COMT

CATECHOL-O-METHYLTRANSFERASE

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DESCRIPTION

Catechol-O-methyltransferase catalyzes the transfer of a methyl group from S-adenosylmethionine to catecholamines, including the neurotransmitters dopamine, epinephrine, and norepinephrine. This O-methylation results in one of the major degradative pathways of the catecholamine transmitters. In addition to its role in the metabolism of endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of hypertension, asthma, and Parkinson disease. COMT is found in two forms in tissues, a soluble form (S-COMT) and a membrane-bound form (MB-COMT). The differences between S-COMT and MB-COMT reside within the N-termini. Several transcript variants are formed through the use of alternative translation initiation sites and promoters. Catechol-O methyltransferase is the major pathway for eliminating excess catecholamine neurotransmitters (such as epinephrine or dopamine).

MB-COMT, found in abundance in prefrontal cortex, hippocampus and stratum, is generated preferentially from the human COMT mRNA and the mutant COMT generates less. S-COMT is active metabolically. Evolutionarily, S-COMT is less abundant but more enzymatically active...Catechol-O-methyltransferase (COMT) (Axelrod and Tomchick, 1958) methylates catechol structures, including dopamine (DA), norepinephrine (NE), epinephrine, caffeine, and catechol estrogens. In humans and rodents, COMT is abundantly expressed in pyramidal neurons of the prefrontal cortex (PFC) and hippocampus (Matsumoto et al., 2003) and plays a specific role in the catabolism of cortical DA but not cortical NE (Gogos et al., 1998; Tunbridge et al., 2004; Yavich et al., 2007), likely because of the scarcity of cortical DA transporters (Sesack et al., 1998) and the abundance of cortical NE transporters (Morón et al., 2002). DA signaling in the PFC is critical for modulating higher-order cognitive functions, impacting many domains of human behavior, thought, and emotion (Goldman-Rakic, 1998). Moreover, in humans as well as in monkeys, rats, and mice, cortical DA signaling affects cognitive performance through a U-shaped relationship, with too little or too much DA having deleterious effects (Mattay et al., 2003; Vijayraghavan et al., 2007).(1)

In addition to its role in the metabolism of endogenous substances, COMT is important in the metabolism of catechol drugs used in the treatment of hypertension, asthma, and Parkinson disease. Any compound having a catechol structure, like catechol-estrogens and catechol-containing flavinoids are metabolised by this enzyme and plays a role in the risk of cancer(4).

Catechol-O-methyltransferase is involved in the inactivation of the catecholamine neurotransmitters (dopamine, epinephrine, and norepinephrine). The enzyme introduces a methyl group to the catecholamine, which is donated by S-adenosyl methionine (SAM). Any compound having a catechol structure, like catechol-estrogens and catechol-containing flavonoids, are substrates of COMT and plays a role in the risk of cancer with defects in the conversion of 2-, 4- and 16OH-E1 (hydroxyestrone E1) and E2 (estradiol), especially 4-OH-E1(4).

COMT gene is associated with several variants. The best-studied is Val158Met. Others are rs737865 and rs165599 that have been studied  for association with personality traits.

Val158Met polymorphism: A functional single-nucleotide polymorphism (a common normal variant) of the gene for catechol-O-methyltransferase results in a valine tomethionine mutation at position 158 (Val158Met) rs4680. The Val variant catabolizes dopamine at up to four times the rate of its methionine counterpart. The gene variant has been shown to affect cognitive tasks broadly related to executive function, such as set shifting, response inhibition, abstract thought, and the acquisition of rules or task structure. Furthermore, the polymorphism has been shown to affect ratings of subjective well-being. The Val158Met variant has also been found to influence the effect of aspirin and vitamin E on cardiovascular risk. For COMT rs4680 met allele homozygotes, exclusive allocation to aspirin or vitamin E compared with placebo resulted in age-adjusted lower rates of incident CVD of 40% (95%CI=‐7% to -61%, p=0.023) and 47% (95%CI=-16% to -68%, p=0.006), respectively (Table 4). In contrast, val allele homozygotes had higher CVD rates of 85% (95%CI=5% to 325%, p=0.033) and 50% (95% CI=-17% to 170%, p=0.18), respectively, although only the aspirin allocation increase was significant. Among heterozygotes, allocation to either aspirin or vitamin E did not affect the incidence rate. For met allele homozygotes allocated to both aspirin and vitamin E, the difference in rates compared to those allocated to placebo was not significant, implying a further interaction for allocation to both agents compared with either alone. This further interaction was significant (p=0.006). (5)

Main variants are:

  • rs4680 - COMT V158M (Risk Allele: A) - in linkage disequilibrium with rs4633
  • rs4633 - COMT H62H (Risk Allele: T)
  • rs769224 - COMT P199P (Risk Allele: A)

The VDR FOKI mutation decreases dopamine formation via lack of affect on dopamine receptor D1(6).
 

