Any feedback?
Literature summary extracted from
- Potential complementation effects of two disease-associated mutations in tetrameric glutaryl-CoA dehydrogenase is due to inter subunit stability-activity counterbalance (2020), Biochim. Biophys. Acta, 1868, 140269 .
Cloned(Commentary)
| EC Number | Cloned (Comment) | Organism |
|---|---|---|
| 1.3.8.6 | recombinant expression of C-terminally His6-tagged wild-type and mutant enzymes in Escherichia coli strain BL21(DE3) | Homo sapiens |
Protein Variants
| EC Number | Protein Variants | Comment | Organism |
|---|---|---|---|
| 1.3.8.6 | 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 | Homo sapiens |
| 1.3.8.6 | 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 | Homo sapiens |
KM Value [mM]
| EC Number | KM Value [mM] | KM Value Maximum [mM] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.3.8.6 | additional information | - |
additional information | Michaelis-Menten steady-state kinetic analysis for wild-type and mutant enzymes | Homo sapiens | |
| 1.3.8.6 | 0.02 | - |
glutaryl-CoA | recombinant mutant V400M with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens |  |
| 1.3.8.6 | 0.0211 | - |
glutaryl-CoA | recombinant wild-type enzyme with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 1.3.8.6 | 0.0326 | - |
glutaryl-CoA | recombinant mutant R227P with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
Localization
| EC Number | Localization | Comment | Organism | GeneOntology No. | Textmining |
|---|---|---|---|---|---|
| 1.3.8.6 | mitochondrion | - |
Homo sapiens | 5739 | - |
Natural Substrates/ Products (Substrates)
| EC Number | Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.3.8.6 | glutaryl-CoA + electron-transfer flavoprotein | Homo sapiens | overall reaction | crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein | - |
? | |
Organism
| EC Number | Organism | UniProt | Comment | Textmining |
|---|---|---|---|---|
| 1.3.8.6 | Homo sapiens | Q92947 | - |
- |
Purification (Commentary)
| EC Number | Purification (Comment) | Organism |
|---|---|---|
| 1.3.8.6 | recombinant His6-tagged wild-type and mutant enzymes from Escherichia coli strain BL21(DE3) by nickel affinity chromatography | Homo sapiens |
Specific Activity [micromol/min/mg]
| EC Number | Specific Activity Minimum [µmol/min/mg] | Specific Activity Maximum [µmol/min/mg] | Comment | Organism |
|---|---|---|---|---|
| 1.3.8.6 | 5 | - |
recombinant mutant R227P with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 1.3.8.6 | 70 | - |
recombinant mutant V400M with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 1.3.8.6 | 112 | - |
recombinant mutant R227P with PMS, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 1.3.8.6 | 205 | - |
recombinant wild-type enzyme with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 1.3.8.6 | 1683 | - |
recombinant mutant V400M with PMS, pH 7.8, temperature not specified in the publication | Homo sapiens |
| 1.3.8.6 | 2224 | - |
recombinant wild-type enzyme with PMS, pH 7.8, temperature not specified in the publication | Homo sapiens |
Substrates and Products (Substrate)
| EC Number | Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
|---|---|---|---|---|---|---|---|
| 1.3.8.6 | glutaryl-CoA + electron-transfer flavoprotein | overall reaction | Homo sapiens | crotonyl-CoA + CO2 + reduced electron-transfer flavoprotein | - |
? | |
| 1.3.8.6 | 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 | Homo sapiens | ? | - |
- |
|
Synonyms
| EC Number | Synonyms | Comment | Organism |
|---|---|---|---|
| 1.3.8.6 | GCDH | - |
Homo sapiens |
| 1.3.8.6 | glutaryl-CoA dehydrogenase | - |
Homo sapiens |
Temperature Stability [°C]
| EC Number | Temperature Stability Minimum [°C] | Temperature Stability Maximum [°C] | Comment | Organism |
|---|---|---|---|---|
| 1.3.8.6 | 43 | 53 | apparent thermal denaturation midpoint (Tm) of GCDH wild -type and mutants using different techniques, overview | Homo sapiens |
Turnover Number [1/s]
| EC Number | Turnover Number Minimum [1/s] | Turnover Number Maximum [1/s] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.3.8.6 | 0.6 | - |
glutaryl-CoA | recombinant mutant R227P with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 1.3.8.6 | 1.3 | - |
glutaryl-CoA | recombinant mutant V400M with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 1.3.8.6 | 3.1 | - |
glutaryl-CoA | recombinant wild-type enzyme with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
pH Optimum
| EC Number | pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
|---|---|---|---|---|
| 1.3.8.6 | 7.8 | - |
assay at | Homo sapiens |
Cofactor
| EC Number | Cofactor | Comment | Organism | Structure |
|---|---|---|---|---|
| 1.3.8.6 | electron transferring flavoprotein | ETF, the GCDH natural electron acceptor | Homo sapiens | |
| 1.3.8.6 | FAD | wild-type and mutant FAD binding structures, overview | Homo sapiens | |
| 1.3.8.6 | additional information | kinetics of flavin release, overview | Homo sapiens | |
| 1.3.8.6 | phenazine methosulfate | PMS, an artificial electron acceptor | Homo sapiens | |
General Information
| EC Number | General Information | Comment | Organism |
|---|---|---|---|
| 1.3.8.6 | 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 | Homo sapiens |
| 1.3.8.6 | metabolism | glutaryl-CoA dehydrogenase (GCDH), a flavoprotein, is involved in the metabolism of tryptophan, lysine and hydroxylysin | Homo sapiens |
| 1.3.8.6 | additional information | structure comparisons of wild-type and mutant enzyme proteins, FAD binding structures, overview | Homo sapiens |
kcat/KM [mM/s]
| EC Number | kcat/KM Value [1/mMs-1] | kcat/KM Value Maximum [1/mMs-1] | Substrate | Comment | Organism | Structure |
|---|---|---|---|---|---|---|
| 1.3.8.6 | 18.4 | - |
glutaryl-CoA | recombinant mutant R227P with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 1.3.8.6 | 65 | - |
glutaryl-CoA | recombinant mutant V400M with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
| 1.3.8.6 | 146.92 | - |
glutaryl-CoA | recombinant wild-type enzyme with ETF, pH 7.8, temperature not specified in the publication | Homo sapiens | |
Use of this online version of BRENDA is free under the CC BY 4.0 license. See terms of use for full details.
Release 2023.1 (January 2023)
Legal
Curated at
Member of
