Details of Drug-Metabolizing Enzyme (DME)

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

DME Name Leukotriene B4 omega-hydroxylase (CYP4F3)
Synonyms Leukotriene-B(4) 20-monooxygenase 2; Docosahexaenoic acid omega-hydroxylase CYP4F3; Leukotriene-B(4) omega-hydroxylase 2; Cytochrome P450 4F3; Cytochrome P450-LTB-omega; CYP4F3; CYPIVF3; LTB4H
Gene Name CYP4F3
UniProt ID
CP4F3_HUMAN
INTEDE ID
DME0034
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
4051
EC Number EC: 1.14.14.1
Oxidoreductase
Oxygen paired donor oxidoreductase
Flavin/flavoprotein donor oxidoreductase
EC: 1.14.14.1
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MPQLSLSSLGLWPMAASPWLLLLLVGASWLLARILAWTYTFYDNCCRLRCFPQPPKRNWF
LGHLGLIHSSEEGLLYTQSLACTFGDMCCWWVGPWHAIVRIFHPTYIKPVLFAPAAIVPK
DKVFYSFLKPWLGDGLLLSAGEKWSRHRRMLTPAFHFNILKPYMKIFNESVNIMHAKWQL
LASEGSARLDMFEHISLMTLDSLQKCVFSFDSHCQEKPSEYIAAILELSALVTKRHQQIL
LYIDFLYYLTPDGQRFRRACRLVHDFTDAVIQERRRTLPSQGVDDFLQAKAKSKTLDFID
VLLLSKDEDGKKLSDEDIRAEADTFMFEGHDTTASGLSWVLYHLAKHPEYQERCRQEVQE
LLKDREPKEIEWDDLAQLPFLTMCIKESLRLHPPVPAVSRCCTQDIVLPDGRVIPKGIIC
LISVFGTHHNPAVWPDPEVYDPFRFDPKNIKERSPLAFIPFSAGPRNCIGQAFAMAEMKV
VLGLTLLRFRVLPDHTEPRRKPELVLRAEGGLWLRVEPLS
Function
This enzyme is involved in the metabolism of various endogenous substrates, including fatty acids and their oxygenated derivatives (oxylipins). Isoform CYP4F3A catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of oxylipins in myeloid cells, displaying higher affinity for arachidonate metabolite leukotriene B4 (LTB4) and inactivates LTB4 via three successive oxidative transformations to 20-hydroxy-LTB4, then to 20-oxo-LTB4 and to 20- carboxy-LTB4. It exhibits omega-hydroxylase activity toward long-chain fatty acid epoxides with preference for 8,9-epoxy- (5Z,11Z,14Z)-eicosatrienoate (EET) and 9,10-epoxyoctadecanoate. It contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid, by catalyzing successive omega-oxidations to the corresponding dicarboxylic acid, thereby initiating chain shortening. Isoform CYP4F3B catalyzes predominantly the oxidation of the terminal carbon (omega-oxidation) of polyunsaturated fatty acids (PUFAs) and participates in the conversion of arachidonic acid to 20- hydroxyeicosatetraenoic acid (20-HETE). Besides, it exhibits high omega-hydroxylase activity toward other PUFAs, including eicosatrienoic acid (ETA), eicosapentaenoic acid (EPA) and docosahexaenoic acid. It can also catalyze the oxidation of the penultimate carbon (omega-1 oxidation) of PUFAs with lower efficiency. It contributes to the degradation of saturated very long-chain fatty acids (VLCFAs) such as docosanoic acid and hexacosanoic acid, by catalyzing successive omega-oxidations and to the corresponding dicarboxylic acids, thereby initiating chain shortening.