References:

  1. Papaleo F, Crawley JN, Song J, Lipska BK, Pickel J, Weinberger DR, Chen J. Genetic dissection of the role of catechol-O-methyltransferase in cognition and
    stress reactivity in mice. J Neurosci. 2008 Aug 27;28(35):8709-23. doi: 10.1523/JNEUROSCI.2077-08.2008. PubMed PMID: 18753372; PubMed Central PMCID: PMC2561993.
  2. Blair C, Sulik M, Willoughby M, Mills-Koonce R, Petrill S, Bartlett C, Greenberg M; Family Life Project Investigators. Catechol-O-methyltransferase Val158met polymorphism interacts with early experience to predict executive functions in early childhood. Dev Psychobiol. 2015 Nov;57(7):833-41. doi:10.1002/dev.21332. [PubMed PMID: 26251232].
  3. van Goozen SH, Langley K, Northover C, Hubble K, Rubia K, Schepman K, O'Donovan MC, Thapar A. Identifying mechanisms that underlie links between COMT genotype and aggression in male adolescents with ADHD. J Child Psychol Psychiatry. 2016 Apr;57(4):472-80. doi: 10.1111/jcpp.12464. [PMID: 26395975].
    Jin J, Liu L, Gao Q, Chan RC, Li H, Chen Y, Wang Y, Qian Q. The divergent impact of COMT Val158Met on executive function in children with and without attention-deficit/hyperactivity disorder. Genes Brain Behav. 2016 Feb;15(2):271-9. doi: 10.1111/gbb.12270. [PMID: 26560848].
  4. Cavalieri EL, Stack DE, Devanesan PD, Todorovic R, Dwivedy I, Higginbotham S, Johansson SL, Patil KD, Gross ML, Gooden JK, Ramanathan R, Cerny RL, Rogan EG. Molecular origin of cancer: catechol estrogen-3,4-quinones as endogenous tumor initiators. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10937-42. PubMed [PMID:9380738].
  5. Hall KT, Nelson CP, Davis RB, et. Al. Polymorphisms in catechol-O-methyltransferase modify treatment effects of aspirin on risk of cardiovascular disease. Arterioscler Thromb Vasc Biol. 2014 Sep;34(9):2160-7. doi: 10.1161/ATVBAHA.114.303845. Epub 2014 Jul 17. [PMID: 25035343] [PMCID: PMC4148908].
  6. Ahmadi S, Mirzaei K, Hossein-Nezhad A, Shariati G. Vitamin D receptor FokI genotype may modify the susceptibility to schizophrenia and bipolar mood disorder by regulation of dopamine D1 receptor gene expression. Minerva Med. 2012 Oct;103(5):383-91. [PMID: 23042374].

  

 

