Oxoglutarate dehydrogenase
Encyclopedia
The oxoglutarate dehydrogenase complex (OGDC) or α-ketoglutarate dehydrogenase complex is an enzyme complex, most commonly known for its role in the citric acid cycle
.
In fact, three classes of these multienzyme complexes have been characterized, one specific for pyruvate, a second specific for 2-oxoglutarate, and a third specific for branched-chain α-keto acids.
(1):
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This reaction proceeds in three steps:
ΔG°'
for this reaction is -7.2 kcal mol-1. The energy needed for this oxidation is conserved in the formation of a thioester bond of succinyl CoA.
, a form of acute liver failure. These antibodies appear to recognize oxidized protein
that has resulted from inflammatory immune responses. Some of
these inflammatory responses are explained by gluten sensitivity
. Other mitochondrial autoantigens
include pyruvate dehydrogenase
and branched-chain alpha-keto acid dehydrogenase complex
, which are antigens recognized by anti-mitochondrial antibodies
.
Activity of the 2-oxoglutarate dehydrogenase complex is decreased in many neurodegenerative diseases.
Citric acid cycle
The citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
.
Units
Much like pyruvate dehydrogenase complex (PDC), this enzyme forms a complex composed of three components:| Unit | EC number | Name | Gene | Coenzyme >- | E1 |
oxoglutarate dehydrogenase | OGDH OGDH Alpha-ketoglutarate dehydrogenase also known as 2-oxoglutarate dehydrogenase E1 component, mitochondrial is an enzyme that in humans is encoded by the OGDH gene.- Function :This gene encodes one subunit of the 2-oxoglutarate dehydrogenase complex... |
thiamine pyrophosphate Thiamine pyrophosphate Thiamine pyrophosphate , or thiamine diphosphate , is a thiamine derivative which is produced by the enzyme thiamine pyrophosphatase. Thiamine pyrophosphate is a coenzyme that is present in all living systems, in which it catalyzes several biochemical reactions... >- | E2 |
dihydrolipoyl succinyltransferase | DLST DLST Dihydrolipoyllysine-residue succinyltransferase component of 2-oxoglutarate dehydrogenase complex, mitochondrial is an enzyme that in humans is encoded by the DLST gene.- Interactive pathway map :-Further reading:... |
lipoic acid Lipoic acid Lipoic acid , also known as α-lipoic acid and Alpha Lipoic Acid is an organosulfur compound derived from octanoic acid. LA contains two vicinal sulfur atoms attached via a disulfide bond and is thus considered to be oxidized... >- | E3 |
dihydrolipoyl dehydrogenase | DLD Dihydrolipoamide dehydrogenase Dihydrolipoamide dehydrogenase , also known as dihydrolipoyl dehydrogenase, mitochondrial, is an enzyme that in humans is encoded by the DLD gene. DLD is a flavoprotein enzyme that degrades lipoamide, and produces dihydrolipoamide.... |
FAD FAD In biochemistry, flavin adenine dinucleotide is a redox cofactor involved in several important reactions in metabolism. FAD can exist in two different redox states, which it converts between by accepting or donating electrons. The molecule consists of a riboflavin moiety bound to the phosphate... |
In fact, three classes of these multienzyme complexes have been characterized, one specific for pyruvate, a second specific for 2-oxoglutarate, and a third specific for branched-chain α-keto acids.
Metabolic pathways
This enzyme participates in three different pathways:- Citric acid cycleCitric acid cycleThe citric acid cycle — also known as the tricarboxylic acid cycle , the Krebs cycle, or the Szent-Györgyi-Krebs cycle — is a series of chemical reactions which is used by all aerobic living organisms to generate energy through the oxidization of acetate derived from carbohydrates, fats and...
(KEGG link: MAP00020) - LysineLysineLysine is an α-amino acid with the chemical formula HO2CCH4NH2. It is an essential amino acid, which means that the human body cannot synthesize it. Its codons are AAA and AAG....
degradation (KEGG link: MAP00310) - TryptophanTryptophanTryptophan is one of the 20 standard amino acids, as well as an essential amino acid in the human diet. It is encoded in the standard genetic code as the codon UGG...
metabolism (KEGG link: MAP00380)
Kinetic properties
The following values are from Azotobacter vinelandiiAzotobacter vinelandii
Azotobacter vinelandii is diazotroph that can fix nitrogen while grown aerobically. It is a genetically tractable system that is used to study nitrogen fixation...
