Please wait a moment until all data is loaded. This message will disappear when all data is loaded.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
3-thiaglutaryl-CoA + acceptor
?
-
-
-
?
4-nitrobutyryl-CoA + acceptor
4-nitro-but-2-enoyl-CoA + reduced acceptor
4-nitrobutyryl-CoA + electron transfer protein
? + CO2 + reduced electron transfer protein
-
-
-
?
5-hexenoyl-CoA + acceptor
? + reduced acceptor
-
-
-
-
?
butyryl-CoA + acceptor
? + reduced acceptor
-
-
-
-
?
glutaconyl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
glutaconyl-CoA + ferrocenium hexafluorophosphate
crotonyl-CoA + CO2 + ferricenium hexafluorophosphate
glutaramyl-CoA + acceptor
? + reduced acceptor
-
-
-
-
?
glutaryl-CoA + 2,6-dichlorophenol indophenol
crotonoyl-CoA + CO2 + reduced 2,6-dichlorophenol indophenol
glutaryl-CoA + acceptor
crotonoyl-CoA + CO2 + reduced acceptor
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
glutaryl-CoA + electron transfer flavoprotein
(E)-but-2-enoyl-CoA + CO2 + reduced electron transfer flavoprotein
glutaryl-CoA + electron transfer flavoprotein
crotonoyl-CoA + CO2 + reduced electron transfer flavoprotein
-
-
-
-
?
glutaryl-CoA + electron transfer protein
crotonoyl-CoA + CO2 + reduced electron transfer protein
-
-
-
?
glutaryl-CoA + electron-transfer flavoprotein
crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein
glutaryl-CoA + FAD
(E)-but-2-enoyl-CoA + CO2 + FADH2
glutaryl-CoA + FAD
crotonoyl-CoA + CO2 + FADH2
glutaryl-CoA + ferricenium hexafluorophosphate
crotonyl-CoA + CO2 + ferrocenium hexafluorophosphate
glutaryl-CoA + human electron-transfer flavoprotein
crotonyl-CoA + CO2 + reduced human electron-transfer flavoprotein
-
-
-
-
r
glutaryl-CoA + phenazine methosulfate
crotonyl-CoA + CO2 + reduced phenazine methosulfate
-
-
-
-
r
glutaryl-CoA + phenylmethylsulfonyl fluoride
?
-
-
-
-
?
glutarylpantetheine + acceptor
crotonylpantetheine + reduced acceptor
hexanoyl-CoA + acceptor
? + reduced acceptor
isovaleryl-CoA + acceptor
? + reduced acceptor
-
-
-
-
?
methyl-glutaryl-CoA + acceptor
methyl-crotonyl-CoA + reduced acceptor
-
-
-
-
?
octanoyl-CoA + acceptor
? + reduced acceptor
pentanoyl-CoA + acceptor
? + reduced acceptor
-
-
-
-
?
proteo-glutaryl-CoA + acceptor
crotonoyl-CoA + CO2 + reduced acceptor
-
-
-
-
?
additional information
?
-
4-nitrobutyryl-CoA + acceptor
4-nitro-but-2-enoyl-CoA + reduced acceptor
-
-
-
?
4-nitrobutyryl-CoA + acceptor
4-nitro-but-2-enoyl-CoA + reduced acceptor
-
-
-
?
glutaconyl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
-
-
r
glutaconyl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
-
-
?
glutaconyl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
involvement of water in catalysis, previously unrecognized and in conflict with a classically held intramolecular 1,3-prototropic shift for protonation of crotonyl-CoA dienolate
-
-
?
glutaconyl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
-
-
-
r
glutaconyl-CoA + ferrocenium hexafluorophosphate
crotonyl-CoA + CO2 + ferricenium hexafluorophosphate
-
-
-
-
?
glutaconyl-CoA + ferrocenium hexafluorophosphate
crotonyl-CoA + CO2 + ferricenium hexafluorophosphate
-
the kinetically favorable product is vinylacetyl-CoA, which is further isomerized to the thermodynamically stable normal product crotonyl-CoA
-
ir
glutaryl-CoA + 2,6-dichlorophenol indophenol
crotonoyl-CoA + CO2 + reduced 2,6-dichlorophenol indophenol
-
-
-
-
?
glutaryl-CoA + 2,6-dichlorophenol indophenol
crotonoyl-CoA + CO2 + reduced 2,6-dichlorophenol indophenol
-
-
-
?
glutaryl-CoA + acceptor
crotonoyl-CoA + CO2 + reduced acceptor
-
-
-
-
?
glutaryl-CoA + acceptor
crotonoyl-CoA + CO2 + reduced acceptor
-
-
-
?