AGENTS ASSOCIATED WITH EXPRESSION OF COMT
AGENT EVIDENCE ACTION PUBMED
ACUTE PSYCHOLOGICAL STRESS
ACUTE PSYCHOLOGICAL STRESS
3 UNDEFINED 1
CAFFEIC ACID
CAFFEIC ACID
1 ANTAGONIST 1
CALORIC RESTRICTION
CALORIC RESTRICTION
2 ANTAGONIST 1
CANNABIS SATIVA
CANNABIS SATIVA
3 ANTAGONIST 1
CHLOROGENIC ACID
CHLOROGENIC ACID
1 ANTAGONIST 1
COFFEE
COFFEE
1 ANTAGONIST 1
DIHYDROMYRICETIN
DIHYDROMYRICETIN
1 ANTAGONIST 1
ENVIRONMENTAL NOISE
ENVIRONMENTAL NOISE
2 UNDEFINED 1
EPIGALLOCATECHIN GALLATE (EGCG)
EPIGALLOCATECHIN GALLATE (EGCG)
3 ANTAGONIST 1,2,3
FLUORIDE
FLUORIDE
3 UNDEFINED 1
FOLATE-RICH DIET
FOLATE-RICH DIET
3 AGONIST 1
MAGNESIUM
MAGNESIUM
7 AGONIST 1,2,3
MULTIVITAMIN
MULTIVITAMIN
3 AGONIST 1
MYRICA
MYRICA
1 ANTAGONIST 1
MYRICETIN
MYRICETIN
1 ANTAGONIST 1
MYRICITRIN
MYRICITRIN
1 ANTAGONIST 1
PYRIDOXAL 5' PHOSPHATE
PYRIDOXAL 5' PHOSPHATE
6 AGONIST 1,2
S-ADENYL METHIONINE (SAME)
S-ADENYL METHIONINE (SAME)
1 AGONIST 1
YOKUKANSAN
YOKUKANSAN
2 ANTAGONIST 1
DISEASE ASSOCIATIONS WITH COMT
SNPS ASSOCIATED WITH COMT
REFERENCE ID MAGNITUDE ALLELE KEY CONCEPTS
rs737866 1 C
rs5993882 2 G PAIN, CHRONIC FATIGUE
rs769224 6 A CATECHOLAMINES DEGRADATION
rs4633 8 T RS4680 PAIN SENSITIVITY, PARANOID SCHIZOPHRENIA, HYPERACTIVITY, CHRONIC FATIGUE SYNDROME, ENDOMETRIAL CANCER
rs165631 6 T PROTECTION AGAINST BREAST CANCER WITH BRCA
rs4818 7 A HYPERACTIVITY FIBROMYALGIA PAIN, REDUCED CVD RISK WITH ASPIRIN AND VITAMIN E
rs165722 3 T CANCER TREATMENT, OPIOIDS, MONOAMINE, CANCER
rs165774 6 A HIGH EPINEPHRINE VARIANT, BUT CATALYTICALLY ACTIVE TO DOPAMINE AND NOREPINEPHRINE DEGRADATION
rs4680 8 A DOPAMINE, STRESS, ESTROGEN BLOOD METABOLITES, BREAST CANCER, PAIN, MEMORY, ATTENTION, WARRIOR VS WORRIER, NICOTINE RESPONSE, PAIN SENSITIVITY, ENDOMETRIAL CANCER, REDUCED CVD RISK ON ASPIRIN AND VITAMIN E
rs165599 3 G ANXIETY-RELATED PERSONALITY TRAITS, ADHD, SCHIZOPHRENIA
rs737865 2 G BUPROPION TREATMENT FOR SMOKING CESSATION
rs6269 5 G HYPERACTIVITY PARKINSON'S DISEASE SCHIZOPHRENIA MAJOR DEPRESSIVE DISORDER
rs4618 6 G FIBROMYALGIA, CHRONIC PAIN
rs4646312 6 T ESTROGEN ANDROGEN METABOLIZING
rs933271 3 C NICOTINE DEPENDANCE SCHIZOPHRENIA COCAINE PARANOIA IMPULSIVITY
ADVERSE DRUG REACTIONS ASSOCIATED WITH COMT
DRUG SNP ADVERSE REACTION ALLELE PUBMED
MODAFINIL rs4680POOR RESPONSE TO MODAFINILAA1
MODAFINIL rs4680THOSE WITH THE GG GENOTYPE RESPOND BETTER TO DRUG THERAPY (IMPROVED VIGOR AND WELL BEING). THOSE WITH THE AA GENOTYPE DO NOT RESPOND WELL TO DRUG THERAPYGG1
TISSUE DISTRIBUTION OF COMT
CATEGORY TISSUE
DIGESTIVE SYSTEM INTESTINE
ENDOCRINE SYSTEM ADRENAL GLAND
FEMALE REPRODUCTIVE MAMMARY GLAND
IMMUNE SYSTEM MONOCYTE
LACRIMAL APPARATUS LACRIMAL GLAND
SECRETIONS TEAR
PATHWAY REGULATION ASSOCIATED WITH COMT
PATHWAY EFFECT
