aldoketoreduktases

Aldoketoreductases (AKRs) are a superfamily of enzymes that catalyze the reduction of aldehydes and ketones to alcohols. They are primarily involved in the metabolism of various endogenous and exogenous compounds, including steroids, prostaglandins, carbohydrates, and xenobiotics. AKRs belong to the short-chain dehydrogenase/reductase (SDR) enzyme family, characterized by a conserved catalytic triad and a cofactor binding domain.

The general reaction catalyzed by AKRs involves the transfer of a hydride ion from a reduced nicotinamide adenine dinucleotide phosphate (NADPH) or nicotinamide adenine dinucleotide (NADH) cofactor to the carbonyl group of a substrate. This reaction is typically reversible, meaning AKRs can also catalyze the oxidation of alcohols back to aldehydes or ketones.

The AKR superfamily is diverse, with numerous members identified in various organisms, from bacteria to humans. In humans, AKRs play crucial roles in detoxification, biosynthesis, and the regulation of cellular processes. For instance, AKR1B1, also known as aldose reductase, is involved in the metabolism of glucose and is implicated in diabetic complications. AKR1C enzymes are involved in the metabolism of steroid hormones and are targets for the treatment of hormone-dependent cancers.

Dysregulation of AKR activity has been associated with various diseases, including diabetes, cancer, and inflammatory disorders. Therefore, AKRs represent important targets for therapeutic intervention, and research is ongoing to develop selective inhibitors or activators of specific AKR family members for the treatment of these conditions. The study of AKRs contributes to our understanding of metabolic pathways and disease mechanisms.