1.2.1.105: 2-oxoglutarate dehydrogenase system
This is an abbreviated version!
For detailed information about 2-oxoglutarate dehydrogenase system, go to the full flat file.
Word Map on EC 1.2.1.105
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1.2.1.105
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kgdhc
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dihydrolipoamide
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thiamin
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alpha-ketoacids
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2-oxoadipate
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transsuccinylase
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charcot-marie-tooth
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2-aminoadipic
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medicine
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thiokinase
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glutaryl-coa
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analysis
- 1.2.1.105
- kgdhc
- dihydrolipoamide
- thiamin
- alpha-ketoacids
- 2-oxoadipate
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transsuccinylase
- charcot-marie-tooth
-
2-aminoadipic
- medicine
- thiokinase
- glutaryl-coa
- analysis
Reaction
Synonyms
2-OGDH2, 2-oxoglutarate dehydrogenase, 2-oxoglutarate dehydrogenase complex, alpha-KDE2, alpha-ketoglutarate dehydrogenase, alpha-ketoglutarate dehydrogenase complex, alpha-KGDH, At3g55410, At5g65750, DHTKD1, dihydrolipoyl succinyltransferase E2, E1a, E1k, E1o, E2, KGDH, KGDHC, More, MPA24.10, ODGH, ODGH1, ODGH2, ODH, OGDC, OGDH, OGDHC, OGDHL, OGHDC-E2, PDHC, SucA, SucB
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1.2.1.105 2-oxoglutarate dehydrogenase systemAdvanced search results
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General Information on EC 1.2.1.105 - 2-oxoglutarate dehydrogenase system
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GENERAL INFORMATION 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
malfunction
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RNAi knockdown-inducted bloodstream trypanosomes show pronounced growth reduction and often fail to equally distribute kinetoplast DNA to daughter cells, resulting in accumulation of cells devoid of kinetoplast DNA or containing two kinetoplasts
metabolism
hE1o can also utilize 2-oxoadipate (OA) as a substrate. Both E1o-specific and overall complex activities (NADH production) are detected using OA as a substrate. hE1o forms the thiamine diphosphate-enamine and the C2alpha-hydroxyalkyl-thiamine diphosphate with nearly identical rates for 2-oxoglutarate OG and OA, and both OG and OA can reductively acylate lipoyl domain created from dihydrolipoyl succinyltransferase (E2o). Dioxygen can oxidize the thiamine diphosphate-derived enamine from both OG and OA, leading to thiamine diphosphate-enamine radical and generation of superoxide and H2O2. The efficiency of superoxide/H2O2 production is 7-times larger from OA than from OG
physiological function
physiological function
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the enzyme is bifunctional, both as a metabolic enzyme and as a mitochondrial inheritance factor necessary for the distribution of kinetoplast DNA networks to daughter cells at cytokinesis
physiological function
a hybrid complex consisting of E1p (thiamine diphosphate-dependent pyruvate dehydrogenase, AceE), E2 (dihydrolipoamide acetyltransferase, AceF), E3 (dihydrolipoamide dehydrogenase, Lpd), and E1o (thiamine diphosphate-dependent 2-oxoglutarate dehydrogenase, OdhA) contains six copies of E2 in its core. E2 forms a stable complex with E3 (E2-E3 subcomplex) in vitro, hypothetically comprised of two E2 trimers and four E3 dimers. E1o exists mainly as a hexamer in solution and is ready to form an active ODH complex when mixed with the E2-E3 subcomplex. In vitro, there is E1p- and E1o-dependent inhibition of ODH and PDH, respectively, actively supporting the formation of the hybrid complex, in which both E1p and E1o associate with a single E2-E3
physiological function
functional and regulatory crosstalk between the 2-oxoglutarate dehydrogenase complex, and a 2-oxoadipate dehydrogenase complex from the final degradation pathway of L-lysine, L-hydroxylysine and L-tryptophan. The two complexes share the same dihydrolipoyl succinyltransferase (E2) and dihydrolipoyl dehydrogenase (E3) components but display different substrate preferences and different binding modes. Similarly to E1o, the E1a also forms the thiamine diphosphate-enamine radical from 2-oxoadipate in the oxidative half reaction. Both complexes produced superoxide/H2O2 from O2 in the reductive half reaction
physiological function
hybrid complexes consisting of recombinant components of OGDHc and pyruvate dehydrogenase enzymes suggest that a different component is the gatekeeper for specificity for the two multienzyme complexes in bacteria, the E1 component for pyruvate, but the E2 component for 2-oxoglutarate
physiological function
mitochondrial hydrolase ABHD11 signals changes in mitochondrial 2-oxoglutarate metabolism. ABHD11 loss or inhibition drives a rapid increase in 2-oxoglutarate levels by impairing lipoylation of the 2-oxoglutarate dehydrogenase complex. ABHD11 associates with the OGDHc and maintains catalytic activity of lipoyl domain by preventing the formation of lipoyl adducts
physiological function