KEGG Pathway
Arachidonic acid metabolism (hsa00590 )
Metabolic pathways (hsa01100 )
Reactome Pathway
Fatty acids (R-HSA-211935 )
Miscellaneous substrates (R-HSA-211958 )
Synthesis of Leukotrienes (LT) and Eoxins (EX) (R-HSA-2142691 )
Eicosanoids (R-HSA-211979 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
1 Clinical Trial Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
LTB4 DME26RS Human immunodeficiency virus infection 1C62 Phase 2 [1]

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 8.28E-140 -5.59E+00 -5.88E+00
Alopecia ED70 Skin from scalp 3.58E-01 -5.80E-02 -9.07E-02
Alzheimer's disease 8A20 Entorhinal cortex 3.96E-03 2.90E-01 3.71E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 9.42E-01 2.49E-02 3.35E-01
Aortic stenosis BB70 Calcified aortic valve 6.22E-01 -2.87E-02 -4.91E-02
Apnea 7A40 Hyperplastic tonsil 5.25E-01 -7.87E-01 -2.54E+00
Arthropathy FA00-FA5Z Peripheral blood 1.27E-01 2.23E-01 3.60E-01
Asthma CA23 Nasal and bronchial airway 4.65E-05 4.67E-01 3.60E-01
Atopic dermatitis EA80 Skin 2.90E-01 -2.41E-01 -3.46E-01
Autism 6A02 Whole blood 9.41E-02 3.64E-01 5.61E-01
Autoimmune uveitis 9A96 Peripheral monocyte 5.89E-02 2.23E+00 4.62E+00
Autosomal dominant monocytopenia 4B04 Whole blood 1.15E-02 -9.60E-01 -1.78E+00
Bacterial infection of gingival 1C1H Gingival tissue 1.27E-05 -1.70E-01 -3.43E-01
Batten disease 5C56.1 Whole blood 4.83E-01 4.32E-01 9.77E-01
Behcet's disease 4A62 Peripheral blood 5.19E-01 -6.37E-02 -1.41E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 1.85E-01 -3.45E-02 -5.82E-02
Bladder cancer 2C94 Bladder tissue 6.61E-02 -1.19E+00 -1.45E+00
Breast cancer 2C60-2C6Z Breast tissue 3.28E-07 -2.04E-03 -6.60E-03
Cardioembolic stroke 8B11.20 Whole blood 6.36E-05 4.11E-01 8.97E-01
Cervical cancer 2C77 Cervical tissue 6.86E-03 -3.79E-01 -6.78E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 9.20E-01 4.82E-01 1.35E-01
Chronic hepatitis C 1E51.1 Whole blood 4.55E-02 1.67E-01 8.07E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 1.91E-01 2.75E-03 3.69E-03
Chronic obstructive pulmonary disease CA22 Small airway epithelium 1.36E-01 3.56E-01 3.12E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 1.76E-01 -4.02E-01 -6.52E-01
Colon cancer 2B90 Colon tissue 6.10E-22 6.33E-01 1.08E+00
Coronary artery disease BA80-BA8Z Peripheral blood 5.60E-01 3.44E-03 1.78E-02
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 3.90E-01 -4.89E-02 -3.26E-01
Endometriosis GA10 Endometrium tissue 7.05E-01 -2.25E-02 -1.26E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 6.19E-01 -1.23E-02 -2.29E-02
Familial hypercholesterolemia 5C80.00 Whole blood 3.35E-18 -5.59E+00 -2.48E+00
Gastric cancer 2B72 Gastric tissue 2.06E-01 1.01E+00 1.10E+00
Glioblastopma 2A00.00 Nervous tissue 3.97E-08 4.75E-02 6.08E-02
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 8.66E-01 -5.82E-01 -8.85E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 1.76E-01 -2.67E-01 -1.22E-01
Head and neck cancer 2D42 Head and neck tissue 5.89E-28 -2.42E+00 -2.35E+00
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 7.24E-01 1.85E-03 2.60E-03
Huntington's disease 8A01.10 Whole blood 8.50E-01 -9.37E-03 -6.13E-02
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 1.94E-02 -1.35E+00 -1.16E+00
Immunodeficiency 4A00-4A20 Peripheral blood 9.74E-01 1.40E-02 1.22E-01
Influenza 1E30 Whole blood 2.43E-01 -1.77E-01 -1.18E+00
Interstitial cystitis GC00.3 Bladder tissue 1.03E-03 -1.58E+00 -2.88E+00
Intracranial aneurysm 8B01.0 Intracranial artery 4.97E-01 -4.09E-01 -3.45E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 1.04E-01 -7.14E-02 -1.84E-01
Ischemic stroke 8B11 Peripheral blood 1.01E-01 2.94E-01 8.69E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 2.63E-01 5.49E-01 2.43E-01
Lateral sclerosis 8B60.4 Skin 5.01E-01 -4.45E-02 -4.21E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 2.67E-02 2.21E-01 8.88E-01
Liver cancer 2C12.0 Liver tissue 5.54E-32 -9.82E-01 -2.42E+00
Liver failure DB99.7-DB99.8 Liver tissue 4.23E-04 -4.92E+00 -1.75E+01