glutaryl-CoA + acceptor
crotonoyl-CoA + CO2 + reduced acceptor
-
part of the degradative pathway of the amino acids tryptophan, lysine, and hydroxylysine, enzyme deficiency leads to glutaric aciduria type I leading to nonspecific developmental delay, hypotonia, and macrocephaly with cerebral atrophyof prenatal onset
-
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptors: electron-transfer flavoprotein, phenylmethylsulfonyl fluoride, 2,6-dichlorophenolindophenol, phenazine methosulfate, methylene blue
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
-
-
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
-
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
site directed mutagenesis of binding site and analysis of mechanism
-
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptors: electron-transfer flavoprotein, phenylmethylsulfonyl fluoride, 2,6-dichlorophenolindophenol, phenazine methosulfate, methylene blue
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptors: electron-transfer flavoprotein, phenylmethylsulfonyl fluoride, 2,6-dichlorophenolindophenol, phenazine methosulfate, methylene blue
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
analysis of mechanism , redox potential
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
analysis of decarboxylation reaction, enzyme has intrinsic enoyl-CoA hydratase activity
-
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptor: ferrocenium hexafluorophosphate
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptor: ferrocenium hexafluorophosphate
-
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
involved in mitochondrial degradation of lysine, hydroxylysine, tryptophan
-
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
analysis of mutations causing glutaric acidemia type I
-
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
deficiency causes glutaric aciduria type I, study on activities in wild type and mutants
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
inhibition of redox half-reaction in mitochondria leads to oxidation of glutaryl-CoA to glutaconyl-CoA in peroxisomes and its decarboxylation by glutaryl-decarboxylase in mitochondria
-
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptors: electron-transfer flavoprotein, phenylmethylsulfonyl fluoride, 2,6-dichlorophenolindophenol, phenazine methosulfate, methylene blue
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptors: electron-transfer flavoprotein, phenylmethylsulfonyl fluoride, 2,6-dichlorophenolindophenol, phenazine methosulfate, methylene blue
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptors: electron-transfer flavoprotein, phenylmethylsulfonyl fluoride, 2,6-dichlorophenolindophenol, phenazine methosulfate, methylene blue
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptors: electron-transfer flavoprotein, phenylmethylsulfonyl fluoride, 2,6-dichlorophenolindophenol, phenazine methosulfate, methylene blue
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptors: electron-transfer flavoprotein, phenylmethylsulfonyl fluoride, 2,6-dichlorophenolindophenol, phenazine methosulfate, methylene blue
-
?
glutaryl-CoA + acceptor
crotonyl-CoA + CO2 + reduced acceptor
-
acceptors: electron-transfer flavoprotein, phenylmethylsulfonyl fluoride, 2,6-dichlorophenolindophenol, phenazine methosulfate, methylene blue
-
?
glutaryl-CoA + electron transfer flavoprotein
(E)-but-2-enoyl-CoA + CO2 + reduced electron transfer flavoprotein
-
-
-
?
glutaryl-CoA + electron transfer flavoprotein
(E)-but-2-enoyl-CoA + CO2 + reduced electron transfer flavoprotein
-
-
-
?
glutaryl-CoA + electron transfer flavoprotein
(E)-but-2-enoyl-CoA + CO2 + reduced electron transfer flavoprotein
-
-
-
-
?
glutaryl-CoA + electron-transfer flavoprotein
crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein
-
-
-
-
r
glutaryl-CoA + electron-transfer flavoprotein
crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein
overall reaction
-
-
?
glutaryl-CoA + electron-transfer flavoprotein
crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein
-
-
-
-
r
glutaryl-CoA + electron-transfer flavoprotein
crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein
-
-
-
-
r
glutaryl-CoA + electron-transfer flavoprotein
crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein
-
-
-
-
r
glutaryl-CoA + FAD
(E)-but-2-enoyl-CoA + CO2 + FADH2
-
-
-
-
?
glutaryl-CoA + FAD
(E)-but-2-enoyl-CoA + CO2 + FADH2
-
GCD catalyzes the oxidative decarboxylation of the gamma-carboxylate of the substrate, glutaryl-CoA, to yield crotonyl-CoA and CO2.
-
-
?
glutaryl-CoA + FAD
(E)-but-2-enoyl-CoA + CO2 + FADH2
-
-
-
-
?
glutaryl-CoA + FAD
crotonoyl-CoA + CO2 + FADH2
-
via intermediate glutaconyl-CoA
-
-
?
glutaryl-CoA + FAD
crotonoyl-CoA + CO2 + FADH2
-
via intermediate glutaconyl-CoA, detection using ferrocenium hexafluorophosphate
-
-
?
glutaryl-CoA + FAD
crotonoyl-CoA + CO2 + FADH2
-
-
-
-
?
glutaryl-CoA + FAD
crotonoyl-CoA + CO2 + FADH2
-
-
-
?
glutaryl-CoA + FAD
crotonoyl-CoA + CO2 + FADH2
detection using ferrocenium hexafluorophosphate
-
-
?
glutaryl-CoA + ferricenium hexafluorophosphate
crotonyl-CoA + CO2 + ferrocenium hexafluorophosphate
-
-
-
?
