AKR1A1 Human

Aldo-Keto Reductase Family 1 Member A1 (AKR1A1), also known as aldehyde reductase, is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is ubiquitously expressed in various tissues, including the liver, kidney, and pancreas. AKR1A1 plays a crucial role in the detoxification of aldehydes and ketones, converting them into their corresponding alcohols using NADPH as a cofactor .

The AKR1A1 gene is located on chromosome 1 at the position 1p34.1 and consists of 10 exons . The protein encoded by this gene is a monomeric oxidoreductase that participates in the reduction of a wide range of substrates, including aromatic and aliphatic aldehydes . The enzyme’s structure allows it to catalyze the reduction of mevaldate to mevalonic acid and glyceraldehyde to glycerol .

AKR1A1 is involved in several biological processes, including:

• Detoxification: It catalyzes the NADPH-dependent reduction of aldehydes, which are toxic byproducts of various metabolic processes .
• Lipid Metabolism: AKR1A1 plays a role in lipid metabolism by reducing lipid peroxidation products .
• Antioxidant Defense: The enzyme helps in maintaining cellular redox balance by reducing reactive aldehydes .

Mutations in the AKR1A1 gene have been associated with various diseases, including non-Hodgkin’s lymphoma . Additionally, AKR1A1 has been found to exert a protective function in alcohol-associated liver disease (ALD) by reducing the accumulation of 4-HNE, a toxic aldehyde, and inhibiting p53 activation . This protective role highlights the enzyme’s importance in mitigating oxidative stress and inflammation in the liver.

Human recombinant AKR1A1 is widely used in research to study its role in detoxification and disease. Studies have shown that AKR1A1 expression is upregulated in response to oxidative stress and inflammation, making it a potential therapeutic target for conditions like ALD and cancer .