Unlocking the Potential of Succinate Dehydrogenase Complex: A Promising Drug Target and Biomarker

Target Name: Succinate Dehydrogenase Complex

NCBI ID: P9338

Other Name(s): Succinate-coenzyme Q reductase (SQR) | Respiratory Complex II

Unlocking the Potential of Succinate Dehydrogenase Complex: A Promising Drug Target and Biomarker

Succinate Dehydrogenase Complex (S succinyl-CoA Reductase, SQR) is a crucial enzyme in the citric acid cycle, also known as the Krebs cycle or tricarboxylic acid (TCA) cycle, which is a central metabolic pathway for cell energy production.1 SQR catalyzes the conversion of succinyl-CoA, a key intermediate in the TCA cycle, to succinyl-CoA derivatives that can be used for energy production or other cellular processes.2,3

SQR has been identified as a potential drug target due to its unique mechanism of action and its involvement in various diseases, including cancer,4,5 neurodegenerative diseases,6,7 and metabolic disorders.8,9 In this article, we will explore the SQR and its potential as a drug target, as well as its role as a biomarker for disease diagnosis and monitoring.

The SQR Enzyme

SQR is a member of the superfamily of Coenzyme A (CoA)ases, which include other well-known enzymes such as FAD and NAD+-dependent CoA enzymes.8,9 SQR has four distinct subunits, named SQR1, SQR2, SQR3, and SQR4, which are responsible for catalyzing the different stages of the SQR reaction.10

The SQR reaction starts with succinyl-CoA, which is converted to succinyl-CoA hydrolase (SQR1), which optimizes the conversion rate by reducing the affinity of the substrate for the active site.11 SQR2 then catalyzes the conversion of succinyl-CoA hydrolase products to succinyl-CoA, which is then converted to succinyl-CoA synthase (SQR3) via a second reduction step.12

SQR4 is responsible for the final step of the SQR reaction, where succinyl-CoA is converted to succinyl-CoA sulfate, which is then excreted from the cell.13

SQR's Role in Disease

SQR has been implicated in various diseases due to its involvement in the TCA cycle and the production of succinyl-CoA derivatives.4,5,8,9,10

1. Cancer
SQR has been shown to be involved in the regulation of cell growth and differentiation, which are critical processes for cancer development.14 SQR has been shown to inhibit the inhibitor of DNA binding (ID4), which is a negative regulator of SQR activity.15,16

1. Neurodegenerative Diseases
SQR has been implicated in the development and progression of neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease.17 SQR has been shown to modulate the levels of neurotransmitters, such as dopamine and nitric oxide, which are involved in the progression of neurodegenerative diseases.18

1. Metabolic Disorders
SQR has been implicated in the regulation of cellular metabolism, including energy metabolism.19 SQR has been shown to play a role in the metabolism of fatty acids, which are crucial for maintaining cellular energy production.20

Potential Therapeutic Strategies

SQR has been identified as a potential drug target due to its unique mechanism of action and its involvement in various diseases.21,22 Several strategies have been proposed to target SQR, including inhibition of SQR1,23 inhibition of SQR2,24 and inhibition of SQR4.25,26

1. Inhibition of SQR1
SQR1 is the rate-limiting step in the SQR reaction, and inhibition

Protein Name: Succinate Dehydrogenase Complex

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