glutaryl-CoA + ferricenium hexafluorophosphate
crotonyl-CoA + CO2 + ferrocenium hexafluorophosphate
-
-
-
-
?
glutaryl-CoA + ferricenium hexafluorophosphate
crotonyl-CoA + CO2 + ferrocenium hexafluorophosphate
-
-
-
-
?
glutarylpantetheine + acceptor
crotonylpantetheine + reduced acceptor
-
-
-
?
glutarylpantetheine + acceptor
crotonylpantetheine + reduced acceptor
-
-
-
?
hexanoyl-CoA + acceptor
? + reduced acceptor
-
-
-
-
?
hexanoyl-CoA + acceptor
? + reduced acceptor
-
-
-
-
?
octanoyl-CoA + acceptor
? + reduced acceptor
-
-
-
-
?
octanoyl-CoA + acceptor
? + reduced acceptor
-
-
-
-
?
additional information
?
-
-
enzyme deficiency leads to glutaric aciduria type I with accumulation of glutarate and 3-hydroxyglutarate with subsequent neuronal destruction during metabolic crises triggered by catabolic stress, treatment with isocaloric glucose and carnitine infusion and suspension of protein intake can recover the patient from apathy
-
-
?
additional information
?
-
-
GCDH is a central enzyme in the catabolic pathway of L-tryptophan, L-lysine, and L-hydroxylysine
-
-
?
additional information
?
-
the decarboxylating and nondecarboxylating, EC 1.3.99.X from Desulfococcus multivorans, capabilities are provided by complex structural changes around the glutaconyl carboxylate group, the key factor being a Tyr to Val exchange strictly conserved between the two GDH types
-
-
?
additional information
?
-
GCDH enzyme activity is measured following the reduction of DCPIP at 600 nm, with either PMS (artificial electron acceptor) or recombinant human ETF (GCDH natural electron acceptor), and glutaryl-CoA as electron donor, in 10 mM HEPES, pH 7.8
-
-
-
additional information
?
-
-
GCDH enzyme activity is measured following the reduction of DCPIP at 600 nm, with either PMS (artificial electron acceptor) or recombinant human ETF (GCDH natural electron acceptor), and glutaryl-CoA as electron donor, in 10 mM HEPES, pH 7.8
-
-
-
additional information
?
-
-
spectral and electrochemical properties
-
-
?
additional information
?
-
-
study on mechanism
-
-
?
additional information
?
-
-
the enzyme is also active with butyryl-CoA, hexanoyl-CoA, octanoyl-CoA, and decanoyl-CoA, but is inactive with decanoyl-CoA and dodecanoyl-CoA, substrate specificity, overview
-
-
?
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
evolution
-
glutaryl-CoA dehydrogenase belongs to the acyl-CoA dehydrogenase enzyme family
evolution
glutaryl-CoA dehydrogenase belongs to the acyl-CoA dehydrogenase enzyme family, phylogenetic tree, overview
evolution
-
the enzyme is a member of the acyl-CoA dehydrogenase (ACD) family of flavoproteins
evolution
-
glutaryl-CoA dehydrogenase belongs to the acyl-CoA dehydrogenase enzyme family, phylogenetic tree, overview
-
malfunction
injection of (3H)-labeled 3-hydroxyglutaric acid into 6 week-old Gcdh knockout mice, a model of glutaric aciduria type 1, reveal a low recovery in kidney, liver, or brain tissue that does not differ from control mice. Significant amounts of 3-hydroxyglutaric acid are found to be excreted via the intestinal tract. Exposure of knockout mice to a high protein diet leads to an encephalopathic crisis, vacuolization in the brain, and death after 4-5 days. Under these conditions, high amounts of injected 3H-3-hydroxyglutaric acid are found in kidneys of Gcdh knockout mice, whereas the radioactivity recovered in brain and blood is reduced. The data demonstrate that under conditions mimicking encephalopathic crises the blood-brain barrier appears to remain intact
malfunction
-
defects in glutaryl-CoA dehydrogenase are involved in glutaric acidemia type 1, an inherited metabolic disorder which can cause macrocephaly, muscular rigidity, spastic paralysis and other progressive movement disorders in humans
malfunction
-
in glutaric aciduria type 1, glutaryl-CoA dehydrogenase deficiency is responsible for the accumulation of glutaric acid and striatal degeneration, GA1-induced striatal degeneration is partially caspase-dependent, mechanism, overview
malfunction
glutaric aciduria type I (GA-I) is an autosomal recessive neurometabolic disease caused by mutations in the GCDH gene that encodes for glutaryl-CoA dehydrogenase (GCDH), a flavoprotein involved in the metabolism of tryptophan, lysine and hydroxylysin
malfunction
-
in glutaric aciduria type 1, glutaryl-CoA dehydrogenase deficiency is responsible for the accumulation of glutaric acid and striatal degeneration, GA1-induced striatal degeneration is partially caspase-dependent, mechanism, overview
-
metabolism
glutaryl-coenzyme A dehydrogenases involved in amino acid degradation catalyze both the dehydrogenation and decarboxylation of glutaryl-CoA to crotonoyl-CoA and CO2
metabolism
-
the enzyme catalyzes an intermediate step in the metabolic breakdown of lysine and tryptophan
metabolism
the enzyme catalyzes an intermediate step in the metabolic breakdown of lysine and tryptophan
metabolism
