Aldose reductase

Aldose reductase is an enzyme that belongs to the aldo-keto reductase (AKR) superfamily, which plays a crucial role in the metabolism of glucose to sorbitol. This enzyme is of significant interest in medical research due to its involvement in the development of various diabetes-related complications, such as diabetic neuropathy, diabetic retinopathy, and diabetic nephropathy. Aldose reductase catalyzes the reduction of glucose to sorbitol using NADPH as a cofactor. The accumulation of sorbitol in cells, due to the action of aldose reductase, is believed to be a key factor in the pathogenesis of diabetic complications.

Function

Aldose reductase is primarily found in the liver and kidney, but it is also present in other tissues, including the eyes, nerves, and blood vessels. The enzyme's main function is to catalyze the first step in the polyol pathway, where it reduces aldose sugars to their corresponding alcohols. For example, it reduces glucose to sorbitol, which is then further metabolized to fructose by another enzyme, sorbitol dehydrogenase. This pathway is of minor importance under normal glucose concentrations but becomes highly active under hyperglycemic conditions, leading to various cellular dysfunctions.

Clinical Significance

The role of aldose reductase in diabetic complications has made it a target for therapeutic intervention. Inhibitors of aldose reductase are being studied as potential treatments for preventing or slowing the progression of diabetic complications. These inhibitors work by blocking the conversion of glucose to sorbitol, thereby reducing the accumulation of sorbitol within cells and preventing the associated damage.

Aldose Reductase Inhibitors

Several aldose reductase inhibitors (ARIs) have been identified, including epalrestat and fidarestat. These drugs have shown promise in clinical trials for the treatment of diabetic neuropathy, with improvements in nerve conduction velocity and various symptoms of neuropathy. However, the effectiveness of ARIs in treating other diabetic complications remains under investigation.

Genetics

The gene encoding aldose reductase is located on chromosome 7q35. Mutations in this gene can affect the enzyme's activity, potentially influencing the susceptibility to diabetic complications among individuals with diabetes.

Research Directions

Research on aldose reductase continues to explore its exact role in the development of diabetic complications and the potential for ARIs in clinical practice. Studies are also investigating the genetic factors that may influence the activity of aldose reductase and the response to ARIs.

See Also

• Diabetes mellitus
• Polyol pathway
• Diabetic neuropathy
• Diabetic retinopathy
• Diabetic nephropathy