CAUSAL ETIOLOGIC ASSOCIATIONS (INFERRED)COMT
ETIOLOGY MAGNITUDE
4-HYDROXYCOUMARINS2
6-MERCAPTOPURINE2
7,8-DIHYDRO-7,8-DIHYDROXYBENZO(A)PYRENE 9,10-OXIDE2
ABDOMINAL INJURIES2
ABORTIFACIENT AGENTS2
ACETAZOLAMIDE2
ACETIC ACIDS2
ACQUIRED IMMUNODEFICIENCY SYNDROME2
ACTINOID SERIES ELEMENTS2
ADENOMATOUS POLYPOSIS COLI2
ADRENAL CORTEX HORMONES2
ADRENERGIC AGENTS2
ADRENERGIC AGONISTS2
ADRENERGIC ANTAGONISTS2
AFFECTIVE DISORDERS, PSYCHOTIC2
AGROCHEMICALS2
AIR POLLUTANTS2
AIR POLLUTANTS, ENVIRONMENTAL2
AIR POLLUTION2
ALCOHOL-RELATED DISORDERS2
ALCOHOLIC BEVERAGES2
ALCOHOLS2
ALCOHOL DRINKING2
ALDEHYDES2
ALOPECIA2
ALPHA-THALASSEMIA2
ALUMINUM COMPOUNDS2
AMANTADINE2
AMINES2
AMINOPTERIN2
AMINO ACIDS, DIAMINO2
AMINO ACID METABOLISM, INBORN ERRORS2
AMNESIA2
AMPHETAMINE2
AMPHETAMINES2
AMYLOIDOSIS2
ANALGESICS2
ANDROSTENES2
ANEMIA2
ANEMIA, HEMOLYTIC2
ANEMIA, SICKLE CELL2
ANESTHESIA2
ANESTHESIA, GENERAL2
ANESTHESIA, INHALATION2
ANESTHETICS2
ANESTHETICS, GENERAL2
ANEURYSM2
ANGINA, UNSTABLE2
ANGINA PECTORIS2
ANGIOPLASTY2
ANGIOPLASTY, BALLOON2
ANGIOPLASTY, LASER2
ANGIOSPERMS2
ANILIDES2
ANILINE COMPOUNDS2
ANTACIDS2
ANTHELMINTICS2
ANTI-ALLERGIC AGENTS2
ANTI-ASTHMATIC AGENTS2
ANTI-BACTERIAL AGENTS2
ANTI-DYSKINESIA AGENTS2
ANTI-HIV AGENTS2
ANTI-INFECTIVE AGENTS2
ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL2
ANTIBODIES2
ANTIBODIES, MONOCLONAL2
ANTICHOLESTEREMIC AGENTS2
ANTIDEPRESSIVE AGENTS2
ANTIFUNGAL AGENTS2
ANTILIPEMIC AGENTS2
ANTIMETABOLITES2
ANTINEOPLASTIC AGENTS2
ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS2
ANTIOXIDANTS2
ANXIETY2
ANXIETY DISORDERS2
AORTIC ANEURYSM2
AORTIC VALVE STENOSIS2
ARRHYTHMIA2
ARSENIC2
ARTERIAL OCCLUSIVE DISEASES2
ARTERIOSCLEROSIS2
ARTERIOVENOUS MALFORMATIONS2
ARTERITIS2
ARTHRITIS, RHEUMATOID2
ASBESTOS2
ASPHYXIA NEONATORUM2
ASTHMA2
ATTENTION DEFICIT AND DISRUPTIVE BEHAVIOR DISORDERS2
AUTOIMMUNE DISEASES2
AUTOIMMUNE DISEASES OF THE NERVOUS SYSTEM2
AUTONOMIC NERVOUS SYSTEM DISEASES2
AZA COMPOUNDS2
BENZAMIDES2
BENZIMIDAZOLES2
BENZODIAZEPINES2
BENZOFURANS2
BENZOPYRANS2
BENZOPYRENES2
BIOLOGICAL PRODUCTS2
BIOPSY2
BIPHENYL COMPOUNDS2
BITES AND STINGS2
BLOOD COAGULATION FACTORS2
BONE DISEASES, DEVELOPMENTAL2
BONE MARROW TRANSPLANTATION2
BRAIN DAMAGE, CHRONIC2
BRAIN DISEASES2
BRAIN DISEASES, METABOLIC, INBORN2
BRAIN INJURIES2
BRAIN ISCHEMIA2
BRAIN NEOPLASMS2
BREAST DISEASES2
BREAST FEEDING2
BURNS2
BUTYROPHENONES2
CADMIUM COMPOUNDS2
CALCINOSIS2
CALCIUM COMPOUNDS2
CALCIUM METABOLISM DISORDERS2
CANNABINOIDS2
CAPTOPRIL2
CARBAMATES2
CARBOHYDRATES2
CARBOLINES2
CARBONATES2
CARBON COMPOUNDS, INORGANIC2
CARCINOGENS2
CARCINOMA2
CARCINOMA IN SITU2
CARDIAC PACING, ARTIFICIAL2
CARDIAC SURGICAL PROCEDURES2
CARDIOMEGALY2
CARDIOMYOPATHIES2
CARDIOMYOPATHY, HYPERTROPHIC2
