Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DETBNY4)

DME Name Porphobilinogen synthase (ALAD)
Synonyms Delta-aminolevulinic acid dehydratase; Porpho-bilinogensynthase; ALAD; ALADH
Gene Name ALAD
UniProt ID
HEM2_HUMAN
INTEDE ID
DME0401
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
210
EC Number EC: 4.2.1.24
Lyases
Carbon-oxygen lyase
Hydro-lyase
EC: 4.2.1.24
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MQPQSVLHSGYFHPLLRAWQTATTTLNASNLIYPIFVTDVPDDIQPITSLPGVARYGVKR
LEEMLRPLVEEGLRCVLIFGVPSRVPKDERGSAADSEESPAIEAIHLLRKTFPNLLVACD
VCLCPYTSHGHCGLLSENGAFRAEESRQRLAEVALAYAKAGCQVVAPSDMMDGRVEAIKE
ALMAHGLGNRVSVMSYSAKFASCFYGPFRDAAKSSPAFGDRRCYQLPPGARGLALRAVDR
DVREGADMLMVKPGMPYLDIVREVKDKHPDLPLAVYHVSGEFAMLWHGAQAGAFDLKAAV
LEAMTAFRRAGADIIITYYTPQLLQWLKEE
Function
This enzyme catalyzes an early step in the biosynthesis of tetrapyrroles. It binds two molecules of 5-aminolevulinate per subunit, each at a distinct site, and catalyzes their condensation to form porphobilinogen.
KEGG Pathway
( )
( )
Reactome Pathway
Neutrophil degranulation (R-HSA-6798695 )
Heme biosynthesis (R-HSA-189451 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
1 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Aminolevulinic acid hci DMS4BLQ Acne vulgaris ED80 Approved [6]

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 2.92E-26 -1.00E+00 -1.36E+00
Alopecia ED70 Skin from scalp 2.76E-07 -3.54E-01 -1.19E+00
Alzheimer's disease 8A20 Entorhinal cortex 2.82E-03 1.43E-01 4.46E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 1.17E-01 2.28E-01 9.18E-01
Aortic stenosis BB70 Calcified aortic valve 2.97E-01 -2.32E-01 -2.95E-01
Apnea 7A40 Hyperplastic tonsil 4.24E-01 1.37E-02 2.64E-02
Arthropathy FA00-FA5Z Peripheral blood 9.33E-01 1.31E-02 7.91E-02
Asthma CA23 Nasal and bronchial airway 1.23E-01 5.37E-02 2.01E-01
Atopic dermatitis EA80 Skin 1.87E-06 -4.10E-01 -1.82E+00
Autism 6A02 Whole blood 3.93E-01 -9.63E-02 -5.27E-01
Autoimmune uveitis 9A96 Peripheral monocyte 1.00E+00 -2.49E-01 -8.23E-01
Autosomal dominant monocytopenia 4B04 Whole blood 6.16E-01 -1.12E-01 -2.58E-01
Bacterial infection of gingival 1C1H Gingival tissue 5.59E-09 -3.79E-01 -1.03E+00
Batten disease 5C56.1 Whole blood 2.23E-01 -8.21E-02 -6.51E-01
Behcet's disease 4A62 Peripheral blood 8.82E-01 -4.61E-02 -2.55E-01
Bipolar disorder 6A60-6A6Z Prefrontal cortex 1.83E-01 5.87E-02 3.51E-01
Bladder cancer 2C94 Bladder tissue 3.22E-07 -8.59E-01 -5.41E+00
Breast cancer 2C60-2C6Z Breast tissue 2.52E-18 -1.97E-01 -5.17E-01
Cardioembolic stroke 8B11.20 Whole blood 2.47E-02 -2.08E-01 -9.67E-01
Cervical cancer 2C77 Cervical tissue 1.57E-03 -3.02E-01 -9.60E-01
Childhood onset rheumatic disease FA20.Z Peripheral blood 4.23E-01 1.03E-01 2.92E-01
Chronic hepatitis C 1E51.1 Whole blood 9.61E-01 4.14E-02 2.23E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 6.38E-01 -1.83E-03 -7.75E-03
Chronic obstructive pulmonary disease CA22 Small airway epithelium 1.34E-03 -1.58E-01 -6.49E-01
Chronic rhinosinusitis CA0A Sinus mucosa tissue 2.93E-01 -1.59E-02 -9.42E-02
Colon cancer 2B90 Colon tissue 1.98E-47 -6.15E-01 -1.83E+00
Coronary artery disease BA80-BA8Z Peripheral blood 1.20E-01 1.33E-01 5.20E-01
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 9.62E-01 1.31E-01 5.87E-01
Endometriosis GA10 Endometrium tissue 6.64E-01 -1.01E-01 -3.01E-01
Familial hypercholesterolemia 5C80.00 Peripheral blood 7.99E-01 2.07E-02 1.62E-01
Familial hypercholesterolemia 5C80.00 Whole blood 6.33E-03 1.75E-01 9.58E-01
Gastric cancer 2B72 Gastric tissue 3.50E-01 -5.63E-01 -8.13E-01
