DOXORUBICIN PHARMACOKINETICS PATHWAY (PW:0001565)
Description Doxorubucin (DOX, trade name Adriamycin) is an anthracycline derived from Streptomyces bacterium Streptomyces peucetius var. caesius . DOX is used in the treatment of several solid cancers, leukemia and lymphomas. The drug is composed of a planar aromatic ring with an anthraquinone chromophore and a sugar group. Once taken up by the cell and inside the nucleus for which it has a high affinity, the planar ring structure intercalates between adjacent DNA base pairs, preferentially GC base pairs. DOX can form DNA adducts, binds to DNA and topoisomerases and inhibits DNA replication and transcription. It promotes DNA double-strand breaks (DSBs) and the DNA damage prompts various responses, including cell cycle arrest and apoptosis, primarily via activation of p53 pathway but also independent of it, with beneficial, if tumor cells, or otherwise detrimental consequences. While toxic to the tumor cell, DOX is also toxic to all other cell types. The cardiotoxicity of the drug is the main and the most severe adverse effect, and the cardiomyopathies associated with DOX can eventually lead to heart failure. The formation of reactive oxygen species (ROS), impaired iron homeostasis and mitochondrial dysfunction are thought to underlie the cardiotoxicity of DOX. Although more than 50% of DOX is eliminated unchanged, the drug undergoes several types of transformation such as two- and one-electron reduction and to a smaller extent deglycosidation. Free radical generation is a feature of DOX metabolism. The drug can interact with iron and generate hydroxyl radical and with the iron-responsive elements (IRE) regions of mRNAs, it can impact on the function of iron regulatory proteins (IRPs) and disturb iron homeostasis. In addition, DOX localizes to mitochondria, forms adducts with mitochondrial DNA, interacts with cardiolipin - an essential component of inner mitochondrial membrane, and is capable of impacting on a number of proteins/enzymes important for mitochondrial function. Doxorubicin is also administered as a pegylated liposomal product.
The uptake of DOX is mediated by Slc22a16, while several transporters are involved in the elimination of the drug. Those include Abcb1, Abcc2 and Abcc3, Abcg2 and Ralbp1. As mentioned, there are several routes of DOX processing. The most common one is the two-electron reduction, followed by the one-electron reduction. The Cbr1 and Cbr3, and the Akr1a1 and Akr1c3 carry out the two-electron reduction. Xdh and Nqo1 and the endothelial nitric oxide synthase Nos3, carry out the one-electron reduction. The deglycosidation of DOX accounts for only ~1-2% of processing and the enzymes involved are still to be characterized. Both the one-electron and the deglycosidation reactions generate ROS. In the one-electron reduction the quinone moiety generates a semiquinone radical that regenerates the parent quinone by reducing molecular oxygen to ROS. It is believed that further processing of metabolites via glucuronidation, sulfation or methylation is necessary before they can be eliminated. To see the ontology report for annotations, GViewer and download, click here
...(less)
Pathway Diagram:
Genes in Pathway:
G
Abcb1a
ATP binding cassette subfamily B member 1A
4