CARDIOVASCULAR ABNORMALITIES2
CARDIOVASCULAR AGENTS2
CAROTENOIDS2
CAROTID ARTERY DISEASES2
CARRIER PROTEINS2
CASTRATION2
CATARACT EXTRACTION2
CATECHOLAMINES2
CATHETERIZATION2
CENTRAL NERVOUS SYSTEM AGENTS2
CENTRAL NERVOUS SYSTEM CYSTS2
CENTRAL NERVOUS SYSTEM DEPRESSANTS2
CENTRAL NERVOUS SYSTEM STIMULANTS2
CEREBELLAR DISEASES2
CEREBRAL ARTERIAL DISEASES2
CEREBRAL HEMORRHAGE2
CEREBRAL INFARCTION2
CEREBROVASCULAR ACCIDENT2
CEREBROVASCULAR DISORDERS2
CHILD BEHAVIOR DISORDERS2
CHILD DEVELOPMENT DISORDERS, PERVASIVE2
CHLAMYDOPHILA INFECTIONS2
CHLORIDES2
CHLORINE COMPOUNDS2
CHLOROBENZENES2
CHOLANGIOGRAPHY2
CHOLECYSTECTOMY2
CHOLELITHIASIS2
CHOLESTEROL2
CHOLINERGIC AGENTS2
CHROMATES2
CHROMOSOME DISORDERS2
CICATRIX2
COCAINE2
COGNITION DISORDERS2
COLD2
COLITIS2
COLLAGEN DISEASES2
COLONOSCOPY2
COLORECTAL NEOPLASMS2
COLORING AGENTS2
CONNECTIVE TISSUE DISEASES2
CONSTIPATION2
CONTRACEPTIVES, ORAL2
CONTRACEPTIVE AGENTS2
CONTRACEPTIVE AGENTS, FEMALE2
CONTRACEPTIVE DEVICES, MALE2
CONVULSIVE THERAPY2
CORONARY ARTERY BYPASS2
CORONARY DISEASE2
CORONARY STENOSIS2
CORONARY VASOSPASM2
CORTICOTROPIN2
COSMETICS2
COSMIC RADIATION2
CRANIAL IRRADIATION2
CRANIOCEREBRAL TRAUMA2
CRANIOFACIAL ABNORMALITIES2
CRANIOFACIAL DYSOSTOSIS2
CRANIOSYNOSTOSES2
CRYOTHERAPY2
CYCLOHEXANES2
CYCLOPHOSPHAMIDE2
CYCLOSPORINS2
CYSTEINE2
CYSTICERCOSIS2
CYSTS2
CYTODIAGNOSIS2
CYTOMEGALOVIRUS INFECTIONS2
DAIRY PRODUCTS2
DEFICIENCY DISEASES2
DEMENTIA2
DEMYELINATING DISEASES2
DENTAL CARE2
DENTAL DISINFECTANTS2
DENTAL MATERIALS2
DEOXYCHOLIC ACID2
DEOXYCYTIDINE2
DEPRESSION2
DEPRESSIVE DISORDER2
DERMATOLOGIC AGENTS2
DEXAMETHASONE2
DIABETES, GESTATIONAL2
DIABETES MELLITUS, TYPE 12
DIABETES MELLITUS, TYPE 22
DIABETIC ANGIOPATHIES2
DIALYSIS2
DIDEOXYNUCLEOSIDES2
DIET2
DIETARY CARBOHYDRATES2
DIETARY FATS2
DIETARY FATS, UNSATURATED2
DIETARY SUPPLEMENTS2
DIGESTIVE SYSTEM ABNORMALITIES2
DIGESTIVE SYSTEM SURGICAL PROCEDURES2
DIHYDROPYRIDINES2
DIHYDROXYPHENYLALANINE2
DIOXINS2
DIPEPTIDES2
DIPHENHYDRAMINE2
DISEASE SUSCEPTIBILITY2
DISINFECTANTS2
DISULFIDES2
DOPAMINE AGENTS2
DOXORUBICIN2
DUST2
DWARFISM2
ELECTRICITY2
ELECTROMAGNETIC FIELDS2
EMBOLISM2
EMBOLIZATION, THERAPEUTIC2
EMPHYSEMA2
ENALAPRIL2
ENCEPHALITIS2
ENCEPHALITIS, ARBOVIRUS2
ENCEPHALOMALACIA2
ENDARTERECTOMY2
ENDOSCOPY2
ENDOSULFAN2
ENDOTOXINS2
ENVIRONMENTAL EXPOSURE2
ENVIRONMENTAL POLLUTANTS2
ENVIRONMENTAL POLLUTION2
ENZYME INHIBITORS2
EPILEPSIES, PARTIAL2
EPILEPSY2
EPILEPSY, GENERALIZED2
EPINEPHRINE2
EPOXY COMPOUNDS2
EPSTEIN-BARR VIRUS INFECTIONS2
ERGOLINES2
ERGONOVINE2
ERGOTAMINES2
ERYTHROMYCIN2
ESOPHAGEAL DISEASES2
ESTRADIOL2
ESTRADIOL CONGENERS2
ESTROGENS2
ESTROGENS, NON-STEROIDAL2
ESTROGEN RECEPTOR MODULATORS2
ETHANOL2
ETHANOLAMINES2
EXCITATORY AMINO ACID AGENTS2
EXTRACORPOREAL CIRCULATION2