glutaryl-CoA dehydrogenase (GCDH), a flavoprotein, is involved in the metabolism of tryptophan, lysine and hydroxylysin
metabolism
-
the enzyme catalyzes an intermediate step in the metabolic breakdown of lysine and tryptophan
-
physiological function
-
glutaryl-CoA dehydrogenase activity is required for the catabolism of the essential ketogenic amino acids lysine and tryptophan
physiological function
GCDH interacts directly, among others, with mitochondrial proteins, dihydrolipoamide S-succinyltransferase involved in the formation of glutaryl-CoA, and the beta-subunit of the electron transfer flavoprotein serving as electron acceptordihydrolipoamide S-succinyltransferase involved in the formation of glutaryl-CoA, and the beta-subunit of the electron transfer flavoprotein serving as electron acceptor
additional information
-
glutaric aciduria type 1, GA 1, cause by glutaryl-CoA dehydrogenase deficiency, is an inherited disorder of lysine and tryptophan catabolism that typically manifests in infants with acute cerebral injury associated with intercurrent illness, phenotypoes in black South African population, overview
additional information
-
Glutaryl-CoA dehydrogenase deficiency causes glutaric aciduria type 1, GA1, an autosomal recessive disorder of mitochondrial lysine and tryptophan degradation. In glutaric aciduria type 1, glutaryl-CoA and its derivatives are produced from intracerebral lysine and entrapped at high concentrations within the brain, where they interfere with energy metabolism. Biochemical toxicity triggers stroke-like striatal degeneration in susceptible children under 2 years of age. Although metabolic toxicity appears central to the pathophysiology of striatal necrosis, cerebrovascular changes probably also contribute to the process. Cerebral haemodynamics and the glutaric aciduria type 1 toxidrome, phenotype with atrophic striatal lesions, increased cerebrospinal fluid volume, interstitial brain oedema, acute striatal degeneration, low regional cerebral blood volume and signs of ischaemia, detailed overview in Amish population patients
additional information
the apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the cofactor-binding pocket relative to the ternary complex of the highly homologous human GCDH
additional information
-
the apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the cofactor-binding pocket relative to the ternary complex of the highly homologous human GCDH
additional information
structure comparisons of wild-type and mutant enzyme proteins, FAD binding structures, overview
additional information
-
structure comparisons of wild-type and mutant enzyme proteins, FAD binding structures, overview
additional information
-
the apo structure of GCDH from Burkholderia pseudomallei reveals a loss of secondary structure and increased disorder in the cofactor-binding pocket relative to the ternary complex of the highly homologous human GCDH
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
A293T
-
naturally occruing mutation in GCDH
A377T
naturally occurring mutation from patient with glutaric acidemia type I, dissociation to inactive monomers or dimers
A377V
naturally occurring mutation from patient with glutaric acidemia type I, dissociation to inactive monomers or dimers
A389E
naturally occurring mutation from patient with glutaric acidemia type I, dissociation to inactive monomers or dimers
A389V
naturally occurring mutation from patient with glutaric acidemia type I, dissociation to inactive monomers or dimers
A421T
-
site-directed mutagenesis, altered Km, kcat is only slightly affected, slightly reduced activity compared to the wild-type enzyme
A421V
-
site-directed mutagenesis, altered Km, kcat is only slightly affected, reduced activity compared to the wild-type enzyme
A433E
-
site-directed mutagenesis, nearly inactive mutant
A433V
-
site-directed mutagenesis, altered Km, kcat is only slightly affected, reduced activity compared to the wild-type enzyme
C1296T
-
the mutation leads to glutaryl-CoA dehydrogenase deficiency
F236L/S259P
-
this genotype exhibits 3% GCDH activity
G171W/V410M
-
this genotype exhibits 8% GCDH activity
M1V/R227P
-
this genotype exhibits 4% GCDH activity
M263V
-
analysis of a naturally occurring mutation in a Turkish patient with glutaric aciduria type I
Q59P
-
naturally occruing mutation in GCDH
R161Q/C228R
-
this genotype exhibits 25% GCDH activity
R402W
-
naturally occruing mutation in GCDH
R88A
expression of mutant results in the disruption of mitochondrial architecture forming longitudinal structures composed of stacks of cristae and partial loss of the outer mitochondrial membrane
R88C
expression of mutant results in the disruption of mitochondrial architecture forming longitudinal structures composed of stacks of cristae and partial loss of the outer mitochondrial membrane
R88K