22,339,829
22,517,642
RGD:10395261 RGD:10402751
G
Abcc1
ATP binding cassette subfamily C member 1
10
549,537
672,235
RGD:10402751
G
Abcc2
ATP binding cassette subfamily C member 2
1
263,554,426
263,612,556
RGD:10395261 RGD:10402751
G
Abcc3
ATP binding cassette subfamily C member 3
10
82,047,308
82,116,928
RGD:10395261
G
Abcg2
ATP binding cassette subfamily G member 2
4
88,765,441
88,890,268
RGD:10395261 RGD:10402751
G
Akr1a1
aldo-keto reductase family 1 member A1
5
135,482,068
135,498,693
RGD:10395261 RGD:10402751 RGD:10395262
G
Akr1c3
aldo-keto reductase family 1, member C3
17
69,761,126
69,778,021
RGD:10395261 RGD:10402751
G
Cbr1
carbonyl reductase 1
11
33,813,041
33,815,418
RGD:10395261 RGD:10402751 RGD:10395262
G
Cbr3
carbonyl reductase 3
11
33,909,417
33,917,674
RGD:10395261 RGD:10402751 RGD:10395262
G
Ndufs2
NADH:ubiquinone oxidoreductase core subunit S2
13
89,606,848
89,623,506
RGD:10402751
G
Ndufs3
NADH:ubiquinone oxidoreductase core subunit S3
3
79,721,686
79,728,863
RGD:10402751
G
Ndufs7
NADH:ubiquinone oxidoreductase core subunit S7
7
12,318,776
12,326,403
RGD:10402751
G
Nos3
nitric oxide synthase 3
4
7,321,908
7,342,404
RGD:10395262 RGD:10402751
G
Nqo1
NAD(P)H quinone dehydrogenase 1
19
38,422,210
38,437,103
RGD:10395262 RGD:10402751
G
Por
cytochrome p450 oxidoreductase
12
23,998,411
24,017,063
RGD:10402751
G
Ralbp1
ralA binding protein 1
9
113,579,107
113,598,477
RGD:10395261 RGD:10402751
G
Slc22a16
solute carrier family 22 member 16
20
45,658,398
45,669,192
RGD:10395261 RGD:10402751
G
Xdh
xanthine dehydrogenase
6
25,149,570
25,211,273
RGD:10395262 RGD:10402751
Pathway Gene Annotations
Disease Annotations Associated with Genes in the doxorubicin pharmacokinetics pathway
Abcb1a Adrenocortical Carcinoma , Anthracycline-induced Cardiotoxicity , Arthritis, Experimental , Arthritis, Rheumatoid , asthma , Behcet Syndrome , Breast Neoplasms , Carcinoma , Carcinoma, Ductal, Breast , Carcinoma, Hepatocellular , Carcinoma, Renal Cell , Carcinoma, Squamous Cell of Head and Neck , Chemical and Drug Induced Liver Injury , chronic myeloid leukemia , Colorectal Neoplasms , Crohn Disease , diabetes mellitus, experimental , Disease Progression , Drug-induced Neutropenia , Drug-Related Side Effects and Adverse Reactions , Encephalitis , Endotoxemia , Eosinophilia , Epilepsy , Epilepsy, Familial Temporal Lobe, 3 , Epilepsy, Temporal Lobe , Escherichia Coli Infections , Esophageal Neoplasms , Fetal Growth Retardation , Genetic Predisposition to Disease , Heart Defects, Congenital , Heart Diseases , Hematologic Neoplasms , HIV Infections , Hyperlipidemias , Hypotension, Orthostatic , Inflammation , inflammatory bowel disease 13 , Intestinal Polyposis , Kidney Diseases , Kidney Failure, Chronic , kidney neoplasms , Liver Cirrhosis, Experimental , Lymphoma, Extranodal NK-T-Cell , Lymphoma, Large B-Cell, Diffuse , Mammary Neoplasms, Experimental , marijuana abuse , Mental Disorders , Nasal Polyps , Nausea , necrotizing enterocolitis , Neoplasm Metastasis , neoplasms , Neoplasms, Germ Cell and Embryonal , Nervous System Diseases , neuroblastoma , neurotoxicity syndromes , Neutropenia , non-small cell lung carcinoma , nonalcoholic fatty liver disease , Ovarian Neoplasms , Pain , Pain, Postoperative , Parkinson's Disease , Parkinson's Disease, Secondary , Peripheral Nervous System Diseases , Pleomorphic Xanthoastrocytoma , Poisoning , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Reperfusion Injury , Rhinitis, Allergic , Seizures , Sleep Apnea, Obstructive , Status Epilepticus , Translocation, Genetic , type 2 diabetes mellitus , Vomiting , Wilms tumor Abcc1 asthma , breast cancer, familial , Breast Neoplasms , Carcinoma, Squamous Cell of Head and Neck , Chemical and Drug Induced Liver Injury , Colorectal Neoplasms , Disease Progression , Drug-Related Side Effects and Adverse Reactions , Heart Diseases , Hypertension , Peripheral Nervous System Diseases , Pneumonia, Bacterial , Pseudoxanthoma Elasticum , Pulmonary Disease, Chronic Obstructive , Schizophrenia Abcc2 Alopecia , Arthritis, Rheumatoid , Carcinoma, Squamous Cell of Head and Neck , Chemical and Drug Induced Liver Injury , cholangiocarcinoma , Cholestasis , chronic myeloid leukemia , Colorectal Neoplasms , diabetes mellitus, experimental , Drug Hypersensitivity , Drug-Induced Immune Thrombocytopenia , Drug-induced Neutropenia , Drug-Related Side Effects and Adverse Reactions , Endotoxemia , esophageal squamous cell carcinoma , Fatty Liver , Gastrointestinal Diseases , Heart Diseases , Hyperbilirubinemia , Jaundice, Chronic Idiopathic , Kidney Failure, Chronic , Liver Cirrhosis, Biliary , Liver Cirrhosis, Experimental , Liver Failure, Acute , Nervous System Diseases , non-small cell lung carcinoma , Pancreatic Neoplasms , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Seizures , Status Epilepticus , type 2 diabetes mellitus Abcc3 Arthritis, Rheumatoid , Carcinoma, Hepatocellular , Cholestasis , Colorectal Neoplasms , diabetes mellitus, experimental , Fatty Liver , Hepatomegaly , Hyperbilirubinemia , Hyperprolactinemia , Jaundice, Chronic Idiopathic , Kidney Diseases , Kidney Failure, Chronic , Leukemia, Myeloid, Acute , nonalcoholic fatty liver disease , Pancreatic Neoplasms , Smith-Magenis syndrome Abcg2 acute megakaryoblastic leukemia , Adenoma , Arthritis, Experimental , Arthritis, Rheumatoid , Breast Neoplasms , Carcinoma, Renal Cell , Carcinoma, Squamous Cell of Head and Neck , chronic myeloid leukemia , Colorectal Neoplasms , Diabetes Mellitus , diabetes mellitus, experimental , Drug-Related Side Effects and Adverse Reactions , gout , Hyperparathyroidism, Secondary , Hyperuricemia , Leukemia, Myeloid, Acute , Liver Cirrhosis, Biliary , Liver Injury , lymphocytic leukemia, chronic, B-cell , Lymphoma, B-Cell , Lymphoma, Large B-Cell, Diffuse , Mammary Neoplasms, Experimental , Multiple Myeloma , Nervous System Diseases , neurotoxicity syndromes , Ovarian Neoplasms , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , Reperfusion Injury , Status Epilepticus , URIC ACID CONCENTRATION, SERUM, QUANTITATIVE TRAIT LOCUS 1 Akr1a1 necrotizing enterocolitis Akr1c3 Carcinoma, Intraductal, Noninfiltrating , castration-resistant prostatic neoplasms , Cell Transformation, Neoplastic , Disorders of Sex Development , Endometrial Neoplasms , Endometriosis , Leukemia , Liver Cirrhosis, Experimental , Myeloproliferative Disorders , Neoplasms, Hormone-Dependent , obesity , Polycystic Ovary Syndrome , Pre-Eclampsia , Precursor B-Cell Lymphoblastic Leukemia-Lymphoma , Precursor T-Cell Lymphoblastic Leukemia-Lymphoma , prostate cancer , prostatic neoplasms , Stomach Neoplasms Cbr1 Carcinoma, Hepatocellular , cardiomyopathy , Colonic Neoplasms , diabetes mellitus, experimental , Fever , irritant dermatitis , Kidney Failure, Chronic , prostatic neoplasms , Renal Insufficiency, Chronic Cbr3 Mouth Neoplasms Ndufs2 cardiomyopathy , Cardiomyopathy, Hypertrophic , diabetes mellitus, experimental , inherited metabolic disorder , Leigh Disease , Mitochondrial Complex I Deficiency , Mitochondrial Encephalomyopathies , Multiple Sclerosis Ndufs3 Breast Neoplasms , diabetes mellitus, experimental , Leigh Disease , Leigh Syndrome Due To Mitochondrial Complex I Deficiency , Mitochondrial Complex I Deficiency , Optic Atrophy Ndufs7 bipolar disorder , Guanidinoacetate Methyltransferase Deficiency , Leigh Disease , Leigh Syndrome Due To Mitochondrial Complex I Deficiency , Mitochondrial Complex I Deficiency Nos3 Abruptio Placentae , Acute Chest Syndrome , Acute Kidney Injury , adenocarcinoma , Alzheimer's Disease , angle-closure glaucoma , Arteriosclerosis , Arteriovenous Fistula , Arthritis, Experimental , asthma , atherosclerosis , Atrial Fibrillation , Behcet Syndrome , Brain Ischemia , Breast Neoplasms , Bronchial Hyperreactivity , bronchiolitis obliterans , Cardiomegaly , cardiomyopathy , Cardiotoxicity , cardiovascular system disease , Carotid Artery Injuries , Cerebral Infarction , Child Behavior Disorders , Cholestasis , Cleft Lip , cleft palate , Colitis , Coronary Artery Disease , Coronary Vasospasm , Cystic Fibrosis , diabetes mellitus, experimental , Diabetic Angiopathies , Diabetic Cardiomyopathies , Diabetic Gastroparesis , Diabetic Nephropathies , Diabetic Retinopathy , drug-induced enteropathy , Endometrial Neoplasms , Endotoxemia , Erectile Dysfunction , Esophageal Neoplasms , essential hypertension , Fetal Growth Retardation , gastric ulcer , Glaucoma, Primary Open Angle , glioma , Graft Occlusion, Vascular , Hearing Loss, Sudden , Heart Failure , hepatopulmonary syndrome , Hernia, Diaphragmatic , Hernias, Diaphragmatic, Congenital , Huntington's Disease , Hyperemia , Hyperglycemia , hyperinsulinism , Hyperlipidemias , Hyperoxia , Hypertension , Hypertension Resistant to Conventional Therapy , Hypertension, Pregnancy-Induced , Hypertension, Renal , Hypertension, Renovascular , Hypertriglyceridemia , Hypertrophy, Left Ventricular , Hypertrophy, Right Ventricular , Hypothyroidism , Hypoxia , Hypoxia, Brain , Infertility, Male , Insulin Resistance , intestinal perforation , Intestinal Reperfusion Injury , Intimal Hyperplasia , Intracranial Aneurysm , Intracranial Hemorrhages , Irritable Bowel Syndrome , Ischemia , Kidney Failure, Chronic , Kidney Reperfusion Injury , Leiomyoma , Leukemia, Myeloid, Acute , Limb Ischemia , Liver Cirrhosis , Liver Cirrhosis, Experimental , Liver Failure, Acute , Liver Reperfusion Injury , Lung Diseases , Lung Reperfusion Injury , lymphangioleiomyomatosis , Lymphatic Metastasis , macular retinal edema , Metabolic Syndrome X , Migraine Disorders , Myocardial Infarction , Myocardial Ischemia , Myocardial Reperfusion Injury , Nasal Polyps , necrotizing enterocolitis , Neoplasm Metastasis , neoplasms , Nephritis , obesity , Optic Neuropathy, Ischemic , Ovarian Neoplasms , overnutrition , Pain , perennial allergic rhinitis , Phyllodes Tumor , Polycystic Kidney Diseases , portal hypertension , Pre-Eclampsia , Precursor Cell Lymphoblastic Leukemia-Lymphoma , prostatic neoplasms , Pulmonary Disease, Chronic Obstructive , Pulmonary Edema , pulmonary embolism , Pulmonary Emphysema , pulmonary eosinophilia , pulmonary hypertension , Pulmonary Hypertension, Hypoxia-Induced , Radiation Pneumonitis , Renal Insufficiency, Chronic , Reperfusion Injury , Respiratory Hypersensitivity , Retina Reperfusion Injury , Retinal Degeneration , Retinopathy of Prematurity , Sepsis , Shock, Hemorrhagic , sickle cell anemia , Sleep Apnea, Central , Sleep Apnea, Obstructive , Spinal Cord Compression , Spinal Cord Injuries , Stomach Neoplasms , Stroke , Subarachnoid Hemorrhage , Tachycardia, Ventricular , Telangiectasis , Testis Reperfusion Injury , Thromboembolism , Thrombotic Microangiopathies , transient cerebral ischemia , Transplant Rejection , type 1 diabetes mellitus , type 2 diabetes mellitus , Uremia , ureteral obstruction , urinary bladder cancer , urinary bladder neck obstruction , Vasculitis , Vaso-occlusive Crisis , Venous Thrombosis , Ventricular Dysfunction, Right , Ventricular Premature Complexes , Vestibular Diseases , Vulvar Neoplasms , Wet Macular Degeneration Nqo1 Acute Kidney Injury , Acute Lung Injury , Arthritis, Experimental , asthma , Brain Injuries , Breast Neoplasms , Carbon Tetrachloride Poisoning , Carcinoma, Small Cell , Cerebral Hemorrhage , Chemical and Drug Induced Liver Injury , Cholestasis , Chromosome 8, Trisomy , chronic myeloid leukemia , Colonic Neoplasms , Colorectal Neoplasms , Dermatitis, Contact , diabetes mellitus, experimental , Diabetic Nephropathies , Fatty Liver , Hemolytic-Uremic Syndrome , Hemorrhage , Hyperglycemia , Hyperoxia , Hyperoxic Lung Injury , Hypertension , Hypertrophy, Left Ventricular , Infarction, Middle Cerebral Artery , Intestinal Reperfusion Injury , Kidney Diseases , Kidney Reperfusion Injury , Lead Poisoning , Leukemia , Leukemia, Myeloid , Leukemia, Myeloid, Acute , Liver Cirrhosis , Liver Diseases , Liver Neoplasms , Liver Neoplasms, Experimental , lung cancer , Lung Diseases , Lung Injury , Lung Neoplasms , Lung Reperfusion Injury , Macular Degeneration , membranous glomerulonephritis , mental depression , Mercury Poisoning , Multiple Myeloma , Myeloproliferative Disorders , neoplasms , Neoplasms, Experimental , neurodegenerative disease , neurotoxicity syndromes , non-small cell lung carcinoma , nonalcoholic fatty liver disease , obesity , Occupational Diseases , Pancreatitis, Experimental, Chronic , papilloma , Parkinson's Disease , Poisoning , Precursor Cell Lymphoblastic Leukemia-Lymphoma , prostatic neoplasms , Prostatitis , Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Renal Fibrosis , Renal Insufficiency, Chronic , Seizures , Spinal Cord Injuries , Spinocerebellar Ataxia 17 , Status Epilepticus , Subarachnoid Hemorrhage , transient cerebral ischemia , ureteral obstruction , urinary bladder cancer , Urinary Bladder, Overactive , Urologic Neoplasms , Warfarin Sensitivity Por Adrenal Hyperplasia, Congenital , Amenorrhea , Antley-Bixler Syndrome Phenotype , Antley-Bixler Syndrome with Genital Anomalies and Disordered Steroidogenesis , ANTLEY-BIXLER SYNDROME WITHOUT GENITAL ANOMALIES OR DISORDERED