ACOD1 - Cis-aconitate decarboxylase | Elisa - Clia - Antibody - Protein

Background

ACOD1, also known as cis-aconitate decarboxylase, is an enzyme that plays a crucial role in cellular metabolism, particularly in the regulation of immune responses. The gene is officially designated as ACOD1, but it is also referred to as IRG1 (Immune-responsive gene 1). ACOD1 catalyzes the conversion of cis-aconitate to itaconate through a decarboxylation reaction. This reaction involves the removal of a carboxyl group from cis-aconitate, resulting in the formation of itaconate. This enzymatic activity is essential for the metabolic pathway known as the itaconate pathway. Itaconate is considered an immunometabolite, meaning it has both metabolic and immunological functions. It plays a role in modulating immune responses, particularly by regulating the production of inflammatory cytokines and reactive oxygen species (ROS) Itaconate, the product of ACOD1 enzymatic activity, has been shown to have immunomodulatory properties. It can inhibit the activity of enzymes involved in inflammatory pathways, such as succinate dehydrogenase and inhibitor of nuclear factor kappa-B kinase subunit epsilon (IKKε). By doing so, it can dampen excessive inflammation and promote immune homeostasis. Dysregulation of ACOD1 expression or itaconate metabolism has been implicated in various diseases, including inflammatory disorders, infectious diseases, and metabolic diseases. Studies have highlighted the therapeutic potential of targeting ACOD1 and itaconate metabolism for the treatment of such conditions.

Protein Structure

The structural features of ACOD1 include:

• Catalytic Domain: Contains the active site responsible for the decarboxylation of cis-aconitate.
• Substrate Binding Sites: Specific regions that bind cis-aconitate and position it correctly for the decarboxylation reaction.
• Regulatory Motifs: May include regions for regulation by post-translational modifications such as phosphorylation, influencing its activity under different cellular conditions.

Classification and Subtypes

ACOD1 is classified based on its enzymatic function in the TCA cycle and immune response. It does not have widely recognized subtypes but is often referred to in the context of its dual role as a metabolic enzyme and an immune modulator.

Function and Biological Significance

ACOD1 serves several important functions in cellular metabolism and immune regulation:

1. Itaconate Production: Catalyzes the conversion of cis-aconitate to itaconate, which has antimicrobial and anti-inflammatory properties.
2. Immune Response Modulation: Itaconate produced by ACOD1 inhibits succinate dehydrogenase, modulating the TCA cycle and reducing the production of pro-inflammatory cytokines.
3. Antimicrobial Activity: Itaconate can inhibit the growth of various pathogens, including bacteria and fungi, by disrupting their metabolic processes.
4. Regulation of Inflammation: Itaconate modulates the inflammatory response by inhibiting pathways such as NF-κB and NLRP3 inflammasome activation.

Interactions

ACOD1 interacts with various molecules and pathways to execute its functions:

1. Cis-Aconitate: The primary substrate for ACOD1, derived from the TCA cycle.
2. Itaconate: The product of the ACOD1-catalyzed reaction, which acts as an anti-inflammatory and antimicrobial agent.
3. TCA Cycle Enzymes: Works in concert with other TCA cycle enzymes, indirectly influencing cellular metabolism.
4. Immune Signaling Pathways: Itaconate produced by ACOD1 can interact with and inhibit various signaling pathways involved in inflammation and immune responses, such as NF-κB.

Clinical Significance

Alterations in ACOD1 activity or expression can have significant implications for health and disease:

1. Infectious Diseases: Upregulation of ACOD1 and itaconate production is a critical defense mechanism against various bacterial and fungal infections.
2. Inflammatory Disorders: Dysregulation of ACOD1 can lead to either excessive inflammation or insufficient immune response, contributing to conditions like chronic inflammatory diseases and autoimmune disorders.
3. Cancer: The role of itaconate in modulating metabolic pathways and inflammation suggests that ACOD1 may influence cancer cell metabolism and tumor microenvironment.
4. Metabolic Diseases: ACOD1 activity affects the TCA cycle and overall cellular metabolism, linking it to metabolic diseases where inflammation and immune response play a role.

Summary

Cis-aconitate decarboxylase (ACOD1), also known as immune-responsive gene 1 (IRG1), is an enzyme that converts cis-aconitate to itaconate. Itaconate has potent antimicrobial and anti-inflammatory properties, making ACOD1 a critical player in immune responses and inflammation regulation. ACOD1 influences cellular metabolism, modulates immune signaling pathways, and helps defend against infections. Dysregulation of ACOD1 is associated with various diseases, including infectious diseases, inflammatory disorders, cancer, and metabolic diseases. Understanding the structure, function, and clinical significance of ACOD1 provides valuable insights into its role in health and disease and highlights its potential as a therapeutic target.