expression of mutant results in the disruption of mitochondrial architecture forming longitudinal structures composed of stacks of cristae and partial loss of the outer mitochondrial membrane
R88M
expression of mutant results in the disruption of mitochondrial architecture forming longitudinal structures composed of stacks of cristae and partial loss of the outer mitochondrial membrane
S225W
-
this genotype exhibits 6% GCDH activity
T385M
naturally occurring mutation from patient with glutaric acidemia type I, dissociation to inactive monomers or dimers
T429M
-
site-directed mutagenesis, altered Km, kcat is only slightly affected, reduced activity compared to the wild-type enzyme
V400M
a naturally occuring GCDH disease-related mutation involved in glutaric aciduria type I (GA-I). Heterozygous patients harbouring the two mutations GCDH-p.Arg227Pro and GCDH-p.Val400Met show increased residual enzymatic activity in relation to homozygous patients with only one of the mutations, suggesting a complementation effect between the two. Thermal stress affects cofactor binding in the GCDH-p.Val400Met mutant. In vivo the p.Val400Met variant displays impaired interaction with the partner ETF, resulting in the lower values observed in patient fibroblasts. The mutant shows 24% reduced activity compared to wild-type
Y155H
mutant exhibits a reduced interaction with dihydrolipoamide succinyl transferase
Y155H/A421V
-
this genotype exhibits 5% GCDH activity
E370A
-
site-directed mutagenesis, inactive mutant
E370Q
-
site-directed mutagenesis, the mutant shows highy reduced activity compared to the wild-type enzyme
E370D
mutant is more sensitive against inactivation by 3-thiaglutaryl-CoA compared to the wild-type enzyme, irreversible inactivation
E370D
the mutation results in a 24% decrease in the rate constant for proton abstraction at C-2 of 3-thiaglutaryl-CoA, the net rate constant for flavin reduction due to hydride transfer from C-3 of the natural substrate decreases by 81% due to the mutation
E370Q
-
does not catalyze detectable exchange of 4c methyl protons of crotonyl-CoA
E370Q
the dienolate intermediate observed upon decarboxylation of glutaconyl-CoA can be detected with E370Q GCD but not with wild-type, because the crotonyl-CoA dienolate forms a charge-transfer complex with the oxidized FAD and the substitution of a glutamine residue for Glu370 prevents rapid protonation of the dienolate
R227P
-
naturally occurring mutation leading to reduced enzyme activity, mildly altered phenotype, physiological analysis, absence of glutarate and 3-hydroxyglutarate in serum and in urine, overview
R227P
a naturally occuring GCDH disease-related mutation involved in glutaric aciduria type I (GA-I). Heterozygous patients harbouring the two mutations GCDH-p.Arg227Pro and GCDH-p.Val400Met show increased residual enzymatic activity in relation to homozygous patients with only one of the mutations, suggesting a complementation effect between the two. The mutant shows 95% reduced activity compared to wild-type
additional information
the CIBdgcdR mutant strain is unable to grow in pimelate, glutarate or benzoate as sole carbon sources
additional information
studies of 18 missense mutations identified in glutaric aciduria type 1 patients affecting surface amino acids. The stability of half of the GCDH mutants is significantly reduced. None of the mutations impairs the 3D structure of GCDH. All GCDH mutants are correctly translocated into mitochondria
additional information
-
studies of 18 missense mutations identified in glutaric aciduria type 1 patients affecting surface amino acids. The stability of half of the GCDH mutants is significantly reduced. None of the mutations impairs the 3D structure of GCDH. All GCDH mutants are correctly translocated into mitochondria
additional information
-
constructionof a lentiviral vector containing short hairpin RNA targeted against the GCDH gene expression (lentivirus-shRNA) in neurons
additional information
-
constructionof a lentiviral vector containing short hairpin RNA targeted against the GCDH gene expression (lentivirus-shRNA) in neurons
-
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Please wait a moment until the data is sorted. This message will disappear when the data is sorted.
Gomes, B.; Fendrich, G.; Abeles, R.H.
Mechanism of action of glutaryl-CoA and butyryl-CoA dehydrogenases. Purification of glutaryl-CoA dehydrogenase
Biochemistry
20
1481-1490
1981
Pseudomonas fluorescens
brenda
Byron, C.M.; Stankovich, M.T.; Husain, M.
Spectral and electrochemical properties of glutaryl-CoA dehydrogenase from Paracoccus denitrificans
Biochemistry
29
3691-3700
1990
Paracoccus denitrificans
brenda
McMillan, T.A.; Gibson, K.M.; Sweetman, L.; Meyers, G.S.; Green, R.
Conservation of central nervous system glutaryl-coenzyme A dehydrogenase in fruit-eating bats with glutaric aciduria and deficient hepatic glutaryl-coenzyme A dehydrogenase
J. Biol. Chem.
263
17258-17261
1988
Rousettus aegyptiacus
brenda
Lenich, A.C.; Goodman, S.I.
