protein
Aldo-keto reductase family 1 member A1
Gene
AKR1A1
Organism
Homo sapiens(9606)
Length
325 aa
Mass
36,573 Da
Aldo-keto reductase family 1 member A1 (AKR1A1) is a 325-amino acid enzyme that catalyzes NADPH-dependent reduction of carbonyl-containing compounds to their corresponding alcohols (UniProt: P14550). It displays broad substrate specificity toward endogenous metabolites including aldehydes, ketones, monosaccharides, and bile acids, with particular activity toward negatively charged substrates such as glucuronate and succinic semialdehyde. The enzyme also functions in detoxification of toxic aldehydes, including methylglyoxal and lipid-derived species like acrolein.
Beyond detoxification, AKR1A1 plays roles in procarcinogen activation and xenobiotic metabolism, including processing of anthracycline drugs. A distinctive function involves inhibition of protein S-nitrosylation through degradation of S-nitroso-coenzyme A, thereby modulating metabolic reprogramming in renal proximal tubules.
AKR1A1 is upregulated in Alzheimer's disease brain tissue. Analysis of human post-mortem AD brain compared to age-matched controls using TMT-labeled proteomics across four subcellular fractions revealed a mean log2 fold-change of +0.6396 (Chaparral AD proteomics), indicating consistent elevation across fractions. The functional significance of this upregulation in AD pathogenesis remains to be elucidated.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↑ Up in ADP3
+0.969
P2
+0.651
S2
not detected
S3
+0.299
Mean log₂FC across detected fractions: +0.6396 (3 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols (PubMed:10510318, PubMed:30538128). Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosaccharides and bile acids, with a preference for negatively charged substrates, such as glucuronate and succinic semialdehyde (PubMed:10510318, PubMed:30538128). Functions as a detoxifiying enzyme by reducing a range of toxic aldehydes (By similarity). Reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic (By similarity). Involved also in the detoxification of lipid-derived aldehydes like acrolein (By similarity). 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) (PubMed:11306097, PubMed:18276838). Also acts as an inhibitor of protein S-nitrosylation by mediating degradation of S-nitroso-coenzyme A (S-nitroso-CoA), a cofactor required to S-nitrosylate proteins (PubMed:30538128). S-nitroso-CoA reductase activity is involved in reprogramming intermediary metabolism in renal proximal tubules, notably by inhibiting protein S-nitrosylation of isoform 2 of PKM (PKM2) (By similarity). Also acts as a S-nitroso-glutathione reductase by catalyzing the NADPH-dependent reduction of S-nitrosoglutathione (PubMed:31649033). Displays no reductase activity towards retinoids (By similarity)
Sources
Last updated 5/8/2026, 6:35:05 AM