(1):
- KMMichaelis-Menten kineticsIn biochemistry, Michaelis–Menten kinetics is one of the simplest and best-known models of enzyme kinetics. It is named after German biochemist Leonor Michaelis and Canadian physician Maud Menten. The model takes the form of an equation describing the rate of enzymatic reactions, by relating...
: 0.14 ± 0.04 mM - Vmax : 9 ± 3 μmol.min-1.mg-1
Reaction
The reaction catalyzed by this enzyme in the citric acid cycle is:- α-ketoglutarate + NAD+Nicotinamide adenine dinucleotideNicotinamide adenine dinucleotide, abbreviated NAD, is a coenzyme found in all living cells. The compound is a dinucleotide, since it consists of two nucleotides joined through their phosphate groups. One nucleotide contains an adenine base and the other nicotinamide.In metabolism, NAD is involved...
+ CoACoenzyme ACoenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
→ Succinyl CoA + CO2Carbon dioxideCarbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
+ NADH
- decarboxylationDecarboxylationDecarboxylation is a chemical reaction that releases carbon dioxide . Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is the first chemical step in photosynthesis, is called carbonation, the addition of CO2 to...
of α-ketoglutarate, - reductionRedoxRedox reactions describe all chemical reactions in which atoms have their oxidation state changed....
of NAD+ to NADH, - and subsequent transfer to CoACoenzyme ACoenzyme A is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All sequenced genomes encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it as a substrate...
, which forms the end product, succinyl CoA.
ΔG°'
Gibbs free energy
In thermodynamics, the Gibbs free energy is a thermodynamic potential that measures the "useful" or process-initiating work obtainable from a thermodynamic system at a constant temperature and pressure...
for this reaction is -7.2 kcal mol-1. The energy needed for this oxidation is conserved in the formation of a thioester bond of succinyl CoA.
Regulation
Oxoglutarate dehydrogenase is a key control point in the citric acid cycle. It is inhibited by its products, succinyl CoA and NADH. A high energy charge in the cell will also be inhibitive. ADP and calcium ions are allosteric activators of the enzyme.Pathology
2-Oxo-glutarate dehydrogrenase is an autoantigen recognized in primary biliary cirrhosisPrimary biliary cirrhosis
Primary biliary cirrhosis, often abbreviated PBC, is an autoimmune disease of the liver marked by the slow progressive destruction of the small bile ducts within the liver. When these ducts are damaged, bile builds up in the liver and over time damages the tissue. This can lead to scarring,...
, a form of acute liver failure. These antibodies appear to recognize oxidized protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that has resulted from inflammatory immune responses. Some of
these inflammatory responses are explained by gluten sensitivity
Gluten sensitivity
Gluten sensitivity belongs to a spectrum of disorders in which gluten has an adverse effect on the body. It can be defined as a non-allergic and non-autoimmune condition in which the consumption of gluten can lead to symptoms similar to those observed in coeliac disease or wheat allergy .Gluten...
. Other mitochondrial autoantigens
include pyruvate dehydrogenase
Pyruvate dehydrogenase
Pyruvate dehydrogenase complex is a complex of three enzymes that transform pyruvate into acetyl-CoA by a process called pyruvate decarboxylation. Acetyl-CoA may then be used in the citric acid cycle to carry out cellular respiration, and this complex links the glycolysis metabolic pathway to the...
and branched-chain alpha-keto acid dehydrogenase complex
Branched-chain alpha-keto acid dehydrogenase complex
The branched-chain α-keto acid dehydrogenase complex is a combination of enzymes responsible for the degradation of the branched-chain amino acids...
, which are antigens recognized by anti-mitochondrial antibodies
Anti-mitochondrial antibodies
Anti-mitochondrial antibodies are autoantibodies, consisting of immunoglobulins formed against mitochondria, primarily mitochondria in cells of the liver...
.
Activity of the 2-oxoglutarate dehydrogenase complex is decreased in many neurodegenerative diseases.