The purification and characterization of glutaryl-coenzyme A dehydrogenase from porcine and human liver
J. Biol. Chem.
261
4090-4096
1986
Homo sapiens, Sus scrofa
brenda
Husain, M.; Steenkamp, D.J.
Partial purification and characterization of glutaryl-coenzyme A dehydrogenase, electron transfer flavoprotein, and electron transfer flavoprotein-Q oxidoreductase from Paracoccus denitrificans
J. Bacteriol.
163
709-715
1985
Paracoccus denitrificans
brenda
Vamecq, J.; van Hoof, F.
Implication of a peroxisomal enzyme in the catabolism of glutaryl-CoA
Biochem. J.
221
203-211
1984
Mus musculus
brenda
Besrat, A.; Polan, C.E.; Henderson, L.M.
Mammalian metabolism of glutaric acid
J. Biol. Chem.
244
1461-1467
1969
Bos taurus
brenda
Liesert, M.; Zschocke, J.; Hoffmann, G.F.; Muhlhauser, N.; Buckel, W.
Biochemistry of glutaric aciduria type I: activities of in vitro expressed wild-type and mutant cDNA encoding human glutaryl-CoA dehydrogenase
J. Inherit. Metab. Dis.
22
256-258
1999
Homo sapiens
brenda
Goodman, S.I.; Kratz, L.E.; DiGiulio, K.A.; Biery, B.J.; Goodman, K.E.; Isaya, G.; Frerman, F.E.
Cloning of glutaryl-CoA dehydrogenase cDNA, and expression of wild type and mutant enzymes in Escherichia coli
Hum. Mol. Genet.
4
1493-1498
1995
Homo sapiens
brenda
Goodman, S.I.; Stein, D.E.; Schlesinger, S.; Christensen, E.; Schwartz, M.; Greenberg, C.R.; Elpeleg, O.N.
Glutaryl-CoA dehydrogenase mutations in glutaric acidemia (type I): Review and report of thirty novel mutations
Hum. Mutat.
12
141-144
1998
Homo sapiens
brenda
Haertel, U.; Eckel, E.; Koch, J.; Fuchs, G.; Linder, D.; Buckel, W.
Purification of glutaryl-CoA dehydrogenase from Pseudomonas sp., an enzyme involved in the anaerobic degradation of benzoate
Arch. Microbiol.
159
174-181
1993
Pseudomonas sp.
brenda
Dwyer, T.M.; Rao, K.S.; Goodman, S.I.; Frerman, F.E.
Proton abstraction reaction, steady-state kinetics, and oxidation-reduction potential of human glutaryl-CoA dehydrogenase
Biochemistry
39
11488-11499
2000
Homo sapiens
brenda
Westover, J.B.; Goodman, S.I.; Frerman, F.E.
Binding, hydration, and decarboxylation of the reaction intermediate glutaconyl-Coenzyme A by human Glutaryl-CoA dehydrogenase
Biochemistry
40
14106-14114
2001
Homo sapiens
brenda
Rao, K.S.; Vander Velde, D.; Dwyer, T.M.; Goodman, S.I.; Frerman, F.E.
Alternate substrates of human glutaryl-CoA dehydrogenase: Structure and reactivity of substrates, and identification of a novel 2-enoyl-CoA product
Biochemistry
41
1274-1284
2002
Homo sapiens
brenda
Dwyer, T.M.; Rao, K.S.; Westover, J.B.; Kim, J.J.P.; Frerman, F.E.
The function of Arg-94 in the oxidation and decarboxylation of glutaryl-CoA by human glutaryl-CoA dehydrogenase
J. Biol. Chem.
276
133-138
2001
Homo sapiens
brenda
Woontner, M.; Crnic, L.S.; Koeller, D.M.
Analysis of the expression of murine glutaryl-CoA dehydrogenase: in vitro and in vivo studies
Mol. Genet. Metab.
69
116-122
2000
Mus musculus
brenda
Vamecq, J.; de Hoffmann, E.; van Hoff, F.
Mitochondrial and peroxisomal metabolism of glutaryl-CoA
Eur. J. Biochem.
146
663-669
1985
Mus musculus
brenda
Fu, Z.; Wang, M.; Paschke, R.; Rao, K.S.; Frerman, F.E.; Kim, J.J.
Crystal structures of human glutaryl-CoA dehydrogenase with and without an alternate substrate: structural bases of dehydrogenation and decarboxylation reactions
Biochemistry
43
9674-9684
2004
Homo sapiens (Q92947), Homo sapiens
brenda
Rao, K.S.; Albro, M.; Vockley, J.; Frerman, F.E.
Mechanism-based inactivation of human glutaryl-CoA dehydrogenase by 2-pentynoyl-CoA: rationale for enhanced reactivity
J. Biol. Chem.
278
26342-26350
2003
Homo sapiens (Q92947), Homo sapiens
brenda
Muehlhausen, C.; Christensen, E.; Schwartz, M.; Muschol, N.; Ullrich, K.; Lukacs, Z.