Glioblastopma 2A00.00 Nervous tissue 9.38E-71 -5.50E-01 -1.26E+00
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 3.54E-07 -3.37E-01 -1.15E+01
Glioma 2A00.0Y-2A00.0Z White matter tissue 8.67E-03 -5.75E-01 -9.57E-01
Head and neck cancer 2D42 Head and neck tissue 5.52E-22 -5.03E-01 -1.29E+00
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 1.67E-01 1.13E-01 3.68E-01
Huntington's disease 8A01.10 Whole blood 3.33E-01 -6.44E-02 -4.32E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 2.50E-01 9.05E-02 3.31E-01
Immunodeficiency 4A00-4A20 Peripheral blood 2.39E-01 4.77E-02 5.78E-01
Influenza 1E30 Whole blood 5.11E-01 -3.85E-03 -1.78E-02
Interstitial cystitis GC00.3 Bladder tissue 4.75E-05 -3.74E-01 -5.30E+00
Intracranial aneurysm 8B01.0 Intracranial artery 7.05E-01 8.92E-04 5.95E-03
Irritable bowel syndrome DD91.0 Rectal colon tissue 6.36E-02 -1.04E-01 -3.15E-01
Ischemic stroke 8B11 Peripheral blood 3.15E-01 -9.49E-02 -4.01E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 2.96E-02 -9.48E-02 -4.75E-01
Lateral sclerosis 8B60.4 Skin 7.39E-01 -9.26E-02 -6.29E-01
Lateral sclerosis 8B60.4 Cervical spinal cord 6.58E-01 4.82E-03 2.47E-02
Liver cancer 2C12.0 Liver tissue 3.32E-05 -4.34E-01 -7.33E-01
Liver failure DB99.7-DB99.8 Liver tissue 1.14E-05 -1.22E+00 -3.22E+00
Lung cancer 2C25 Lung tissue 3.52E-05 -1.47E-01 -4.09E-01
Lupus erythematosus 4A40 Whole blood 3.16E-02 -7.24E-02 -2.54E-01
Major depressive disorder 6A70-6A7Z Hippocampus 5.51E-01 8.86E-03 5.11E-02
Major depressive disorder 6A70-6A7Z Whole blood 9.50E-01 -3.10E-02 -9.66E-02
Melanoma 2C30 Skin 1.16E-02 -2.46E-01 -4.32E-01
Multiple myeloma 2A83.1 Peripheral blood 7.24E-01 -7.85E-03 -8.88E-02
Multiple myeloma 2A83.1 Bone marrow 5.61E-07 8.89E-01 5.50E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 3.14E-01 -1.20E-01 -6.69E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 8.73E-04 1.30E-01 5.46E-01
Myelofibrosis 2A20.2 Whole blood 2.31E-02 6.51E-01 4.58E+00
Myocardial infarction BA41-BA50 Peripheral blood 4.15E-01 -2.90E-02 -4.97E-02
Myopathy 8C70.6 Muscle tissue 5.60E-02 -8.16E-02 -9.04E-01
Neonatal sepsis KA60 Whole blood 2.41E-11 4.08E-01 1.71E+00
Neuroectodermal tumour 2A00.11 Brain stem tissue 1.13E-07 -1.35E+00 -4.05E+00
Non-alcoholic fatty liver disease DB92 Liver tissue 1.87E-01 2.41E-01 6.65E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 9.30E-01 -1.08E-01 -4.14E-01
Olive pollen allergy CA08.00 Peripheral blood 9.77E-01 -7.66E-03 -6.18E-02
Oral cancer 2B6E Oral tissue 1.77E-05 -6.14E-01 -9.11E-01
Osteoarthritis FA00-FA0Z Synovial tissue 3.37E-01 1.33E-01 5.04E-01
Osteoporosis FB83.1 Bone marrow 6.18E-01 -3.19E-01 -9.25E-01
Ovarian cancer 2C73 Ovarian tissue 1.26E-01 -1.35E-01 -3.76E-01
Pancreatic cancer 2C10 Pancreas 2.03E-01 3.98E-02 1.02E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 3.06E-02 -2.29E-01 -7.03E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 2.37E-02 1.09E-01 6.40E-01
Pituitary cancer 2D12 Pituitary tissue 4.14E-04 4.39E-01 1.40E+00
Pituitary gonadotrope tumour 2D12 Pituitary tissue 1.98E-03 4.47E-01 1.38E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 3.95E-01 7.02E-02 5.37E-01
Polycythemia vera 2A20.4 Whole blood 1.02E-01 6.28E-02 4.27E-01
Pompe disease 5C51.3 Biceps muscle 8.99E-01 2.24E-02 1.04E-01
Preterm birth KA21.4Z Myometrium 1.40E-01 1.97E-01 5.92E-01
Prostate cancer 2C82 Prostate 6.82E-06 -1.01E+00 -1.60E+00
Psoriasis EA90 Skin 8.65E-08 -1.87E-01 -5.23E-01
Rectal cancer 2B92 Rectal colon tissue 2.34E-04 -4.89E-01 -2.88E+00
Renal cancer 2C90-2C91 Kidney 2.34E-02 -2.34E-01 -3.77E-01
