Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DED2FW3)

DME Name Aldo-keto reductase 1A1 (AKR1A1)
Synonyms Aldo-keto reductase family 1 member A1; Glucuronate reductase; Glucuronolactone reductase; Alcohol dehydrogenase [NADP(+)]; Aldehyde reductase; AKR1A1; ALDR1; ALR
Gene Name AKR1A1
UniProt ID
AK1A1_HUMAN
INTEDE ID
DME0098
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Gene ID
10327
EC Number EC: 1.1.1.2
Oxidoreductase
CH-OH donor oxidoreductase
NAD/NADP oxidoreductase
EC: 1.1.1.2
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MAASCVLLHTGQKMPLIGLGTWKSEPGQVKAAVKYALSVGYRHIDCAAIYGNEPEIGEAL
KEDVGPGKAVPREELFVTSKLWNTKHHPEDVEPALRKTLADLQLEYLDLYLMHWPYAFER
GDNPFPKNADGTICYDSTHYKETWKALEALVAKGLVQALGLSNFNSRQIDDILSVASVRP
AVLQVECHPYLAQNELIAHCQARGLEVTAYSPLGSSDRAWRDPDEPVLLEEPVVLALAEK
YGRSPAQILLRWQVQRKVICIPKSITPSRILQNIKVFDFTFSPEEMKQLNALNKNWRYIV
PMLTVDGKRVPRDAGHPLYPFNDPY
Function
This enzyme catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. It 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. It functions as a detoxifiying enzyme by reducing a range of toxic aldehydes. It can reduces methylglyoxal and 3-deoxyglucosone, which are present at elevated levels under hyperglycemic conditions and are cytotoxic. It is also involved in the detoxification of lipid-derived aldehydes like acrolein. It 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).
KEGG Pathway
Glycerolipid metabolism (hsa00561 )
Glycolysis / Gluconeogenesis (hsa00010 )
Metabolic pathways (hsa01100 )
Pentose and glucuronate interconversions (hsa00040 )
Reactome Pathway
Glutathione conjugation (R-HSA-156590 )
Formation of xylulose-5-phosphate (R-HSA-5661270 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
3 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Doxorubicin DMVP5YE Acute myelogenous leukaemia 2A41 Approved [1]
Ethanol DMDRQZU Chronic pain MG30 Approved [2]
NADH DM5NM6E Parkinson disease 8A00.0 Approved [3]
4 Investigative Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
2,3-dihydroxypropanal DMOWNB4 Discovery agent N.A. Investigative [4]
BRN-0471734 DMZMWVX N. A. N. A. Investigative [4]
D-glucuronate DM1YBTC N. A. N. A. Investigative [4]
Nitrobenzaldehyde DM4UHB5 N. A. N. A. Investigative [4]
Experimental Enzyme Kinetic Data of Drugs
Drug Name Indication Highest Status Kinetic Data REF
2,3-dihydroxypropanal Discovery agent [N.A.] Investigative Km = 1.7 microM [4]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 5.36E-32 7.19E-01 1.51E+00
Alopecia ED70 Skin from scalp 2.45E-02 2.19E-02 1.16E-01
Alzheimer's disease 8A20 Entorhinal cortex 1.75E-02 -6.85E-02 -2.92E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 4.43E-02 1.80E-01 6.26E-01
Aortic stenosis BB70 Calcified aortic valve 8.53E-01 -3.94E-02 -4.84E-02
Apnea 7A40 Hyperplastic tonsil 1.50E-01 6.71E-01 2.67E+00
Arthropathy FA00-FA5Z Peripheral blood 1.69E-01 -2.86E-01 -1.12E+00
Asthma CA23 Nasal and bronchial airway 4.22E-07 5.51E-01 7.15E-01
Atopic dermatitis EA80 Skin 6.66E-02 2.35E-01 8.70E-01
Autism 6A02 Whole blood 9.83E-02 -4.92E-02 -1.70E-01
Autoimmune uveitis 9A96 Peripheral monocyte 7.44E-01 8.21E-02 4.76E-01
Autosomal dominant monocytopenia 4B04 Whole blood 1.70E-01 5.74E-01 8.25E-01
Bacterial infection of gingival 1C1H Gingival tissue 2.16E-13 3.68E-01 1.27E+00
Batten disease 5C56.1 Whole blood 7.00E-01 -4.42E-03 -3.24E-02
Behcet's disease 4A62 Peripheral blood 7.03E-01 -2.92E-02 -1.63E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 1.63E-01 -2.32E-02 -1.16E-01