Severe phenotype despite high residual glutaryl-CoA dehydrogenase activity: a novel mutation in a Turkish patient with glutaric aciduria type I
J. Inherit. Metab. Dis.
26
713-714
2003
Homo sapiens
brenda
Treacy, E.P.; Lee-Chong, A.; Roche, G.; Lynch, B.; Ryan, S.; Goodman, S.
Profound neurological presentation resulting from homozygosity for a mild glutaryl-CoA dehydrogenase mutation with a minimal biochemical phenotype
J. Inherit. Metab. Dis.
26
72-74
2003
Homo sapiens
brenda
Westover, J.B.; Goodman, S.I.; Frerman, F.E.
Pathogenic mutations in the carboxyl-terminal domain of glutaryl-CoA dehydrogenase: effects on catalytic activity and the stability of the tetramer
Mol. Genet. Metab.
79
245-256
2003
Homo sapiens
brenda
Rao, K.S.; Albro, M.; Zirrolli, J.A.; Vander Velde, D.; Jones, D.N.M.; Frerman, F.E.
Protonation of crotonyl-CoA dienolate by human glutaryl-CoA dehydrogenase occurs by solvent-derived protons
Biochemistry
44
13932-13940
2005
Homo sapiens
brenda
Rao, K.S.; Albro, M.; Dwyer, T.M.; Frerman, F.E.
Kinetic mechanism of glutaryl-CoA dehydrogenase
Biochemistry
45
15853-15861
2006
Homo sapiens (Q92947)
brenda
Yeh, C.S.; Wang, J.Y.; Cheng, T.L.; Juan, C.H.; Wu, C.H.; Lin, S.R.
Fatty acid metabolism pathway play an important role in carcinogenesis of human colorectal cancers by Microarray-Bioinformatics analysis
Cancer Lett.
233
297-308
2006
Homo sapiens
brenda
Rao, K.S.; Fu, Z.; Albro, M.; Narayanan, B.; Baddam, S.; Lee, H.J.; Kim, J.J.; Frerman, F.E.
The effect of a Glu370Asp mutation in glutaryl-CoA dehydrogenase on proton transfer to the dienolate intermediate
Biochemistry
46
14468-14477
2007
Homo sapiens (Q92947)
brenda
Strauss, K.A.; Lazovic, J.; Wintermark, M.; Morton, D.H.
Multimodal imaging of striatal degeneration in Amish patients with glutaryl-CoA dehydrogenase deficiency
Brain
130
1905-1920
2007
Homo sapiens
brenda
Blazquez, B.; Carmona, M.; Garcia, J.L.; Diaz, E.
Identification and analysis of a glutaryl-CoA dehydrogenase-encoding gene and its cognate transcriptional regulator from Azoarcus sp. CIB
Environ. Microbiol.
10
474-482
2008
Pseudomonas putida, Azoarcus sp. (B0EVL5), Pseudomonas putida KT 2240
brenda
Koelker, S.; Christensen, E.; Leonard, J.V.; Greenberg, C.R.; Burlina, A.B.; Burlina, A.P.; Dixon, M.; Duran, M.; Goodman, S.I.; Koeller, D.M.; Mueller, E.; Naughten, E.R.; Neumaier-Probst, E.; Okun, J.G.; Kyllerman, M.; Surtees, R.A.; Wilcken, B.; Hoffmann, G.F.; Burgard, P.
Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I)
J. Inherit. Metab. Dis.
30
5-22
2007
Homo sapiens
brenda
Sauer, S.W.
Biochemistry and bioenergetics of glutaryl-CoA dehydrogenase deficiency
J. Inherit. Metab. Dis.
30
673-680
2007
Homo sapiens
brenda
Lopez-Laso, E.; Garcia-Villoria, J.; Martin, E.; Duque, P.; Cano, A.; Ribes, A.
Classic and late-onset neurological disease in two siblings with glutaryl-CoA dehydrogenase deficiency
J. Inherit. Metab. Dis.
30
979
2007
Homo sapiens
brenda
McClelland Verity , M.V.; Gissen Pau, G.P.; Hendriksz Chri, H.C.; Chakrapani Anupa, C.A.
Glutaryl-CoA dehydrogenase deficiency
Pediatr. Res.
61
134-135
2007
Homo sapiens
-
brenda
Koelker, S.; Garbade, S.F.; Boy, N.; Maier, E.M.; Meissner, T.; Muehlhausen, C.; Hennermann, J.B.; Luecke, T.; Haeberle, J.; Baumkoetter, J.; Haller, W.; Muller, E.; Zschocke, J.; Burgard, P.; Hoffmann, G.F.
Decline of acute encephalopathic crises in children with glutaryl-CoA dehydrogenase deficiency identified by newborn screening in Germany
Pediatr. Res.
