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K1502

Sigma-Aldrich

α-Ketoglutarate Dehydrogenase from porcine heart

buffered aqueous glycerol solution, 0.1-1.0 units/mg protein (Lowry)

Synonym(s):

Multienzyme 2-oxoglutarate dehydrogenase complex

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About This Item

CAS Number:
Enzyme Commission number:
MDL number:
UNSPSC Code:
12352204
NACRES:
NA.54

form

buffered aqueous glycerol solution

specific activity

0.1-1.0 units/mg protein (Lowry)

foreign activity

pyruvate dehydrogenase ≤20%

shipped in

dry ice

storage temp.

−20°C

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General description

Research Area: Neuroscience

α-Ketoglutarate dehydrogenase (α-KGDH) is a multienzyme complex localized to the mitochondria. This integrated enzyme is made up of many units of thiamine pyrophosphate-dependent dehydrogenase (E1), dihydrolipoamide dehydrogenase (E3), and dihydrolipoamide succinyl transferase (E2).

Application

α-Ketoglutarate Dehydrogenase from the porcine heart has been used:
  • to study the reversal of nitration by glutathione (GSH) in peroxynitrite-treated cells
  • to measure its activity by Spectramax M5 microplate spectrofluorimeter using heart mitochondria
  • as a positive control to evaluate its activity in by Spectramax GEMINI EM fluorescence microplate reader using mice neurons

Biochem/physiol Actions

α-Ketoglutarate dehydrogenase (α-KGDH) is a key enzyme of bioenergetic processes and a controlling unit of metabolic flux through the Krebs cycle or tricarboxylic acid (TCA) cycle. It catalyzes the oxidative decarboxylation of α-ketoglutarate (KG) to succinyl-CoA by releasing reduced nicotinamide adenine dinucleotide (NADH). It is the rate-limiting reaction of the TCA cycle. This reaction contributes to the electrons of the respiratory chain and requires thiamine pyrophosphate as a cofactor. The reduction of NAD (nicotinamide adenine dinucleotide) is observed to determine its reaction rate. α-KGDH from porcine has an optimum pH range of 6.6–7.4. This enzyme is inhibited by oxidative stress and results in a metabolic deficiency. However, α-KGDH is also known to produce reactive oxygen species (ROS) leading to oxidative stress. Defective or limited levels of α-KGDH cause several neurodegenerative diseases such as Alzheimer′s disease.
α-Ketoglutarate dehydrogenase is most responsive to alterations in the tumor microenvironment and contributes to the adaptive metabolic response in cancer. Inhibiting α-ketoglutarate dehydrogenase counteracts lung metastasis associated with breast cancer.

Quality

May contain traces of polyethylene glycol.

Unit Definition

One unit will convert 1.0 μmole of β-NAD to β-NADH per min at pH 7.4 at 30 °C in the presence of saturating levels of coenzyme A.

Physical form

Supplied as a 50% glycerol solution containing ~9 mg per mL bovine serum albumin, 30% sucrose, 1.5 mM EDTA, 1.5 mM EGTA, 1.5 mM 2-mercaptoethanol, 0.3% TRITON X-100, 0.003% sodium azide, and 15 mM potassium phosphate, pH 6.8.

Legal Information

Triton is a trademark of The Dow Chemical Company or an affiliated company of Dow

Hazard Statements

Precautionary Statements

Hazard Classifications

Aquatic Chronic 3

Storage Class Code

10 - Combustible liquids

WGK

WGK 1

Flash Point(F)

Not applicable

Flash Point(C)

Not applicable

Personal Protective Equipment

dust mask type N95 (US), Eyeshields, Gloves

Certificates of Analysis (COA)

Search for Certificates of Analysis (COA) by entering the products Lot/Batch Number. Lot and Batch Numbers can be found on a product’s label following the words ‘Lot’ or ‘Batch’.

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Shuyi Zhang et al.
Science (New York, N.Y.), 334(6062), 1551-1553 (2011-12-17)
It is generally accepted that cyanobacteria have an incomplete tricarboxylic acid (TCA) cycle because they lack 2-oxoglutarate dehydrogenase and thus cannot convert 2-oxoglutarate to succinyl-coenzyme A (CoA). Genes encoding a novel 2-oxoglutarate decarboxylase and succinic semialdehyde dehydrogenase were identified in
alpha-ketoglutarate dehydrogenase inhibition counteracts breast cancer-associated lung metastasis
Atlante S, et al.
Cell Death & Disease, 9(7), 756-756 (2018)
Wagner L Araújo et al.
The Plant cell, 24(6), 2328-2351 (2012-07-04)
Transgenic tomato (Solanum lycopersicum) plants expressing a fragment of the gene encoding the E1 subunit of the 2-oxoglutarate dehydrogenase complex in the antisense orientation and exhibiting substantial reductions in the activity of this enzyme exhibit a considerably reduced rate of
Laszlo Tretter et al.
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 360(1464), 2335-2345 (2005-12-03)
Alpha-ketoglutarate dehydrogenase (alpha-KGDH) is a highly regulated enzyme, which could determine the metabolic flux through the Krebs cycle. It catalyses the conversion of alpha-ketoglutarate to succinyl-CoA and produces NADH directly providing electrons for the respiratory chain. alpha-KGDH is sensitive to
Lidan Sun et al.
Journal of neurochemistry, 158(2), 282-296 (2021-04-28)
Metabolic changes that correlate to cognitive changes are well-known in Alzheimer's disease (AD). Metabolism is often linked to functional changes in proteins by post-translational modifications. The importance of the regulation of transcription by acetylation is well documented. Advanced mass spectrometry

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