AKR7 - Aflatoxin B1 aldehyde reductase member | Elisa - Clia - Antibody - Protein

Background:

Aflatoxin B1 aldehyde reductase, a member of the aldo-keto reductase family 7 (AKR7), is an enzyme that plays a significant role in the detoxification of aflatoxin B1 (AFB1), a potent carcinogenic compound produced by certain molds. The AKR7 family is involved in the reduction of various aldehydes and ketones to their corresponding alcohols, aiding in detoxification processes. This enzyme is involved in the detoxification of aflatoxin B1, a potent carcinogenic compound produced by certain molds, particularly Aspergillus species, which can contaminate food crops such as grains, nuts, and legumes. Aflatoxin B1 is metabolically activated in the liver to form a reactive intermediate called aflatoxin B1-8,9-exo-epoxide, which can bind to DNA and proteins, leading to DNA damage and potentially causing mutations that contribute to the development of liver cancer. AKR7A2 plays a crucial role in the detoxification process by catalyzing the reduction of aflatoxin B1-8,9-exo-epoxide to a less toxic and less reactive form, thereby reducing its potential to cause DNA damage and carcinogenesis.

Protein Structure:

• Domains: AKR7 enzymes exhibit the characteristic (α/β)8-barrel structure of the aldo-keto reductase superfamily.
• Active Site: The active site contains a conserved catalytic tetrad (Tyr, Lys, His, Asp), essential for its reductase activity.
• NADPH Binding Site: These enzymes bind NADPH as a cofactor, which is necessary for their catalytic function.
• Isoforms: There are multiple isoforms within the AKR7 family, each with specific substrate preferences and functional roles.

Classification and Subtypes:

• Family: Aldo-keto reductase (AKR) superfamily.
• Subfamily: AKR7, encompassing enzymes with roles in detoxification of aldehydes and ketones, particularly aflatoxin B1.
• Members: Key members include AKR7A2 (aflatoxin B1 aldehyde reductase) and other isoforms involved in similar detoxification processes.

Function and Biological Significance:

• Detoxification of Aflatoxin B1: AKR7 enzymes are critical in detoxifying aflatoxin B1 by reducing its reactive aldehyde form to less harmful alcohol derivatives, thus preventing its carcinogenic effects.
• Metabolism of Aldehydes and Ketones: Beyond aflatoxin B1, AKR7 enzymes metabolize a variety of toxic aldehydes and ketones, contributing to the protection against oxidative stress and chemical damage.
• Cellular Protection: By reducing toxic compounds, these enzymes play a crucial role in maintaining cellular homeostasis and protecting tissues from damage.

Interactions:

• Cofactors: AKR7 enzymes require NADPH for their reductase activity.
• Substrates: They act on a wide range of aldehydes and ketones, including aflatoxin B1 and other endogenous and exogenous toxic compounds.
• Protein-Protein Interactions: AKR7 enzymes may interact with other metabolic enzymes, contributing to coordinated detoxification pathways.

Clinical Issues:

• Cancer: Inadequate detoxification of aflatoxin B1 by AKR7 enzymes can lead to liver cancer due to the accumulation of this potent carcinogen. Polymorphisms in the AKR7A2 gene might affect individual susceptibility to aflatoxin B1-induced carcinogenesis.
• Liver Disease: AKR7 enzymes are crucial in protecting the liver from aflatoxin B1 and other toxic compounds. Deficiency or impaired function can contribute to liver diseases, including cirrhosis and hepatocellular carcinoma.
• Oxidative Stress: Impairment in AKR7 activity can lead to increased oxidative stress, contributing to various diseases, including neurodegenerative disorders and cardiovascular diseases.
• Drug Metabolism: AKR7 enzymes can influence the metabolism of certain drugs, impacting their efficacy and clearance from the body.

Summary:

Aldo-keto reductase family 7 (AKR7), particularly aflatoxin B1 aldehyde reductase, is essential for the detoxification of aflatoxin B1, a potent carcinogen. With a conserved (α/β)8-barrel structure and catalytic tetrad, AKR7 enzymes utilize NADPH to reduce aldehydes and ketones, protecting cells from oxidative stress and chemical damage. The AKR7 family's role in detoxifying aflatoxin B1 is crucial for preventing liver cancer and other liver diseases. Understanding the function and regulation of AKR7 enzymes can provide insights into therapeutic strategies for conditions associated with exposure to aflatoxins and other toxic compounds.