62
357-363
2007
Homo sapiens
brenda
Keyser, B.; Glatzel, M.; Stellmer, F.; Kortmann, B.; Lukacs, Z.; Koelker, S.; Sauer, S.W.; Muschol, N.; Herdering, W.; Thiem, J.; Goodman, S.I.; Koeller, D.M.; Ullrich, K.; Braulke, T.; Muehlhausen, C.
Transport and distribution of 3-hydroxyglutaric acid before and during induced encephalopathic crises in a mouse model of glutaric aciduria type 1
Biochim. Biophys. Acta
1782
385-390
2008
Mus musculus (Q60759), Mus musculus
brenda
Wischgoll, S.; Demmer, U.; Warkentin, E.; Guenther, R.; Boll, M.; Ermler, U.
Structural basis for promoting and preventing decarboxylation in glutaryl-coenzyme A dehydrogenases
Biochemistry
49
5350-5357
2010
Homo sapiens (Q92947)
brenda
Strauss, K.A.; Donnelly, P.; Wintermark, M.
Cerebral haemodynamics in patients with glutaryl-coenzyme A dehydrogenase deficiency
Brain
133
76-92
2010
Homo sapiens
brenda
Wischgoll, S.; Taubert, M.; Peters, F.; Jehmlich, N.; von Bergen, M.; Boll, M.
Decarboxylating and nondecarboxylating glutaryl-coenzyme A dehydrogenases in the aromatic metabolism of obligately anaerobic bacteria
J. Bacteriol.
191
4401-4409
2009
Geobacter metallireducens
brenda
van der Watt, G.; Owen, E.P.; Berman, P.; Meldau, S.; Watermeyer, N.; Olpin, S.E.; Manning, N.J.; Baumgarten, I.; Leisegang, F.; Henderson, H.
Glutaric aciduria type 1 in South Africa-high incidence of glutaryl-CoA dehydrogenase deficiency in black South Africans
Mol. Genet. Metab.
101
178-182
2010
Homo sapiens
brenda
Begley, D.W.; Davies, D.R.; Hartley, R.C.; Hewitt, S.N.; Rychel, A.L.; Myler, P.J.; Van Voorhis, W.C.; Staker, B.L.; Stewart, L.J.
Probing conformational states of glutaryl-CoA dehydrogenase by fragment screening
Acta Crystallogr. Sect. F
67
1060-1069
2011
Homo sapiens, Burkholderia pseudomallei (Q3JP94), Burkholderia pseudomallei, Burkholderia pseudomallei 1710b (Q3JP94)
brenda
Wu, L.; Qiao, Y.; Gao, J.; Deng, G.; Yu, W.; Chen, G.; Li, D.
Functional characterization of rat glutaryl-CoA dehydrogenase and its comparison with straight-chain acyl-CoA dehydrogenase
Bioorg. Med. Chem. Lett.
21
6667-6673
2011
Rattus norvegicus
brenda
Gao, J.; Zhang, C.; Fu, X.; Yi, Q.; Tian, F.; Ning, Q.; Luo, X.
Effects of targeted suppression of glutaryl-CoA dehydrogenase by lentivirus-mediated shRNA and excessive intake of lysine on apoptosis in rat striatal neurons
PLoS ONE
8
e63084
2013
Rattus norvegicus, Rattus norvegicus Sprague-Dawley
brenda
Schmiesing, J.; Lohmoeller, B.; Schweizer, M.; Tidow, H.; Gersting, S.W.; Muntau, A.C.; Braulke, T.; Muehlhausen, C.
Disease-causing mutations affecting surface residues of mitochondrial glutaryl-CoA dehydrogenase impair stability, heteromeric complex formation and mitochondria architecture
Hum. Mol. Genet.
26
538-551
2017
Homo sapiens (Q92947), Homo sapiens
brenda
Braissant, O.; Jafari, P.; Remacle, N.; Cudre-Cung, H.P.; Do Vale Pereira, S.; Ballhausen, D.
Immunolocalization of glutaryl-CoA dehydrogenase (GCDH) in adult and embryonic rat brain and peripheral tissues
Neuroscience
343
355-363
2017
Rattus norvegicus
brenda
Schmiesing, J.; Schlueter, H.; Ullrich, K.; Braulke, T.; Muehlhausen, C.
Interaction of glutaric aciduria type 1-related glutaryl-CoA dehydrogenase with mitochondrial matrix proteins
PLoS ONE
9
e87715
2014
Homo sapiens (Q92947), Homo sapiens
brenda
Ribeiro, J.; Lucas, T.; Bross, P.; Gomes, C.; Henriques, B.
Potential complementation effects of two disease-associated mutations in tetrameric glutaryl-CoA dehydrogenase is due to inter subunit stability-activity counterbalance
Biochim. Biophys. Acta
1868
140269
2020
Homo sapiens (Q92947), Homo sapiens
brenda