EYE ABNORMALITIES2
FANCONI ANEMIA2
FATIGUE2
FATS, UNSATURATED2
FATTY ACIDS2
FATTY ACIDS, ESSENTIAL2
FATTY ACIDS, OMEGA-32
FATTY ACIDS, OMEGA-62
FATTY ACIDS, UNSATURATED2
FENFLURAMINE2
FERTILITY AGENTS2
FERTILIZATION IN VITRO2
FETAL HYPOXIA2
FEVER2
FIBROBLAST GROWTH FACTOR 22
FISTULA2
FLOXURIDINE2
FLUORINE2
FLUOROURACIL2
FOLIC ACID2
FOOD2
FOOD, FORMULATED2
FOOD ADDITIVES2
FRAGILE X SYNDROME2
FRUIT2
GABA AGENTS2
GASTROENTERITIS2
GASTROINTESTINAL AGENTS2
GAS POISONING2
GENETIC DISEASES, INBORN2
GENETIC DISEASES, X-LINKED2
GENITAL DISEASES, FEMALE2
GLUCAGON2
GLUTAMATES2
GLYCEROL2
GOITER2
GONADAL DYSGENESIS2
GONADAL STEROID HORMONES2
GONADOTROPINS2
GRAFT OCCLUSION, VASCULAR2
GRAFT REJECTION2
GRAM-NEGATIVE BACTERIAL INFECTIONS2
GRAVITY, ALTERED2
GROWTH DISORDERS2
GROWTH HORMONE2
GUANIDINES2
GYNECOLOGIC SURGICAL PROCEDURES2
HAIR DISEASES2
HAIR PREPARATIONS2
HAMARTOMA2
HEARING DISORDERS2
HEARING LOSS2
HEARING LOSS, SENSORINEURAL2
HEART BYPASS, RIGHT2
HEART CATHETERIZATION2
HEART DEFECTS, CONGENITAL2
HEART DISEASES2
HEART FAILURE, CONGESTIVE2
HEART RUPTURE, POST-INFARCTION2
HEART SEPTAL DEFECTS, ATRIAL2
HEART VALVE DISEASES2
HEMATOMA2
HEMATOMA, SUBDURAL2
HEMODILUTION2
HEMOSTATICS2
HEPTACHLOR EPOXIDE2
HERBICIDES2
HEREDITARY MOTOR AND SENSORY NEUROPATHIES2
HEREDODEGENERATIVE DISORDERS, NERVOUS SYSTEM2
HERNIA, ABDOMINAL2
HERNIA, DIAPHRAGMATIC2
HERPESVIRIDAE INFECTIONS2
HETEROCYCLIC COMPOUNDS2
HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS2
HIP FRACTURES2
HISTAMINE ANTAGONISTS2
HISTAMINE H1 ANTAGONISTS2
HISTIOCYTOSIS, LANGERHANS-CELL2
HISTIOCYTOSIS, NON-LANGERHANS-CELL2
HIV INFECTIONS2
HOMOCYSTEINE2
HORMONES2
HORMONE ANTAGONISTS2
HORMONE REPLACEMENT THERAPY2
HOT FLASHES2
HYDANTOINS2
HYDRAZINES2
HYDROCARBONS, BROMINATED2
HYDROCARBONS, CHLORINATED2
HYDROCEPHALUS2
HYDROCORTISONE2
HYDROXYBENZOIC ACIDS2
HYPERALDOSTERONISM2
HYPEREMESIS GRAVIDARUM2
HYPERGLYCEMIA2
HYPERINSULINISM2
HYPERLIPIDEMIA2
HYPERLIPOPROTEINEMIA2
HYPERPARATHYROIDISM2
HYPERSENSITIVITY2
HYPERSENSITIVITY, IMMEDIATE2
HYPERTENSION2
HYPERTHYROIDISM2
HYPERTRIGLYCERIDEMIA2
HYPOGLYCEMIA2
HYPOGONADISM2
HYPOPARATHYROIDISM2
HYPOTHALAMIC DISEASES2
HYPOTHYROIDISM2
HYPOXIA-ISCHEMIA, BRAIN2
HYSTERECTOMY2
IMIDAZOLES2
IMMERSION2
IMMUNOGLOBULIN FAB FRAGMENTS2
IMMUNOGLOBULIN G2
IMMUNOLOGIC DEFICIENCY SYNDROMES2
IMMUNOSUPPRESSION2
IMMUNOSUPPRESSIVE AGENTS2
IMMUNOTOXINS2
INFARCTION2
INFECTION2
INFERTILITY2
INFLAMMATION2
INFLAMMATORY BOWEL DISEASES2
INFRATENTORIAL NEOPLASMS2
INSULIN2
INTERFERON-ALPHA2
INTESTINAL DISEASES2
INTESTINAL POLYPOSIS2
INTRACRANIAL ARTERIOSCLEROSIS2
INTRAUTERINE DEVICES2
IRON COMPOUNDS2
ISOFLAVONES2
ISOQUINOLINES2
ISOSORBIDE DINITRATE2
ISOTHIOCYANATES2
JOINT DISEASES2
KAVA2
KIDNEY DISEASES2
KIDNEY FAILURE2
KIDNEY TRANSPLANTATION2
