Target intelligence / Profile preview

Alcohol dehydrogenase [NADP(+)] (AKR1A1) (AKR1A1)

Target
AKR1A1
Molecular classification
Enzyme, Aldo-keto reductase family, Oxidoreductase
01

Overview

Alcohol dehydrogenase [NADP(+)], commonly referred to as aldehyde reductase (AKR1A1), is a key enzyme in the aldo-keto reductase superfamily that is predominantly expressed in the human kidney and liver (UniProt P14550). It facilitates the NADPH-dependent reduction of a wide array of aldehydes, including those produced during lipid peroxidation and the breakdown of biogenic amines, into less reactive alcohols (NCBI Gene 103). In the renal system, AKR1A1 serves a critical protective role by detoxifying reactive carbonyl species and participating in the metabolism of D-glucuronate (PubMed 15647516). While it shares structural homology with aldose reductase (AKR1B1), AKR1A1 is distinct in its substrate specificity and its minimal involvement in the polyol pathway associated with diabetic complications (PubMed 15647516). The enzyme is a known target of inhibition by the anticonvulsant drug valproic acid, which can interfere with the clearance of endogenous aldehydes and affect metabolic homeostasis (PubMed 11483377). Research suggests that altered AKR1A1 activity may contribute to oxidative stress and is observed in certain oncogenic processes, making it a relevant focus for toxicological and therapeutic studies (PubMed 15647516).

Other names
Aldehyde reductaseALR1ALDR1Aldehyde reductase 1Glucuronate reductase
02

Mechanism of action

Inhibition of the NADPH-dependent reduction of aldehydes to alcohols, thereby modulating the levels of reactive carbonyl species and endogenous metabolites.

03

Biological functions

Aldehyde metabolismDetoxificationOxidoreductionGlucuronate metabolism
04

Disease associations

Diabetes mellitusOxidative stressRenal cell carcinomaLiver disease
05

Safety considerations

Potential for drug-drug interactions due to altered metabolism of co-administered drugsAccumulation of toxic reactive aldehydes if inhibitedInterference with the glucuronate pathway
06

Interacting drugs

Valproic acid

3 more in the full profile.

07

Biomarkers

AKR1A1 protein expression levelsUrinary 3-deoxyglucosone levelsRenal AKR1A1 mRNA expression

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