AKR1A1
Description
The AKR1A1 (aldo-keto reductase family 1 member A1) is a protein-coding gene located on chromosome 1.
AKR1A1, also known as Alcohol dehydrogenase [NADP+], Aldehyde reductase, or aldo-keto reductase family 1 member A1, is an enzyme encoded by the AKR1A1 gene in humans. It belongs to the aldo-keto reductase (AKR) superfamily. AKR1A1 catalyzes the NADPH-dependent reduction of a variety of aromatic and aliphatic aldehydes to their corresponding alcohols. It also catalyzes the reduction of mevaldate to mevalonic acid and of glyceraldehyde to glycerol. Mutations in the AKR1A1 gene have been linked to non-Hodgkin's lymphoma. The AKR1A1 gene is located on chromosome 1p34.1 and comprises 10 exons. The protein consists of 325 amino acids and has a molecular weight of 36573Da. Its tertiary structure features a beta/alpha-barrel with the coenzyme-binding site positioned at the carboxy-terminus end of the barrel. Alternative splicing of the AKR1A1 gene results in two transcript variants that encode the same protein. AKR1A1 is highly expressed in the kidney and liver, and moderately expressed in the cerebrum, small intestine, and testis. Small amounts of AKR1A1 are present in the lung, prostate, and spleen.
AKR1A1 catalyzes the NADPH-dependent reduction of a wide range of carbonyl-containing compounds to their corresponding alcohols. It exhibits enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides, and bile acids, with a preference for negatively charged substrates like glucuronate and succinic semialdehyde. AKR1A1 acts as a detoxifying enzyme by reducing various toxic aldehydes. It reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic. Additionally, AKR1A1 participates in the detoxification of lipid-derived aldehydes like acrolein. AKR1A1 plays a role in the activation of procarcinogens, such as polycyclic aromatic hydrocarbon trans-dihydrodiols, and in the metabolism of various xenobiotics and drugs, including the anthracyclines doxorubicin (DOX) and daunorubicin (DAUN). Notably, AKR1A1 does not exhibit reductase activity towards retinoids.
AKR1A1 is also known as ALDR1, ALR, ARM, DD3, HEL-S-6.
Associated Diseases
- glycogen storage disease due to lactate dehydrogenase H-subunit deficiency
- Kallmann syndrome
- alcohol sensitivity, acute
- Mazabraud syndrome
- hyperostosis corticalis generalisata
- gnathodiaphyseal dysplasia
- familial avascular necrosis of femoral head
- autosomal dominant osteosclerosis, Worth type
