AKR1E- Aldo-keto reductase family 1 member E | Elisa - Clia - Antibody - Protein

Background:

AKR1E2, or Aldo-keto reductase family 1 member E2, is indeed a member of the Aldo-keto reductase (AKR) superfamily. However, it is not as extensively studied as some other members of the AKR family.AKR1E2, also known as aldo-keto reductase family 1 member E2, is an enzyme that catalyzes the reduction of various aldehydes and ketones using NADPH as a cofactor. Like other members of the AKR superfamily, AKR1E2 likely plays a role in the metabolism of endogenous compounds, such as steroids, prostaglandins, and lipid peroxidation products, as well as xenobiotics (foreign substances) and drugs.While its specific physiological functions and roles in human health and disease are not as well-characterized as some other AKR family members, ongoing research may shed more light on the significance of AKR1E2 in various metabolic pathways and its potential implications in health and disease

Protein Structure:

• Domains: AKR1E enzymes typically have a conserved (α/β)8-barrel structure, characteristic of the AKR superfamily.
• Active Site: The active site includes a conserved catalytic tetrad (Tyr, Lys, His, Asp) that is essential for its reductase activity.
• NADPH Binding Site: These enzymes bind NADPH as a cofactor, which is necessary for their catalytic function.
• Isoforms: AKR1E is a distinct isoform within the AKR1 subfamily, each with specific substrate preferences and functional roles.

Classification and Subtypes:

• Family: Aldo-keto reductase (AKR) superfamily.
• Subfamily: AKR1, encompassing several enzymes with diverse roles in metabolism.
• AKR1E1: This is one of the specific members within the AKR1E subfamily.

Function and Biological Significance:

• Metabolism of Aldehydes and Ketones: AKR1E enzymes catalyze the reduction of a variety of aldehydes and ketones, contributing to the detoxification of reactive carbonyl compounds.
• Steroid Metabolism: These enzymes are involved in the metabolism of steroids, reducing steroid aldehydes and ketones to their corresponding alcohols, thus regulating steroid hormone activity.
• Detoxification: By reducing toxic aldehydes and ketones, AKR1E enzymes play a critical role in cellular protection against oxidative stress and chemical damage.
• Drug Metabolism: AKR1E enzymes can metabolize certain drugs, impacting their efficacy and clearance from the body.

Interactions:

• Cofactors: AKR1E enzymes require NADPH for their reductase activity.
• Substrates: They act on a wide range of aldehydes and ketones, including endogenous compounds like steroids and xenobiotics.
• Protein-Protein Interactions: AKR1E enzymes may interact with other metabolic enzymes, contributing to coordinated metabolic pathways.

Clinical Issues:

• Cancer: Abnormal expression or activity of AKR1E enzymes can be associated with cancer progression and resistance to chemotherapy, as these enzymes may metabolize anticancer drugs.
• Diabetes: Dysregulation of AKR1E activity can impact glucose metabolism and insulin sensitivity, potentially contributing to diabetes and its complications.
• Oxidative Stress: Impairment in AKR1E activity can lead to increased oxidative stress, contributing to various diseases, including neurodegenerative disorders and cardiovascular diseases.
• Drug Resistance: Overexpression of AKR1E enzymes can lead to drug resistance, particularly in cancer, where they metabolize chemotherapeutic agents, reducing their effectiveness.

Summary:

Aldo-keto reductase family 1 member E (AKR1E) enzymes are crucial for the reduction of aldehydes and ketones, playing significant roles in detoxification, steroid metabolism, and drug metabolism. With a conserved (α/β)8-barrel structure and catalytic tetrad, AKR1E enzymes utilize NADPH to catalyze these reactions. They are involved in maintaining cellular homeostasis by protecting against oxidative stress and chemical damage. Clinical implications of AKR1E include associations with cancer progression, diabetes, oxidative stress-related diseases, and drug resistance. Understanding AKR1E's function and regulation can provide insights into therapeutic strategies for these conditions.