degradation of Des1, suggesting that the oxidative stress response is down stream of Des1
metabolism
-
DELTA4-desaturation is essential for conversion of the ceramide pool with dihydroxy long-chain sphingoid base and C16/C18 fatty acids into glyosylceramide
metabolism
-
enzymes Des1 and SK1 participate in regulating LNCaP-AI prostate cancer cell growth and this involves p53/p21-dependent and -independent pathways
metabolism
-
in the de novo synthesis, ceramide synthases catalyze the N-acylation of sphinganine to dihydroceramide, which is finally converted to ceramide by introduction of an (E)-4 double bond. The last step is catalyzed by dihydroceramide desaturase 1 (Des1), the enzyme that regulates the balance between dihydroceramide and ceramide
metabolism
-
the enzyme catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides
metabolism
the enzyme catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides
metabolism
the enzyme catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides
metabolism
the enzyme catalyses the final step in the de novo biosynthesis of ceramides controlling the step from dihydroceramides to ceramides
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
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
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
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
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
physiological function
DELTA4-desaturated sphingolipids provide an early signal necessary to trigger the entry into both meiotic and spermatid differentiation pathways during spermatogenesis
physiological function
DELTA4-desaturated sphingolipids provide an early signal necessary to trigger the entry into both meiotic and spermatid differentiation pathways during spermatogenesis
physiological function
DELTA4-desaturated sphingolipids provide an early signal necessary to trigger the entry into both meiotic and spermatid differentiation pathways during spermatogenesis
physiological function
DELTA4-desaturated sphingolipids provide an early signal necessary to trigger the entry into both meiotic and spermatid differentiation pathways during spermatogenesis
physiological function
DELTA4-desaturated sphingolipids provide an early signal necessary to trigger the entry into both meiotic and spermatid differentiation pathways during spermatogenesis
physiological function
the enzyme has no effect on cell viability
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
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
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
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
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
physiological function
-
dihydroceramide desaturase (Des1), the last enzyme in the de novo synthesis of ceramide (Cer), regulates the balance between dihydroceramides (dhCers) and ceramides
physiological function
-
dihydroceramide desaturase 1 (Des1) catalyzes the last step of ceramide synthesis de novo, thus regulating the physiologically relevant balance between dihydrosphingolipids and sphingolipids
physiological function
-
dihydroceramide-desaturase-1-mediated caspase 9 activation through ceramide plays a pivotal role in palmitic acid-induced HepG2 cell apoptosis. Enzyme dihydroceramide desaturase 1 (DES1) plays a key role in palmitic acid-mediated caspase 9 and caspase 3 activation. Palmitoleic acid, an omega-7 monounsaturated fatty acid, reverses palmitic acid-induced apoptosis through DES1 - ceramide - caspase 9 - caspase 3 signaling
physiological function
enzyme dihydroceramide desaturase 1 is the gatekeeper of ceramide induced lipotoxicity. The enzyme is dysregulated by factors such as oxidative stress, hypoxia and inflammation. Dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. DEGS1 is required for the condensation of chromatin (essential in the initiation of the meiosis in the spermatogenesis). Biological role of dihydroceramides, e.g. in apoptosis and autophagy, in the cell cycle, or as regulators of lipid homeostasis, detailed overview
physiological function
enzyme dihydroceramide desaturase 1 is the gatekeeper of ceramide induced lipotoxicity. The enzyme is dysregulated by factors such as oxidative stress, hypoxia and inflammation. Dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. DEGS1 mediates the adaptation to chronic hypoxia and is involved in the induction of insulin resistance mediated by palmitate. Role of fatty acids as modulators of DEGS1 activity and ceramide synthesis. DEGS1 may have a part in fatty acid induced insulin resistance and apoptosis. Biological role of dihydroceramides, e.g. in apoptosis and autophagy, in the cell cycle, or as regulators of lipid homeostasis, detailed overview
physiological function
enzyme dihydroceramide desaturase 1 is the gatekeeper of ceramide induced lipotoxicity. The enzyme is dysregulated by factors such as oxidative stress, hypoxia and inflammation. Dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. DESG1 acts as a vitamin A isomerase in Muller glial cells of the retina. DEGS1 acts as oxygen biosensor. It is involved in the inflammation signalling initiated by interferon gamma and in the inflammation signalling mediated by interleukin-2, IL-2. DEGS1 may play a role in controlling and participating in the levels of ceramides normally associated to inflammation processes. Biological role of dihydroceramides, e.g. in apoptosis and autophagy, in the cell cycle, or as regulators of lipid homeostasis, detailed overview. Dihydroceramides correlate better than ceramides with body mass index (BMI) and waist circumference in cohorts of overweight-obese subjects
physiological function
-
enzyme dihydroceramide desaturase 1 is the gatekeeper of ceramide induced lipotoxicity. The enzyme is dysregulated by factors such as oxidative stress, hypoxia and inflammation. Dihydroceramides constitute a biologically active molecule from the sphingolipid family with certain differential characteristics with respect to its delta-4 unsaturated counterparts, the ceramides. Increased DEGS1 activation through myristoylation induces apoptosis mediated by the increase of ceramides. Biological role of dihydroceramides, e.g. in apoptosis and autophagy, in the cell cycle, or as regulators of lipid homeostasis, detailed overview
physiological function
-
the de novo synthesis of sphingolipids commences with palmitoyl CoA, which is converted into the central lipid ceramide (Cer) in four steps, the last step being the introduction of the double bond at C4 by dihydroceramide desaturase-1 (Des1)
additional information
-
computational ligand docking study and simulations using enzyme structures PDB IDs BC5R and 1IB0, overview
additional information
lipid and ceramide content analysis in untreated and inhibitor-treated ARPE-19 cells, overview
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Beauchamp, E.; Goenaga, D.; Le Bloch, J.; Catheline, D.; Legrand, P.; Rioux, V.
