Aldo-keto reductase

Aldo-keto reductase

Structure of aldose reductase, a member of the aldo-keto reductase family.

Aldo-keto reductases (AKRs) are a superfamily of enzymes that catalyze the reduction of aldehydes and ketones to their corresponding alcohols. These enzymes are involved in the metabolism of a wide variety of substrates, including sugars, steroids, and xenobiotics. The AKR superfamily is characterized by its ability to utilize NADPH as a cofactor for the reduction reactions.

Structure

Aldo-keto reductases typically have a conserved beta-alpha-beta fold, which is a common structural motif in many enzymes. The active site of AKRs is usually located in a deep pocket within the enzyme, allowing for specific interactions with the substrate. The structure of aldose reductase, a well-studied member of the AKR family, has been elucidated through X-ray crystallography, revealing important details about its catalytic mechanism.

Function

The primary function of aldo-keto reductases is to catalyze the reduction of carbonyl groups in aldehydes and ketones. This reaction is important in various metabolic pathways, including the polyol pathway, where aldose reductase reduces glucose to sorbitol. AKRs also play a role in the detoxification of reactive aldehydes and the metabolism of steroids and prostaglandins.

Clinical significance

Aldo-keto reductases are implicated in several diseases and pathological conditions. For example, aldose reductase is involved in the development of diabetic complications, such as diabetic retinopathy and neuropathy, due to its role in the polyol pathway. Inhibitors of aldose reductase are being investigated as potential therapeutic agents for these conditions.

Related pages

• Enzyme
• NADPH
• Polyol pathway
• Diabetic retinopathy