Retinoblastoma 2D02.2 Uvea 1.61E-03 -2.56E-01 -1.55E+00
Rheumatoid arthritis FA20 Synovial tissue 8.24E-04 2.16E-01 9.60E-01
Rhinovirus infection CA42.1 Nasal epithelium tissue 3.74E-01 -1.82E-02 -1.03E-01
Schizophrenia 6A20 Prefrontal cortex 4.03E-01 -3.22E-02 -1.73E-01
Schizophrenia 6A20 Superior temporal cortex 6.91E-01 5.98E-02 3.83E-01
Scleroderma 4A42.Z Whole blood 4.23E-04 -1.68E-01 -1.65E+00
Seizure 8A60-8A6Z Whole blood 1.30E-02 -1.29E-01 -5.90E-01
Sensitive skin EK0Z Skin 7.91E-01 9.60E-02 4.95E-01
Sepsis with septic shock 1G41 Whole blood 2.55E-08 1.05E-01 4.88E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 1.52E-01 4.22E-01 1.47E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 3.24E-01 -6.38E-02 -2.51E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 6.27E-01 2.52E-01 1.18E+00
Sjogren's syndrome 4A43.2 Salivary gland tissue 4.88E-01 3.55E-02 2.28E-01
Skin cancer 2C30-2C3Z Skin 5.10E-52 -7.56E-01 -1.76E+00
Thrombocythemia 3B63 Whole blood 4.18E-01 -5.43E-02 -3.86E-01
Thrombocytopenia 3B64 Whole blood 9.79E-01 2.11E-01 5.58E-01
Thyroid cancer 2D10 Thyroid 2.03E-08 -2.45E-01 -7.10E-01
Tibial muscular dystrophy 8C75 Muscle tissue 3.72E-01 -8.59E-02 -3.43E-01
Tuberous sclerosis complex LD2D.2 Perituberal tissue 3.94E-01 2.81E-01 2.54E+00
Type 2 diabetes 5A11 Liver tissue 3.95E-01 -3.53E-01 -8.34E-01
Ureter cancer 2C92 Urothelium 9.37E-01 5.39E-02 2.77E-01
Uterine cancer 2C78 Endometrium tissue 3.77E-03 -1.15E-01 -2.86E-01
Vitiligo ED63.0 Skin 1.02E-03 2.04E-01 1.97E+00
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⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name Delta-aminolevulinic acid dehydratase (ALAD) DTT Info
DME DTT Type Successful
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Aminolevulinic acid hci DMS4BLQ Acne vulgaris ED80 Approved [1], [2], [3]
1 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Porphobilinogen DM5HMTB N. A. N. A. Phase 2 [4]
10 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
2-Sulfhydryl-Ethanol DMJBO3D Discovery agent N.A. Investigative [4]
3-(2-Aminoethyl)-4-(Aminomethyl)Heptanedioic Acid DMQXPM3 Discovery agent N.A. Investigative [4]
4,7-Dioxosebacic Acid DML5302 Discovery agent N.A. Investigative [4]
4-Oxosebacic Acid DMADSUY Discovery agent N.A. Investigative [4]
5-Fluorolevulinic Acid DMDV48S Discovery agent N.A. Investigative [4]
5-hydroxyvaleric acid DMIXQG6 Discovery agent N.A. Investigative [5]
Delta-Amino Valeric Acid DMV7IAK Discovery agent N.A. Investigative [4]
Formic Acid DMNFZC6 Discovery agent N.A. Investigative [4]
Laevulinic Acid DMTZ17V Discovery agent N.A. Investigative [4]
S,S-(2-Hydroxyethyl)Thiocysteine DMLPAD8 Discovery agent N.A. Investigative [4]
⏷ Show the Full List of 10 Investigative Drug(s)

References

1 Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides. Nat Biotechnol. 2003 May;21(5):566-9.
2 Melatonin protects against delta-aminolevulinic acid-induced oxidative damage in male Syrian hamster Harderian glands. Int J Biochem Cell Biol. 2002 May;34(5):544-53.
3 A novel mutation of delta-aminolaevulinate dehydratase in a healthy child with 12% erythrocyte enzyme activity. Br J Haematol. 1999 Sep;106(4):931-7.
4 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
5 Structure of yeast 5-aminolaevulinic acid dehydratase complexed with the inhibitor 5-hydroxylaevulinic acid. Acta Crystallogr D Biol Crystallogr. 2005 Sep;61(Pt 9):1222-6.
6 Modifying effects of delta-Aminolevulinate dehydratase polymorphism on blood lead levels and ALAD activity. Toxicol Lett. 2018 Oct 1;295:351-356.