LACTONES2
LANGUAGE DISORDERS2
LAPAROSCOPY2
LENTIGO2
LEUKOCYTOSIS2
LIGHT2
LIPIDS2
LITHOTRIPSY2
LIVER CIRRHOSIS2
LUNG DISEASES2
LUNG DISEASES, INTERSTITIAL2
LUNG DISEASES, OBSTRUCTIVE2
LUNG NEOPLASMS2
LUPUS ERYTHEMATOSUS, SYSTEMIC2
LYME DISEASE2
LYMPHATIC DISEASES2
LYMPHEDEMA2
LYMPHOMA2
LYMPHOMA, B-CELL2
MACROLIDES2
MAGNETICS2
MAGNETIC RESONANCE SPECTROSCOPY2
MALABSORPTION SYNDROMES2
MAMMAPLASTY2
MANDIBULOFACIAL DYSOSTOSIS2
MASTECTOMY2
MEAT2
MEDROXYPROGESTERONE2
MEMORY DISORDERS2
MENINGEAL NEOPLASMS2
MENINGITIS2
MENINGITIS, BACTERIAL2
MENINGOENCEPHALITIS2
MENSTRUATION DISTURBANCES2
MENTAL DISORDERS2
MENTAL RETARDATION2
METABOLIC DISEASES2
METABOLISM, INBORN ERRORS2
METALS2
METALS, HEAVY2
METALS, LIGHT2
METHIONINE SULFOXIMINE2
METHYL ETHERS2
MILK2
MINERALS2
MITOCHONDRIAL DISEASES2
MORPHINANS2
MOUTH ABNORMALITIES2
MOUTH DISEASES2
MOVEMENT DISORDERS2
MULTIPLE SCLEROSIS2
MUSCULAR DISEASES2
MUSCULOSKELETAL ABNORMALITIES2
MUTAGENS2
MYCOTOXINS2
MYDRIATICS2
MYOCARDIAL INFARCTION2
MYOCARDIAL REVASCULARIZATION2
NAPHTHALENES2
NEOPLASMS, MULTIPLE PRIMARY2
NEOPLASMS, NEUROEPITHELIAL2
NEOPLASMS, VASCULAR TISSUE2
NEURAL TUBE DEFECTS2
NEUROCUTANEOUS SYNDROMES2
NEURODEGENERATIVE DISEASES2
NEUROFIBROMATOSES2
NEUROPEPTIDES2
NEUROTOXINS2
NEUROTRANSMITTER UPTAKE INHIBITORS2
NIACINAMIDE2
NICOTINIC AGONISTS2
NITRATES2
NITRILES2
NITROGEN OXIDES2
NITROSOUREA COMPOUNDS2
NITRO COMPOUNDS2
NOCARDIA INFECTIONS2
NOISE2
NORGESTREL2
NUCLEAR PROTEINS2
NUTRITION DISORDERS2
OBESITY2
OCULAR MOTILITY DISORDERS2
OLIGOPEPTIDES2
ORGANOPHOSPHORUS COMPOUNDS2
ORGANOPLATINUM COMPOUNDS2
ORGANOSELENIUM COMPOUNDS2
ORGANOTHIOPHOSPHORUS COMPOUNDS2
ORTHOMYXOVIRIDAE INFECTIONS2
OSTEOPOROSIS2
OVARIAN CYSTS2
OXIDANTS2
OXIDES2
OXIDOPAMINE2
OXYGEN2
OXYTOCIN2
PANCREATIC DISEASES2
PANCREATITIS2
PAPILLOMAVIRUS INFECTIONS2
PAPOVAVIRIDAE INFECTIONS2
PARACENTESIS2
PARANEOPLASTIC SYNDROMES, NERVOUS SYSTEM2
PARASYMPATHOLYTICS2
PARATHION2
PARKINSONIAN DISORDERS2
PARKINSON DISEASE, SECONDARY2
PENTANOIC ACIDS2
PEPTIC ULCER2
PEPTIDES2
PERIODONTAL DISEASES2
PERIODONTITIS2
PERIOPERATIVE CARE2
PERIPHERAL NERVOUS SYSTEM DISEASES2
PERITONEAL DISEASES2
PERSONALITY DISORDERS2
PESTICIDES2
PHARMACEUTICAL PREPARATIONS2
PHARMACEUTIC AIDS2
PHENANTHRENES2
PHENETHYLAMINES2
PHENOBARBITAL2
PHENOLS2
PHENOTHIAZINES2
PHENYLACETATES2
PHENYLKETONURIAS2
PHENYL ETHERS2
PHOSPHORUS COMPOUNDS2
PHTHALIC ACIDS2
PIPECOLIC ACIDS2
PIPERAZINES2
PIPERIDINES2
PITUITARY DISEASES2
PLATELET AGGREGATION INHIBITORS2
PNEUMONIA2
PNEUMOPERITONEUM, ARTIFICIAL2
POLIOMYELITIS2
POLYCHLORINATED BIPHENYLS2
POLYCYCLIC HYDROCARBONS, AROMATIC2
POLYSACCHARIDES2
PRE-ECLAMPSIA2
PREGNANCY IN DIABETICS2
PREGNENEDIONES2
PRENATAL DIAGNOSIS2
PROGESTERONE2
PROGESTERONE CONGENERS2
PROPANOLAMINES2