Bladder cancer 2C94 Bladder tissue 3.15E-01 -1.54E-01 -7.96E-01
Breast cancer 2C60-2C6Z Breast tissue 6.61E-24 4.61E-01 8.49E-01
Cardioembolic stroke 8B11.20 Whole blood 5.37E-02 -1.21E-01 -6.92E-01
Cervical cancer 2C77 Cervical tissue 3.47E-01 1.73E-01 4.81E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 5.89E-01 3.58E-02 2.75E-02
Chronic hepatitis C 1E51.1 Whole blood 7.09E-01 -1.84E-01 -5.71E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 5.95E-01 -6.42E-03 -1.64E-02
Chronic obstructive pulmonary disease CA22 Small airway epithelium 7.69E-01 9.56E-02 3.33E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 7.42E-01 -5.53E-02 -9.65E-02
Colon cancer 2B90 Colon tissue 1.33E-02 -2.97E-02 -1.13E-01
Coronary artery disease BA80-BA8Z Peripheral blood 9.51E-02 4.20E-01 1.04E+00
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 8.69E-01 1.19E-01 3.16E-01
Endometriosis GA10 Endometrium tissue 3.36E-03 -1.71E-01 -6.47E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 1.12E-01 5.04E-02 3.74E-01
Familial hypercholesterolemia 5C80.00 Whole blood 1.93E-16 1.30E+00 2.10E+00
Gastric cancer 2B72 Gastric tissue 7.14E-01 1.21E-01 9.53E-02
Glioblastopma 2A00.00 Nervous tissue 4.78E-86 4.67E-01 1.32E+00
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 7.54E-01 2.13E-01 4.29E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 1.61E-02 1.33E+00 1.41E+00
Head and neck cancer 2D42 Head and neck tissue 7.60E-36 -7.96E-01 -2.41E+00
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 9.18E-01 -4.78E-02 -1.61E-01
Huntington's disease 8A01.10 Whole blood 8.02E-01 -5.85E-02 -1.45E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 7.90E-02 5.16E-01 1.16E+00
Immunodeficiency 4A00-4A20 Peripheral blood 2.47E-02 1.28E-01 8.32E-01
Influenza 1E30 Whole blood 1.24E-02 -7.31E-01 -2.82E+00
Interstitial cystitis GC00.3 Bladder tissue 1.34E-01 2.02E-01 1.40E+00
Intracranial aneurysm 8B01.0 Intracranial artery 1.25E-05 7.36E-01 3.21E+00
Irritable bowel syndrome DD91.0 Rectal colon tissue 7.51E-02 -7.93E-01 -1.17E+00
Ischemic stroke 8B11 Peripheral blood 2.12E-01 -8.39E-03 -2.93E-02
Juvenile idiopathic arthritis FA24 Peripheral blood 1.58E-14 -8.49E-01 -1.52E+00
Lateral sclerosis 8B60.4 Skin 3.60E-02 1.69E-01 2.33E+00
Lateral sclerosis 8B60.4 Cervical spinal cord 4.48E-01 -2.80E-01 -4.40E-01
Liver cancer 2C12.0 Liver tissue 3.04E-12 -3.93E-01 -1.16E+00
Liver failure DB99.7-DB99.8 Liver tissue 3.73E-02 -2.35E-01 -7.95E-01
Lung cancer 2C25 Lung tissue 1.21E-27 3.56E-01 1.12E+00
Lupus erythematosus 4A40 Whole blood 4.74E-04 6.42E-01 8.24E-01
Major depressive disorder 6A70-6A7Z Hippocampus 4.93E-01 4.95E-03 2.65E-02
Major depressive disorder 6A70-6A7Z Whole blood 3.28E-01 -2.14E-01 -3.01E-01
Melanoma 2C30 Skin 2.96E-02 -3.06E-01 -4.75E-01
Multiple myeloma 2A83.1 Peripheral blood 5.89E-01 -3.92E-02 -6.18E-02
Multiple myeloma 2A83.1 Bone marrow 8.19E-03 4.03E-01 1.42E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 1.71E-01 -8.92E-02 -3.17E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 2.10E-01 6.09E-02 1.78E-01
Myelofibrosis 2A20.2 Whole blood 3.04E-01 -5.75E-02 -2.55E-01
Myocardial infarction BA41-BA50 Peripheral blood 6.17E-02 -5.33E-01 -7.55E-01
Myopathy 8C70.6 Muscle tissue 1.71E-07 1.03E+00 4.23E+00
Neonatal sepsis KA60 Whole blood 2.99E-01 -4.01E-02 -1.33E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 1.24E-06 1.03E+00 3.15E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 1.21E-01 1.22E-01 6.71E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 5.06E-01 1.61E-01 4.77E-01