Myristic acid increases the activity of dihydroceramide DELTA4-desaturase 1 through its N-terminal myristoylation
Biochimie
89
1553-1561
2007
Rattus norvegicus (Q5XIF5)
brenda
Beauchamp, E.; Tekpli, X.; Marteil, G.; Lagadic-Gossmann, D.; Legrand, P.; Rioux, V.
N-myristoylation targets dihydroceramide DELTA4-desaturase 1 to mitochondria: Partial involvement in the apoptotic effect of myristic acid
Biochimie
91
1411-1419
2009
Rattus norvegicus (Q564G3)
brenda
Garton, S.; Michaelson, L.V.; Beaudoin, F.; Beale, M.H.; Napier, J.A.
The dihydroceramide desaturase is not essential for cell viability in Schizosaccharomyces pombe
FEBS Lett.
538
192-196
2003
Schizosaccharomyces pombe (O59715), Schizosaccharomyces pombe
brenda
Michel, C.; Van Echten-Deckert, G.; Rother, J.; Sandhoff, K.; Wang, E.; Merrill Jr., A.
Characterization of ceramide synthesis. A dihydroceramide desaturase introduces the 4,5-trans-double bond of sphingosine at the level of dihydroceramide
J. Biol. Chem.
272
22432-22437
1997
Rattus norvegicus (Q564G3)
brenda
Ternes, P.; Franke, S.; Zaehringer, U.; Sperling, P.; Heinz, E.
Identification and characterization of a sphingolipid delta 4-desaturase family
J. Biol. Chem.
277
25512-25518
2002
Caenorhabditis elegans (G5EC63), Mus musculus (O09005), Mus musculus, Homo sapiens (O15121), Homo sapiens, Candida albicans (Q5AJX2), Candida albicans, Drosophila melanogaster (Q94515), Drosophila melanogaster
brenda
Ternes, P.; Wobbe, T.; Schwarz, M.; Albrecht, S.; Feussner, K.; Riezman, I.; Cregg, J.; Heinz, E.; Riezman, H.; Feussner, I.; Warnecke, D.
Two pathways of sphingolipid biosynthesis are separated in the yeast Pichia pastoris
J. Biol. Chem.
286
11401-11414
2011
Komagataella pastoris
brenda
Causeret, C.; Geeraert, L.; Van der Hoeven, G.; Mannaerts, G.; Van Veldhoven, P.
Further characterization of rat dihydroceramide desaturase: Tissue distribution, subcellular localization, and substrate specificity
Lipids
35
1117-1125
2000
Rattus norvegicus (Q564G3)
brenda
Ezanno, H.; Le Bloch, J.; Beauchamp, E.; Lagadic-Gossmann, D.; Legrand, P.; Rioux, V.
Myristic acid increases dihydroceramide DELTA4-desaturase 1 (DES1) activity in cultured rat hepatocytes
Lipids
47
117-128
2012
Rattus norvegicus (Q564G3)
brenda
Beckmann, C.; Rattke, J.; Sperling, P.; Heinz, E.; Boland, W.
Stereochemistry of a bifunctional dihydroceramide DELTA4-desaturase/hydroxylase from Candida albicans; a key enzyme of sphingolipid metabolism
Org. Biomol. Chem.