mutant plants lacking component E1 isoform OGDH1 or OGDH2 exhibit substantial reduction in both respiration and CO2 assimilation rates. Mutant lines exhibit reduced levels of chlorophylls and nitrate, increased levels of sucrose, malate and fumarate and minor changes in total protein and starch levels in leaves. After 4 weeks of growth, a clear decrease in the shoot growth of the OGDH1 mutant lines is observed, while OGDH2 mutant lines exhibit increased growth in comparison to wild type plants. The leaf number is unaltered in OGDH1 mutant lines and increased in OGDH2 mutant lines. Repression of the OGDH1 gene leads to a significative reduction of silique length and the number of seeds per silique. Lack of expression of the OEGDH2 gene does not affect the silique length, but decreases the number of seeds per silique. Isoform OGDH1 is essential to the final 2-OGDH activity in leaves while isoform OGDH2 is not
physiological function
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organisms possessing OGDHC respond to succinyl phosphonate inhibition by significantly changing their amino acid pools. Increases in Glu, 4-aminobutanoate and alanine represent the most universal change, and strong perturbation in the relative abundance of amino acids due to the OGDHC inhibition is accompanied by decreased protein content
physiological function
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organisms possessing OGDHC respond to succinyl phosphonate inhibition by significantly changing their amino acid pools. Increases in Glu, 4-aminobutanoate and alanine represent the most universal change, and strong perturbation in the relative abundance of amino acids due to the OGDHC inhibition is accompanied by decreased protein content
physiological function
protein-protein interactions in the dehydrogenase complex. Fluorescence studies suggest a strong interaction for the E1-E2 subcomplex, but a much weaker interaction in the E1-E3 subcomplex, and fail to identify any interaction in the E2-E3 subcomplex. Hydrogen-deuterium exchange MS studies show interactions in the E1-E2 and E1-E3. The N-terminal region of E1, peptides 18YVEEM22 and 27ENPKSVHKSWDIF39 constitute the binding region responsible for the assembly of the E1 with both the E2 and E3 components into OGDH. A E2 region comprising residues from both a linker region and from the catalytic domain is critical for interacting with E1
physiological function
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enzymes purified from skeletal muscle of euthermic and hibernating ground squirrels are evaluated at 5°C, 22°C, and 37 °C. The enzyme complex from hibernator muscle at all temperatures compared with euthermic controls exhibits a decreased affinity for CoA as well as reduced activation by Ca2+ ions at 5°C from both euthermic and hibernating conditions. The E1, E2 and E3 enzymes of the complex (OGDH, DLST, DLD) all show elevated phosphotyrosine content during hibernation as well as increased ADP-ribosylation and succinylation of hibernator OGDH
physiological function
the 2-oxoadipate dehydrogenase E1a uses the dihydrolipoyl succinyltransferase (E2o) and the dihydrolipoyl dehydrogenase (E3) components of the tricarboxylic acid cycle 2-oxoglutarate dehydrogenase complex (OGDHc) for its activity. 2-Oxoglutarate and 2-oxoadipate can be oxidized by E1a, E1a displays an approximately 49fold preference in catalytic efficiency for 2-oxoadipate over 2-oxoglutarate. E1a forms the thiamidiphosphate-enamine radical from 2-oxoadipate in the oxidative half reaction, and may produce superoxide and H2O2 from decarboxylation of 2-oxoadipate in the forward physiological direction. Once assembled to complex with the same E2o and E3 components, the E1o and E1a display strikingly different regulation: both succinyl-CoA and glutaryl-CoA significantly reduced the E1o activity, but not the activity of E1a
physiological function
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the enzyme mediates the inhibition of SIRT5 on cell proliferation and migration of gastric cancer
physiological function
the OGDH complex behaves as a 2-oxoadipate dehydrogenase, in addition to its usual 2-oxoglutarate dehydrogenase activity. Human E1o by itself and when assembled into the OGDH complex can serve as a source of superoxide/H2O2 generation in mitochondria from 2-oxoadipate. A H2O2 generating activity from 2-oxoadipate of 2.668 nmol/min/mg hE1o is estimated for assembled OGDH complex and is more than 7fold higher than that with 2-oxoglutarate
physiological function
two genes encode for the E1 subunit of 2-OGDH. Insertion knockout mutant lines for each of the genes exhibit substantial reduction in both respiration and CO2 assimilation rates. Mutant lines exhibit reduced levels of chlorophylls and nitrate, increased levels of sucrose, malate and fumarate and minor changes in total protein and starch levels in leaves. Absence in expression of E1-OGDH2 gene does not affect the silique length, but decreased the number of seeds per silique. In seedlings lacking only the expression of E1-OGDH2 the root growth is invariant from that of wild type seedlings
physiological function
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a hybrid complex consisting of E1p (thiamine diphosphate-dependent pyruvate dehydrogenase, AceE), E2 (dihydrolipoamide acetyltransferase, AceF), E3 (dihydrolipoamide dehydrogenase, Lpd), and E1o (thiamine diphosphate-dependent 2-oxoglutarate dehydrogenase, OdhA) contains six copies of E2 in its core. E2 forms a stable complex with E3 (E2-E3 subcomplex) in vitro, hypothetically comprised of two E2 trimers and four E3 dimers. E1o exists mainly as a hexamer in solution and is ready to form an active ODH complex when mixed with the E2-E3 subcomplex. In vitro, there is E1p- and E1o-dependent inhibition of ODH and PDH, respectively, actively supporting the formation of the hybrid complex, in which both E1p and E1o associate with a single E2-E3
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