Olive pollen allergy CA08.00 Peripheral blood 3.41E-01 5.92E-01 8.90E-01
Oral cancer 2B6E Oral tissue 3.06E-01 -1.60E-01 -2.86E-01
Osteoarthritis FA00-FA0Z Synovial tissue 8.66E-02 4.34E-01 6.38E-01
Osteoporosis FB83.1 Bone marrow 8.98E-03 -4.84E-01 -2.31E+00
Ovarian cancer 2C73 Ovarian tissue 8.27E-06 8.91E-01 3.14E+00
Pancreatic cancer 2C10 Pancreas 3.37E-03 2.06E-01 6.87E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 9.18E-01 -8.37E-02 -2.35E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 6.47E-02 1.13E-01 4.76E-01
Pituitary cancer 2D12 Pituitary tissue 1.20E-01 -2.16E-01 -6.52E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 2.50E-02 -4.79E-01 -1.70E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 6.00E-01 -2.42E-02 -1.63E-01
Polycythemia vera 2A20.4 Whole blood 1.12E-01 -1.03E-01 -4.32E-01
Pompe disease 5C51.3 Biceps muscle 3.39E-05 6.91E-01 2.26E+00
Preterm birth KA21.4Z Myometrium 2.13E-01 -2.11E-01 -2.37E+00
Prostate cancer 2C82 Prostate 5.28E-02 4.50E-01 8.03E-01
Psoriasis EA90 Skin 8.45E-01 4.19E-02 1.29E-01
Rectal cancer 2B92 Rectal colon tissue 4.03E-02 -1.65E-01 -8.88E-01
Renal cancer 2C90-2C91 Kidney 3.41E-01 -4.19E-01 -4.55E-01
Retinoblastoma 2D02.2 Uvea 3.81E-06 8.98E-01 3.96E+00
Rheumatoid arthritis FA20 Synovial tissue 6.44E-03 9.22E-01 1.33E+00
Rhinovirus infection CA42.1 Nasal epithelium tissue 1.64E-01 -1.23E-02 -7.17E-02
Schizophrenia 6A20 Prefrontal cortex 9.44E-01 -3.18E-02 -5.94E-02
Schizophrenia 6A20 Superior temporal cortex 6.19E-01 -2.58E-03 -1.09E-02
Scleroderma 4A42.Z Whole blood 3.86E-04 3.26E-01 1.85E+00
Seizure 8A60-8A6Z Whole blood 7.09E-01 2.61E-01 8.13E-01
Sensitive skin EK0Z Skin 3.88E-01 -1.38E-01 -6.98E-01
Sepsis with septic shock 1G41 Whole blood 1.56E-06 -2.10E-01 -5.75E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 9.03E-04 -5.66E-01 -2.12E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 5.33E-03 -6.31E-01 -1.08E+00
Simpson golabi behmel syndrome LD2C Adipose tissue 5.24E-01 -9.25E-02 -4.88E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 7.37E-01 1.25E-01 3.90E-01
Skin cancer 2C30-2C3Z Skin 3.42E-05 -8.20E-02 -1.95E-01
Thrombocythemia 3B63 Whole blood 4.02E-01 -1.72E-01 -7.58E-01
Thrombocytopenia 3B64 Whole blood 4.36E-01 1.76E-01 1.29E-01
Thyroid cancer 2D10 Thyroid 6.12E-01 -5.97E-03 -2.75E-02
Tibial muscular dystrophy 8C75 Muscle tissue 3.82E-03 7.83E-01 1.29E+00
Tuberous sclerosis complex LD2D.2 Perituberal tissue 5.13E-01 -2.73E-01 -1.63E+00
Type 2 diabetes 5A11 Liver tissue 3.62E-01 2.50E-01 1.01E+00
Ureter cancer 2C92 Urothelium 4.71E-01 -4.73E-01 -6.93E-01
Uterine cancer 2C78 Endometrium tissue 1.25E-01 -2.22E-02 -3.85E-02
Vitiligo ED63.0 Skin 7.17E-01 -8.22E-03 -4.11E-02
------------------------------------------------------------------------------------
⏷ Show the Full List of DME Expression Under 107 Diseases

References

1 Carbonyl reductase 1 is a predominant doxorubicin reductase in the human liver. Drug Metab Dispos. 2008 Oct;36(10):2113-20.
2 Functional assessment of human alcohol dehydrogenase family in ethanol metabolism: significance of first-pass metabolism. Alcohol Clin Exp Res. 2006 Jul;30(7):1132-42.
3 Conformational changes and catalysis by alcohol dehydrogenase. Arch Biochem Biophys. 2010 Jan 1;493(1):3-12.
4 The C-terminal loop of aldehyde reductase determines the substrate and inhibitor specificity. Biochemistry. 1996 Nov 12;35(45):14276-80.