Lung cancer 2C25 Lung tissue 5.24E-09 -2.11E-01 -2.55E-01
Lupus erythematosus 4A40 Whole blood 1.69E-01 1.50E-01 6.35E-02
Major depressive disorder 6A70-6A7Z Hippocampus 2.09E-01 -6.51E-02 -1.13E-01
Major depressive disorder 6A70-6A7Z Whole blood 8.99E-01 8.44E-02 2.52E-01
Melanoma 2C30 Skin 2.39E-05 -2.12E+00 -1.47E+00
Multiple myeloma 2A83.1 Peripheral blood 8.32E-01 6.51E-02 4.35E-01
Multiple myeloma 2A83.1 Bone marrow 9.21E-01 -1.06E-01 -6.15E-01
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 3.24E-01 -3.69E-01 -6.78E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 8.32E-01 9.35E-03 1.00E-02
Myelofibrosis 2A20.2 Whole blood 4.06E-01 4.58E-02 8.73E-02
Myocardial infarction BA41-BA50 Peripheral blood 9.00E-04 2.46E+00 1.04E+00
Myopathy 8C70.6 Muscle tissue 6.08E-01 3.26E-02 1.62E-01
Neonatal sepsis KA60 Whole blood 5.16E-01 3.26E-01 2.07E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 2.34E-03 -1.38E+00 -1.24E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 3.62E-01 9.69E-02 3.05E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 6.67E-01 5.11E-02 1.73E-01
Olive pollen allergy CA08.00 Peripheral blood 6.02E-01 -4.23E-02 -9.82E-02
Oral cancer 2B6E Oral tissue 4.67E-02 -1.12E+00 -9.40E-01
Osteoarthritis FA00-FA0Z Synovial tissue 3.26E-01 2.84E-02 1.52E-01
Osteoporosis FB83.1 Bone marrow 6.65E-01 1.48E-03 8.08E-03
Ovarian cancer 2C73 Ovarian tissue 4.25E-14 6.63E-01 4.14E+00
Pancreatic cancer 2C10 Pancreas 9.73E-06 1.53E+00 1.67E+00
Parkinson's disease 8A00.0 Substantia nigra tissue 4.12E-01 -7.96E-02 -1.34E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 1.46E-04 1.33E+00 2.48E+00
Pituitary cancer 2D12 Pituitary tissue 3.29E-01 9.23E-02 1.74E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 1.30E-01 2.79E-01 4.43E-01
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 8.07E-01 -3.42E-02 -8.16E-02
Polycythemia vera 2A20.4 Whole blood 2.53E-02 1.32E-01 2.47E-01
Pompe disease 5C51.3 Biceps muscle 3.03E-01 -2.73E-02 -9.23E-02
Preterm birth KA21.4Z Myometrium 1.84E-01 -6.65E-02 -9.78E-02
Prostate cancer 2C82 Prostate 1.03E-01 -3.68E-01 -6.24E-01
Psoriasis EA90 Skin 1.04E-09 4.98E-01 8.29E-01
Rectal cancer 2B92 Rectal colon tissue 2.79E-01 8.81E-02 2.03E-01
Renal cancer 2C90-2C91 Kidney 1.08E-02 -3.54E+00 -1.59E+00
Retinoblastoma 2D02.2 Uvea 4.81E-01 -9.98E-03 -1.13E-01
Rheumatoid arthritis FA20 Synovial tissue 1.55E-01 -3.15E-01 -8.91E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 2.18E-01 -1.38E-01 -3.32E-01
Schizophrenia 6A20 Prefrontal cortex 4.51E-01 3.20E-03 6.11E-03
Schizophrenia 6A20 Superior temporal cortex 2.34E-01 -1.71E-02 -5.75E-02
Scleroderma 4A42.Z Whole blood 5.13E-02 3.76E-01 1.31E+00
Seizure 8A60-8A6Z Whole blood 4.28E-01 2.05E-01 1.81E-01
Sensitive skin EK0Z Skin 5.39E-01 -1.08E-01 -3.39E-01
Sepsis with septic shock 1G41 Whole blood 3.15E-04 6.32E-01 4.84E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 3.48E-01 -4.91E-02 -9.22E-02
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 1.26E-02 1.21E-01 9.62E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 4.80E-01 4.25E-02 3.46E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 1.29E-01 5.63E-03 6.82E-02
Skin cancer 2C30-2C3Z Skin 9.24E-44 -1.23E+00 -1.54E+00
Thrombocythemia 3B63 Whole blood 3.09E-01 -4.01E-02 -7.66E-02
Thrombocytopenia 3B64 Whole blood 2.90E-01 1.07E-01 3.33E-01
Thyroid cancer 2D10 Thyroid 7.47E-01 -1.11E-02 -3.67E-02
Tibial muscular dystrophy 8C75 Muscle tissue 8.67E-02 -5.73E-02 -2.58E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 4.89E-02 1.26E+00 1.51E+01
Type 2 diabetes 5A11 Liver tissue 7.35E-01 5.10E-02 1.21E-01
Ureter cancer 2C92 Urothelium 3.24E-01 -8.81E-02 -9.12E-02
Uterine cancer 2C78 Endometrium tissue 4.55E-06 7.54E-01 5.34E-01
Vitiligo ED63.0 Skin 9.45E-01 -1.85E-01 -4.50E-01
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References

1 Leukotriene B4: metabolism and signal transduction. Arch Biochem Biophys. 2001 Jan 15;385(2):231-41.