Aldo-keto reductase family 1, member A1

Content sourced from Wikipedia, licensed under CC BY-SA 3.0.

Aldo-keto reductase family 1 member A1 (AKR1A1) is a human enzyme that helps detoxify harmful chemicals. It uses the cofactor NADPH to reduce a wide range of aldehydes and ketones into their corresponding alcohols. It also converts mevaldate to mevalonic acid and glyceraldehyde to glycerol.

Gene and structure:
- The AKR1A1 gene is on chromosome 1p34.1 and has 10 exons.
- The protein is 325 amino acids long, about 36.6 kDa.
- It has a beta/alpha-barrel structure with the coenzyme-binding site at the C-terminus.
- There are two transcript variants, but they encode the same protein.

Where it’s found:
- Very high in kidney and liver.
- Moderate in cerebrum, small intestine, and testis.
- Small amounts in lung, prostate, and spleen.
- Not detected in heart or skeletal muscle.

What it does:
- AKR1A1 is a soluble, NADPH-dependent enzyme that reduces many aldehydes and ketones to alcohols.
- It helps detoxify reactive products like 4-hydroxynonenal and contributes to protection against oxidative stress.
- It can participate in the metabolism of certain drugs and carcinogens, including activation of some procarcinogens and processing of daunorubicin and doxorubicin.

Clinical notes:
- A variation in intron 5 has been linked to an increased risk of non-Hodgkin’s lymphoma.
- Genetic variants can have reduced activity and may influence the cardiotoxicity risk of daunorubicin or the metabolism of doxorubicin.