AKR1A - Aldo-keto reductase family 1 member A | Elisa - Clia - Antibody - Protein

Background:

Aldo-keto reductase family 1 member A1 (AKR1A1), also known as aldose reductase, is an enzyme that belongs to the aldo-keto reductase superfamily. This enzyme catalyzes the reduction of a variety of aldehydes and ketones, using NADPH as a cofactor, to produce corresponding alcohols.One of the well-known substrates of AKR1A1 is glucose. In particular, AKR1A1 catalyzes the conversion of glucose to sorbitol, which is an intermediate in the polyol pathway. This pathway is implicated in the pathogenesis of diabetic complications, as excessive sorbitol accumulation can lead to cellular damage and dysfunction, particularly in tissues that do not require insulin for glucose uptake, such as the lens of the eye and peripheral nerves. AKR1A1 is expressed in various tissues throughout the body, including the liver, kidney, lens, and peripheral nerves. Its expression and activity are regulated by various factors, including glucose levels and oxidative stress.

Protein Structure:

• Domains: AKR1A1 has a characteristic (α/β)8-barrel structure, typical of the aldo-keto reductase family.
• Active Site: Contains a conserved catalytic tetrad (Tyr, Lys, His, Asp) essential for its enzymatic activity.
• NADP(H) Binding Site: The enzyme binds NADP(H) as a cofactor, which is critical for its reductase activity.
• Isoforms: While AKR1A1 is a specific member of the aldo-keto reductase family, it shares structural and functional similarities with other family members, including variations in isoforms adapted to specific substrates and tissue distributions.

Classification and Subtypes:

• Family: Aldo-keto reductase (AKR) superfamily.
• Subfamily: AKR1, which includes several members with diverse functions in metabolism.
• AKR1A1: Also known as alcohol dehydrogenase (NADP+), it is one specific isoform within the AKR1 subfamily.

Function and Biological Significance:

• Detoxification: AKR1A1 is involved in the reduction of toxic aldehydes and ketones, protecting cells from oxidative stress and damage.
• Drug Metabolism: Plays a role in the metabolism and detoxification of various drugs and xenobiotics.
• Aldehyde Metabolism: Reduces aldehydes derived from lipid peroxidation and other metabolic processes to their corresponding alcohols.
• Carbohydrate Metabolism: Participates in the conversion of glucose to sorbitol, which is important in polyol pathway of glucose metabolism.
• Hormone Metabolism: Involved in the biosynthesis and metabolism of steroids and prostaglandins.

Interactions:

• Cofactors: Interacts with NADP(H), which is required for its reductase activity.
• Substrate Specificity: Binds to a variety of aldehydes and ketones, showcasing broad substrate specificity.
• Other Proteins: May interact with other metabolic enzymes and proteins involved in oxidative stress response.

Clinical Issues:

• Diabetes Complications: AKR1A1 activity in the polyol pathway is implicated in the development of diabetic complications, such as neuropathy and retinopathy.
• Cancer: Aberrant expression and activity of AKR1A1 have been observed in various cancers, where it may influence tumor progression and drug resistance.
• Cardiovascular Diseases: By participating in the metabolism of lipid peroxidation products, AKR1A1 is linked to the pathogenesis of atherosclerosis and other cardiovascular conditions.
• Drug Resistance: Overexpression of AKR1A1 can contribute to resistance to chemotherapy drugs, complicating cancer treatment.

Summary:

Aldo-keto reductase family 1 member A1 (AKR1A1) is a versatile enzyme involved in the reduction of aldehydes and ketones, playing crucial roles in detoxification, drug metabolism, and carbohydrate and hormone metabolism. With a conserved structure typical of the aldo-keto reductase family, AKR1A1 interacts with NADP(H) to carry out its functions. It has significant clinical implications, including roles in diabetic complications, cancer progression, cardiovascular diseases, and drug resistance, making it an important target for therapeutic intervention and clinical research.