Aldo-keto reductase

1. Aldo-keto reductase

Aldo-keto reductases (AKRs) are a superfamily of enzymes that catalyze the reduction of aldehydes and ketones to their corresponding alcohols. These enzymes play crucial roles in the metabolism of sugars, steroids, and other compounds, and are involved in detoxification processes.

Structure and Function

Aldo-keto reductases are characterized by their ability to utilize NADPH as a cofactor to reduce carbonyl groups. The AKR superfamily is defined by a conserved protein fold, which consists of an eight-stranded β/α-barrel. This structure is crucial for the binding of substrates and the catalytic activity of the enzyme.

AKRs are involved in a wide range of biological processes, including the metabolism of glucose, the detoxification of reactive aldehydes, and the biosynthesis of steroids. They are also implicated in the development of certain diseases, such as diabetes and cancer, due to their role in metabolic pathways.

Classification

The AKR superfamily is divided into several families based on sequence similarity and functional characteristics. Some of the well-known families include:

• **AKR1**: Involved in the reduction of aldehydes and ketones in the metabolism of sugars and steroids.
• **AKR2**: Known for their role in the detoxification of reactive aldehydes.
• **AKR3**: Participate in the reduction of xenobiotic compounds.

Biological Significance

Aldo-keto reductases are essential for maintaining cellular homeostasis. They help in the detoxification of harmful aldehydes produced during oxidative stress and lipid peroxidation. By converting these reactive aldehydes into less toxic alcohols, AKRs protect cells from damage.

In addition, AKRs are involved in the regulation of hormone levels. For example, they participate in the conversion of active steroids to their inactive forms, thus modulating hormonal activity.

Clinical Implications

Due to their involvement in critical metabolic pathways, AKRs are potential targets for drug development. Inhibitors of specific AKRs are being investigated for the treatment of diseases such as cancer, where they may help to modulate the metabolism of cancer cells.

Research and Developments

Recent studies have focused on the role of AKRs in drug resistance, particularly in cancer therapy. Understanding the mechanisms by which AKRs contribute to drug metabolism and resistance can lead to the development of more effective therapeutic strategies.

Also see

• Enzyme
• Metabolism
• NADPH
• Oxidative stress
• Steroidogenesis