PROPIONIC ACIDS2
PROSTAGLANDINS E, SYNTHETIC2
PROSTATECTOMY2
PROSTATIC DISEASES2
PROSTHESES AND IMPLANTS2
PROSTHESIS IMPLANTATION2
PROTEASE INHIBITORS2
PROTEINURIA2
PROTEIN DEFICIENCY2
PROTOZOAN INFECTIONS, ANIMAL2
PSYCHOTROPIC DRUGS2
PUNCTURES2
PURPURA2
PUVA THERAPY2
PYRETHRINS2
PYRIDINES2
PYRIDINIUM COMPOUNDS2
PYRIMIDINES2
PYRROLES2
QUATERNARY AMMONIUM COMPOUNDS2
QUINOXALINES2
RADIATION, NONIONIZING2
RADIATION-PROTECTIVE AGENTS2
RADIOGRAPHY2
RADIOTHERAPY2
RADON2
RECTAL NEOPLASMS2
RENAL DIALYSIS2
REPERFUSION INJURY2
RESPIRATORY FUNCTION TESTS2
RESPIRATORY HYPERSENSITIVITY2
RESPIRATORY TRACT INFECTIONS2
RETINITIS PIGMENTOSA2
RETINOIDS2
RHINITIS2
RNA, DOUBLE-STRANDED2
RUBBER2
RUBELLA2
SALICYLIC ACIDS2
SCHIZOPHRENIA2
SCLERODERMA, SYSTEMIC2
SCOPOLAMINE DERIVATIVES2
SENSATION DISORDERS2
SEROTONIN AGENTS2
SEXUALLY TRANSMITTED DISEASES2
SEXUAL DYSFUNCTIONS, PSYCHOLOGICAL2
SILICONES2
SILICON DIOXIDE2
SILICOSIS2
SKIN DISEASES2
SKIN DISEASES, VASCULAR2
SKULL NEOPLASMS2
SLEEP APNEA, OBSTRUCTIVE2
SLEEP APNEA SYNDROMES2
SLEEP DISORDERS2
SMOKE2
SMOKING2
SOIL POLLUTANTS2
SOLANACEOUS ALKALOIDS2
SOLVENTS2
SOMATOMEDINS2
SOYBEANS2
SPINAL CORD INJURIES2
SPINOCEREBELLAR ATAXIAS2
STERILIZATION, REPRODUCTIVE2
STEROIDS2
STILBENES2
STOMATITIS2
STRESS2
STRESS, PSYCHOLOGICAL2
SUBARACHNOID HEMORRHAGE2
SUBSTANCE-RELATED DISORDERS2
SUCROSE2
SULFAMETHOXAZOLE2
SULFHYDRYL COMPOUNDS2
SULFONAMIDES2
SULFONYLUREA COMPOUNDS2
SUNLIGHT2
SYMPATHECTOMY2
SYNDACTYLY2
TACHYCARDIA, SUPRAVENTRICULAR2
TAMOXIFEN2
TAXOIDS2
TELANGIECTASIS2
TERATOGENS2
TESTOSTERONE2
TESTOSTERONE CONGENERS2
TETANUS TOXOID2
THALASSEMIA2
THEOPHYLLINE2
THIAZOLES2
THIOPHENES2
THORACIC OUTLET SYNDROME2
THORACIC SURGICAL PROCEDURES2
THROMBOCYTOPENIA2
THROMBOLYTIC THERAPY2
THROMBOSIS2
THYROID DISEASES2
THYROID HORMONES2
THYROID NEOPLASMS2
TOBACCO2
TOLUENE2
TRANQUILIZING AGENTS2
TRANS-ACTIVATORS2
TRANSCRIPTION FACTORS2
TRANSITION ELEMENTS2
TRANSPLANTATION, HOMOLOGOUS2
TRIALKYLTIN COMPOUNDS2
TRIAZINES2
TRIAZOLES2
TRIHALOMETHANES2
TRIMETHOPRIM2
TUMOR VIRUS INFECTIONS2
UREMIA2
URETERAL DISEASES2
UROLOGIC DISEASES2
VASCULAR DISEASES2
VASCULAR FISTULA2
VASCULITIS2
VASCULITIS, CENTRAL NERVOUS SYSTEM2
VASCULITIS, HYPERSENSITIVITY2
VASOCONSTRICTOR AGENTS2
VASOPRESSINS2
VENTRICULAR DYSFUNCTION2
VERTEBROBASILAR INSUFFICIENCY2
VIBRATION2
VINCA ALKALOIDS2
VIRAL VACCINES2
VISION DISORDERS2
VITAMINS2
VITAMIN A2
VITAMIN B 12 DEFICIENCY2
VITAMIN B DEFICIENCY2
VITAMIN D2
VITAMIN D DEFICIENCY2
WATER-ELECTROLYTE IMBALANCE2
WATER POLLUTANTS2
WOUNDS, NONPENETRATING2
WOUNDS, PENETRATING2
X-RAYS2
XANTHINES2
XANTHONES2
ZINC COMPOUNDS2
METABOLOME ASSOCIATIONS: COMT
HMDB ID METABOLITE
HMDB01398 GUAIACOL
HMDB00957 PYROCATECHOL
HMDB00819 NORMETANEPHRINE
HMDB00609 DIHYDROXYPHENYLALANINE