Succinic Dehydrogenase: A Detailed Overview

Succinic dehydrogenase, or SDH, is an enzyme that plays a vital role in many biological processes in the body, including energy production and cell respiration. In this article, we will explore the structure, mechanism, role, importance, regulation and diseases associated with this essential enzyme.

Structure and Mechanism of succinic dehydrogenase

SDH is a heterotetramer made up of a combination of four different subunits. These subunits are alpha subunit, beta psubunit, beta prime subunit, and a gamma subunit, but the exact makeup of the enzyme can differ from organism to organism. SDH carries out the oxidation-reduction of succinate to fumarate as part of its catalytic cycle, and utilizes a flavin adenine dinucleotide (FAD) as a cofactor.

Role of succinic dehydrogenase

SDH is a crucial enzyme in the Krebs Cycle, where it is responsible for the reduction of succinate to fumarate. Not only is this reaction necessary for energy production in the form of ATP, but it is also critical for other metabolic reactions to occur in cells.

Importance of succinic dehydrogenase

The importance of SDH can’t be overstated. Its role in the Krebs Cycle has a dramatic effect on energy production, as well as other metabolic pathways. Additionally, SDH is used to transport electrons from succinate to the electron transport chain for eventual release as ATP.

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This enzyme is found in the cytoplasm of both eukaryotes and prokaryotes, and it catalyzes the oxidation of succinate to fumarate.

SDH also plays an important role in the regulation of mitochondrial respiration and the transfer of electrons from succinate to the electron transport chain.

The disruption of SDH activity can lead to an imbalance in the electron transport chain, resulting in the production of reactive oxygen species and other oxidative stress-related conditions.

Moreover, SDH has been found to be involved in the regulation of cholesterol metabolism, angiogenesis, and cell cycle progression.

The disruption of its function has been associated with the development of several cancers, including colon, stomach, and prostate.

In addition, it has been observed to play a role in the protection of cells from oxidative damage, as well as modulating the cell’s response to inflammation.

Overall, it’s clear that SDH is essential for a variety of important biological processes and that disruption of its activity can lead to serious health problems.

Regulation of succinic dehydrogenase

The expression and activity of SDH is regulated by both environmental and internal cues. For instance, it is known to be inhibited at both very low and very high concentrations of succinate, as well as by hormones such as insulin. Likewise, its expression can be modulated by factors such as heat shock and nutrient availability.

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Diseases

SDH deficiencies have been linked to a number of diseases and disorders, such as Paraganglioma, Neuroblastoma and Leigh Syndrome. In these disorders, there can be mutations in one or more of the subunits of the enzyme, leading to a decrease in its activity.

Causes of succinate deficiency

Succinate deficiency is a genetic disorder that impacts the body’s ability to use succinate, a naturally-occurring metabolite. It is caused by mutations in the SDHA, SDHB, SDHC and SDHD genes that code for subunits of enzymes in the mitochondrion, leading to reduced activity of the succinate dehydrogenase (SDH) enzyme complex. This causes an accumulation of succinyl-CoA in the mitochondrion and prevents the proper use of succinate throughout the body. Symptoms of succinate deficiency can vary from mild to severe and may include muscular weakness, fatigue, exercise intolerance and cognitive impairment.

When SDHA or SDHB are affected, patients may experience additional problems with diabetes, hearing impairment, cardiomyopathy and respiratory failure due to impaired oxidative phosphorylation. Other complications related to succinate deficiency are elevated levels of lactic and pyruvic acid in the blood, kidney impairment and complications with vision. Patients may require a combination of treatments and therapies such as dietary changes, medications, enzyme replacement therapy, and physical, occupational and speech therapies.

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The cause of succinate deficiency is genetic mutations in the four SDH genes, leading to the reduction of activity of the SDH enzyme complex. The mutation may be inherited from either parent, or it can be the result of a spontaneous mutation in the intervening testicular or ovarian cells after fertilization.

It is essential to diagnose succinate deficiency early as complications, such as respiratory and cardiac failure, can be fatal. A combination of diagnosis methods such as genetic testing, blood tests, imaging scans and biopsies may be used to accurately diagnose the condition and determine an effective treatment plan.

Succinate deficiency is a rare but potentially fatal genetic disorder. Treatment is focused on providing support for the affected area and addressing symptoms. Early diagnosis is key to improving quality of life and reducing the risk of fatal complications.

Conclusion

The essential enzyme succinic dehydrogenase is critical for energy production and other cell respiration processes. This article has explored its structure, mechanism, role, importance, regulation and diseases associated with SDH. Despite its small size, SDH is an incredibly important component of the human body.