chemistry

Oxoglutarate dehydrogenase complex

Oxoglutarate dehydrogenase complex is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Oxoglutarate dehydrogenase complex rather than just read about it. In short: The oxoglutarate dehydrogenase complex (OGDC) or α-ketoglutarate dehydrogenase complex is a mitochondrial multienzyme complex, most commonly known for its role in the citric acid cycle. It belongs to the 2-oxoacid dehydrogenase complex family.

Key takeaways

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Reference excerpt

The oxoglutarate dehydrogenase complex (OGDC) or α-ketoglutarate dehydrogenase complex is a mitochondrial multienzyme complex, most commonly known for its role in the citric acid cycle. It belongs to the 2-oxoacid dehydrogenase complex family.

Units Much like pyruvate dehydrogenase complex (PDC), this enzyme forms a complex composed of three components:

Four members of these multienzyme complexes have been characterized: one specific for pyruvate, a second specific for 2-oxoglutarate, a third specific for 2-oxoadipate, and a fourth specific for branched-chain α-keto acids. The oxoglutarate dehydrogenase complex has the same subunit structure and thus uses the same cofactors (TPP, CoA, lipoate, FAD and NAD) as:

the pyruvate dehydrogenase complex (PDHC), the 2-oxoadipate dehydrogenase complex (OADHC), and the branched-chain alpha-keto acid dehydrogenase complex (BCKDC). Among these, OGDC and OADHC are particularly closely related, as they not only share the same E2 and E3 components, but also catalyze chemically similar reactions within adjacent steps of lysine and tryptophan catabolism. Notably, all four complexes rely on a common E3 subunit that is also employed by the glycine cleavage system (GCS) in the form of its L-protein, despite the GCS not belonging to this enzyme family.

Properties

Metabolic pathways This enzyme participates in three different pathways:

Citric acid cycle (KEGG link: MAP00020 Archived 2022-03-08 at the Wayback Machine) Lysine degradation (KEGG link: MAP00310 Archived 2020-11-22 at the Wayback Machine) Tryptophan metabolism (KEGG link: MAP00380 Archived 2020-11-21 at the Wayback Machine)

Kinetic properties The following values are from Azotobacter vinelandii (1):

KM: 0.14 ± 0.04 mM Vmax : 9 ± 3 μmol.min−1.mg−1

Citric acid cycle

Reaction The reaction catalyzed by this enzyme in the citric acid cycle is:

α-ketoglutarate + NAD+ + CoA → Succinyl CoA + CO2 + NADH

This reaction proceeds in three steps:

decarboxylation of α-ketoglutarate, reduction of NAD+ to NADH, and subsequent transfer to CoA, which forms the end product, succinyl CoA. 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.

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. By controlling the amount of available reducing equivalents generated by the Krebs cycle, Oxoglutarate dehydrogenase has a downstream regulatory effect on oxidative phosphorylation and ATP production. Reducing equivalents (such as NAD+/NADH) supply the electrons that run through the electron transport chain of oxidative phosphorylation. Increased Oxoglutarate dehydrogenase activation levels serve to increase the concentrations of NADH relative to NAD+. High NADH concentrations stimulate an increase in flux through oxidative phosphorylation. While an increase in flux through this pathway generates ATP for the cell, the pathway also generates free radical species as a side product, which can cause oxidative stress to the cells if left to accumulate. Oxoglutarate dehydrogenase is considered to be a redox sensor in the mitochondria, and has an ability to change the functioning level of mitochondria to help prevent oxidative damage. In the presence of a high concentration of free radical species, Oxoglutarate dehydrogenase undergoes fully reversible free radical mediated inhibition. In extreme cases, the enzyme can also undergo complete oxidative inhibition. When mitochondria are treated with excess hydrogen peroxide, flux through the electron transport chain is reduced, and NADH production is halted. Upon consumption and removal of the free radical source, normal mitochondrial function is restored. It is believed that the temporary inhibition of mitochondrial function stems from the reversible glutathionylation of the E2-lipoac acid domain of Oxoglutarate dehydrogenase. Glutathionylation, a form of post-translational modification, occurs during times of increased concentrations of free radicals, and can be undone after hydrogen peroxide consumption via glutaredoxin. Glutathionylation "protects" the lipoic acid of the E2 domain from undergoing oxidative damage, which helps spare the Oxoglutarate dehydrogenase complex from oxidative stress. Oxoglutarate dehydrogenase activity is turned off in the presence of free radicals in order to protect the enzyme from damage. Once free radicals are consumed by the cell, the enzyme's activity is turned back on via glutaredoxin. The reduction in activity of the enzyme under times of oxidative stress also serves to slow the flux through the electron transport chain, which slows production of free radicals. In addition to free radicals and the mitochondrial redox state, Oxoglutarate dehydrogenase activity is also regulated by ATP/ADP ratios, the ratio of Succinyl-CoA to CoA-SH, and the concentrations of various metal ion cofactors (Mg2+, Ca2+). Many of these allosteric regulators act at the E1 domain of the enzyme complex, but all three domains of the enzyme complex can be allosterically controlled. The activity of the enzyme complex is upregulated with high levels of ADP and Pi, Ca2+, and CoA-SH. The enzyme is inhibited by high ATP levels, high NADH levels, and high Succinyl-CoA concentrations.

… excerpt ends here. Continue reading the full article.

Illustrations

Worked examples

Example 1 — a first encounter with Oxoglutarate dehydrogenase complex

Start with the simplest possible case. Write down what Oxoglutarate dehydrogenase complex claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Oxoglutarate dehydrogenase complex before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Oxoglutarate dehydrogenase complex ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Oxoglutarate dehydrogenase complex

In research: Oxoglutarate dehydrogenase complex appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Oxoglutarate dehydrogenase complex in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Oxoglutarate dehydrogenase complex is common in secondary-school and first-year university syllabi. It links to neighbouring topics Autoantigens, Citric acid cycle, EC 1.2.4, so understanding it makes those chapters shorter.
In everyday life: Look for Oxoglutarate dehydrogenase complex outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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Frequently asked questions

What is Oxoglutarate dehydrogenase complex in simple terms?

Why does Oxoglutarate dehydrogenase complex matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Oxoglutarate dehydrogenase complex?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

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