Aldo-keto reductase

A family of enzymes involved in the reduction of aldehydes and ketones

Aldo-keto reductase (AKR) is a family of enzymes that catalyze the reduction of aldehydes and ketones to their corresponding alcohols. These enzymes play a crucial role in the metabolism of various endogenous and exogenous compounds, including steroids, prostaglandins, and xenobiotics.

Structure

Aldo-keto reductases are characterized by their ability to bind NADPH as a cofactor, which provides the reducing equivalents necessary for the conversion of aldehydes and ketones to alcohols. The structure of AKRs typically includes a conserved beta-alpha-beta fold that forms the core of the enzyme, allowing for the binding of substrates and cofactors.

Function

AKRs are involved in a wide range of biological processes. They are essential in the detoxification of reactive aldehydes and ketones, which can be harmful to cells. By converting these reactive species into less reactive alcohols, AKRs help to protect cells from oxidative stress and damage.

Metabolic Pathways

AKRs participate in several metabolic pathways, including:

• Polyol pathway: In this pathway, aldose reductase, a member of the AKR family, reduces glucose to sorbitol, which is then converted to fructose by sorbitol dehydrogenase.
• Steroid metabolism: AKRs are involved in the reduction of steroid hormones, affecting their activity and metabolism.
• Prostaglandin metabolism: AKRs reduce prostaglandins, modulating their biological activity.

Clinical Significance

Alterations in AKR activity have been associated with various diseases. For example, increased activity of aldose reductase is linked to complications in diabetes mellitus, such as diabetic neuropathy and diabetic retinopathy. Inhibitors of aldose reductase are being investigated as potential therapeutic agents for these conditions.

Related pages

• Aldose reductase
• NADPH
• Polyol pathway
• Steroid metabolism

Gallery

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