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protein

Aldo-keto reductase family 1 member A1

AKR1A1
protein:P14550disease:adad:direction:up

Gene

AKR1A1

Organism

Homo sapiens(9606)

Length

325 aa

Mass

36,573 Da

AI summarysource-grounded · cited inline
claude-haiku-4-5-20251001

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 AD

P3

+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.

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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