1
2448-2454
2003
Candida albicans
brenda
Luttgeharm, K.; Kimberlin, A.; Cahoon, R.; Cerny, R.; Napier, J.; Markham, J.; Cahoon, E.
Sphingolipid metabolism is strikingly different between pollen and leaf in Arabidopsis as revealed by compositional and gene expression profiling
Phytochemistry
115
121-129
2015
Arabidopsis thaliana
brenda
Zhu, Q.; Yang, J.; Zhu, R.; Jiang, X.; Li, W.; He, S.; Jin, J.
Dihydroceramide-desaturase-1-mediated caspase 9 activation through ceramide plays a pivotal role in palmitic acid-induced HepG2 cell apoptosis
Apoptosis
21
1033-1044
2016
Homo sapiens
brenda
Rodriguez-Cuenca, S.; Barbarroja, N.; Vidal-Puig, A.
Dihydroceramide desaturase 1, the gatekeeper of ceramide induced lipotoxicity
Biochim. Biophys. Acta
1851
40-50
2015
Chlorocebus aethiops, Mus musculus (O09005), Homo sapiens (O15121), Drosophila melanogaster (Q94515)
brenda
Casasampere, M.; Ordonez, Y.F.; Casas, J.; Fabrias, G.
Dihydroceramide desaturase inhibitors induce autophagy via dihydroceramide-dependent and independent mechanisms
Biochim. Biophys. Acta
1861
264-275
2017
Homo sapiens
brenda
Pou, A.; Abad, J.L.; Ordonez, Y.F.; Garrido, M.; Casas, J.; Fabrias, G.; Delgado, A.
From the configurational preference of dihydroceramide desaturase-1 towards DELTA6-unsaturated substrates to the discovery of a new inhibitor
Chem. Commun. (Camb.)
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2017
Homo sapiens
brenda
Casasampere, M.; Ordonez, Y.F.; Pou, A.; Casas, J.
Inhibitors of dihydroceramide desaturase 1 Therapeutic agents and pharmacological tools to decipher the role of dihydroceramides in cell biology
Chem. Phys. Lipids
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33-44
2016
Drosophila melanogaster, Drosophila melanogaster (Q94515), Mus musculus (O09005), Homo sapiens (O15121), Rattus norvegicus (Q5XIF5)
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Cingolani, F.; Casasampere, M.; Sanllehi, P.; Casas, J.; Bujons, J.; Fabrias, G.
Inhibition of dihydroceramide desaturase activity by the sphingosine kinase inhibitor SKI II
J. Lipid Res.
55
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2014
Homo sapiens
brenda
Aurelio, L.; Scullino, C.V.; Pitman, M.R.; Sexton, A.; Oliver, V.; Davies, L.; Rebello, R.J.; Furic, L.; Creek, D.J.; Pitson, S.M.; Flynn, B.L.
From sphingosine kinase to dihydroceramide desaturase a structure-activity relationship (SAR) study of the enzyme inhibitory and anticancer activity of 4-((4-(4-chlorophenyl)thiazol-2-yl)amino)phenol (SKI-II)
J. Med. Chem.
59
965-984
2016
Homo sapiens
brenda
Jang, Y.; Rao, X.; Jiang, Q.
Gamma-tocotrienol profoundly alters sphingolipids in cancer cells by inhibition of dihydroceramide desaturase and possibly activation of sphingolipid hydrolysis during prolonged treatment
J. Nutr. Biochem.
46
49-56
2017
Homo sapiens (O15121)
brenda
McNaughton, M.; Pitman, M.; Pitson, S.M.; Pyne, N.J.; Pyne, S.
Proteasomal degradation of sphingosine kinase 1 and inhibition of dihydroceramide desaturase by the sphingosine kinase inhibitors, SKi or ABC294640, induces growth arrest in androgen-independent LNCaP-AI prostate cancer cells
Oncotarget
7
16663-16675
2016
Homo sapiens
brenda
Poliakov, E.; Samuel, W.; Duncan, T.; Gutierrez, D.B.; Mata, N.L.; Redmond, T.M.
Inhibitory effects of fenretinide metabolites N-[4-methoxyphenyl]retinamide (MPR) and 4-oxo-N-(4-hydroxyphenyl)retinamide (3-keto-HPR) on fenretinide molecular targets beta-carotene oxygenase 1, stearoyl-CoA desaturase 1 and dihydroceramide DELTA4-desaturase 1
PLoS ONE
12
e0176487
2017
Mus musculus (O09005), Homo sapiens (O15121), Mus musculus C57BL/6 (O09005)
brenda