STEROIDOGENESIS , Cell Transformation, Neoplastic , Gliosarcoma , Hypotension , Learning Disorders , Musculoskeletal Abnormalities , Neural Tube Defects , Pleomorphic Xanthoastrocytoma , urinary bladder cancer Ralbp1 Hypertension , Myocardial Ischemia , prostatic neoplasms , urinary bladder cancer Slc22a16 juvenile arthritis Xdh Acute Kidney Injury , Acute Lung Injury , Arterial Thrombosis , Arthritis, Experimental , Autistic Disorder , Brain Injuries , Carbon Monoxide Poisoning , Carcinoma , Carcinoma, Hepatocellular , cardiomyopathy , cardiovascular system disease , Carotid Artery Diseases , Cataract , Cholestasis , Colonic Neoplasms , diabetes mellitus, experimental , Diabetic Cardiomyopathies , Diabetic Nephropathies , Heart Diseases , Heart Failure , Hyperoxaluria , Hyperoxic Lung Injury , Hypertension , Hypertrophy, Left Ventricular , Hyperuricemia , Hypotension , Infarction, Middle Cerebral Artery , Intestinal Reperfusion Injury , Ischemia , Kidney Reperfusion Injury , Lesch-Nyhan Syndrome , Liver Neoplasms, Experimental , Liver Reperfusion Injury , major depressive disorder , Mammary Neoplasms, Animal , Mammary Neoplasms, Experimental , Multiple Organ Failure , Muscular Diseases , Myocardial Reperfusion Injury , Nephritis, Interstitial , Nephrosis, Puromycin Aminonucleoside , Nerve Degeneration , obesity , pancreatitis , Peritonitis , Pneumoperitoneum , portal hypertension , pulmonary embolism , Renal Fibrosis , Renal Insufficiency , Renal Insufficiency, Chronic , Renal Ischemia , Reperfusion Injury , Retina Reperfusion Injury , Sepsis , Shock , Spinal Cord Injuries , Testis Reperfusion Injury , Thrombocytopenia , Transplant Rejection , urinary bladder cancer , Wounds, Penetrating , xanthinuria , Xanthinuria, Type I
Abruptio Placentae Nos3 Acute Chest Syndrome Nos3 Acute Kidney Injury Nos3 , Nqo1 , Xdh Acute Lung Injury Nqo1 , Xdh acute megakaryoblastic leukemia Abcg2 adenocarcinoma Nos3 Adenoma Abcg2 Adrenal Hyperplasia, Congenital Por Adrenocortical Carcinoma Abcb1a Alopecia Abcc2 Alzheimer's Disease Nos3 Amenorrhea Por angle-closure glaucoma Nos3 Anthracycline-induced Cardiotoxicity Abcb1a Antley-Bixler Syndrome Phenotype Por Antley-Bixler Syndrome with Genital Anomalies and Disordered Steroidogenesis Por ANTLEY-BIXLER SYNDROME WITHOUT GENITAL ANOMALIES OR DISORDERED STEROIDOGENESIS Por Arterial Thrombosis Xdh Arteriosclerosis Nos3 Arteriovenous Fistula Nos3 Arthritis, Experimental Abcb1a , Abcg2 , Nos3 , Nqo1 , Xdh Arthritis, Rheumatoid Abcb1a , Abcc2 , Abcc3 , Abcg2 asthma Abcb1a , Abcc1 , Nos3 , Nqo1 atherosclerosis Nos3 Atrial Fibrillation Nos3 Autistic Disorder Xdh Behcet Syndrome Abcb1a , Nos3 bipolar disorder Ndufs7 Brain Injuries Nqo1 , Xdh Brain Ischemia Nos3 breast cancer, familial Abcc1 Breast Neoplasms Abcb1a , Abcc1 , Abcg2 , Ndufs3 , Nos3 , Nqo1 Bronchial Hyperreactivity Nos3 bronchiolitis obliterans Nos3 Carbon Monoxide Poisoning Xdh Carbon Tetrachloride Poisoning Nqo1 Carcinoma Abcb1a , Xdh Carcinoma, Ductal, Breast Abcb1a Carcinoma, Hepatocellular Abcb1a , Abcc3 , Cbr1 , Xdh Carcinoma, Intraductal, Noninfiltrating Akr1c3 Carcinoma, Renal Cell Abcb1a , Abcg2 Carcinoma, Small Cell Nqo1 Carcinoma, Squamous Cell of Head and Neck Abcb1a , Abcc1 , Abcc2 , Abcg2 Cardiomegaly Nos3 cardiomyopathy Cbr1 , Ndufs2 , Nos3 , Xdh Cardiomyopathy, Hypertrophic Ndufs2 Cardiotoxicity Nos3 cardiovascular system disease Nos3 , Xdh Carotid Artery Diseases Xdh Carotid Artery Injuries Nos3 castration-resistant prostatic neoplasms Akr1c3 Cataract Xdh Cell Transformation, Neoplastic Akr1c3 , Por Cerebral Hemorrhage Nqo1 Cerebral Infarction Nos3 Chemical and Drug Induced Liver Injury Abcb1a , Abcc1 , Abcc2 , Nqo1 Child Behavior Disorders Nos3 cholangiocarcinoma Abcc2 Cholestasis Abcc2 , Abcc3 , Nos3 , Nqo1 , Xdh Chromosome 8, Trisomy Nqo1 chronic myeloid leukemia Abcb1a , Abcc2 , Abcg2 , Nqo1 Cleft Lip Nos3 cleft palate Nos3 Colitis Nos3 Colonic Neoplasms Cbr1 , Nqo1 , Xdh Colorectal Neoplasms Abcb1a , Abcc1 , Abcc2 , Abcc3 , Abcg2 , Nqo1 Coronary Artery Disease Nos3 Coronary Vasospasm Nos3 Crohn Disease Abcb1a Cystic Fibrosis Nos3 Dermatitis, Contact Nqo1 Diabetes Mellitus Abcg2 diabetes mellitus, experimental Abcb1a , Abcc2 , Abcc3 , Abcg2 , Cbr1 , Ndufs2 , Ndufs3 , Nos3 , Nqo1 , Xdh Diabetic Angiopathies Nos3 Diabetic Cardiomyopathies Nos3 , Xdh Diabetic Gastroparesis Nos3 Diabetic Nephropathies Nos3 , Nqo1 , Xdh Diabetic Retinopathy Nos3 Disease Progression Abcb1a , Abcc1 Disorders of Sex Development Akr1c3 Drug Hypersensitivity Abcc2 drug-induced enteropathy Nos3 Drug-Induced Immune Thrombocytopenia Abcc2 Drug-induced Neutropenia Abcb1a , Abcc2 Drug-Related Side Effects and Adverse Reactions Abcb1a , Abcc1 , Abcc2 , Abcg2 Encephalitis Abcb1a Endometrial Neoplasms Akr1c3 , Nos3 Endometriosis Akr1c3 Endotoxemia Abcb1a , Abcc2 , Nos3 Eosinophilia Abcb1a Epilepsy Abcb1a Epilepsy, Familial Temporal Lobe, 3 Abcb1a Epilepsy, Temporal Lobe Abcb1a Erectile Dysfunction Nos3 Escherichia Coli Infections Abcb1a Esophageal Neoplasms Abcb1a , Nos3 esophageal squamous cell carcinoma Abcc2 essential hypertension Nos3 Fatty Liver Abcc2 , Abcc3 , Nqo1 Fetal Growth Retardation Abcb1a , Nos3 Fever Cbr1 gastric ulcer Nos3 Gastrointestinal Diseases Abcc2 Genetic Predisposition to Disease Abcb1a Glaucoma, Primary Open Angle Nos3 glioma Nos3 Gliosarcoma Por gout Abcg2 Graft Occlusion, Vascular Nos3 Guanidinoacetate Methyltransferase Deficiency Ndufs7 Hearing Loss, Sudden Nos3 Heart Defects, Congenital Abcb1a Heart Diseases Abcb1a , Abcc1 , Abcc2 , Xdh Heart Failure Nos3 , Xdh Hematologic Neoplasms Abcb1a Hemolytic-Uremic Syndrome Nqo1 Hemorrhage Nqo1 Hepatomegaly Abcc3 hepatopulmonary syndrome Nos3 Hernia, Diaphragmatic Nos3 Hernias, Diaphragmatic, Congenital Nos3 HIV Infections Abcb1a Huntington's Disease Nos3 Hyperbilirubinemia Abcc2 , Abcc3 Hyperemia Nos3 Hyperglycemia Nos3 , Nqo1 hyperinsulinism Nos3 Hyperlipidemias Abcb1a , Nos3 Hyperoxaluria Xdh Hyperoxia Nos3 , Nqo1 Hyperoxic Lung Injury Nqo1 , Xdh Hyperparathyroidism, Secondary Abcg2 Hyperprolactinemia Abcc3 Hypertension Abcc1 , Nos3 , Nqo1 , Ralbp1 , Xdh Hypertension Resistant to Conventional Therapy Nos3 Hypertension, Pregnancy-Induced Nos3 Hypertension, Renal Nos3 Hypertension, Renovascular Nos3 Hypertriglyceridemia Nos3 Hypertrophy, Left Ventricular Nos3 , Nqo1 , Xdh Hypertrophy, Right Ventricular Nos3 Hyperuricemia Abcg2 , Xdh Hypotension Por , Xdh Hypotension, Orthostatic Abcb1a Hypothyroidism Nos3 Hypoxia Nos3 Hypoxia, Brain Nos3 Infarction, Middle Cerebral Artery Nqo1 , Xdh Infertility, Male Nos3 Inflammation Abcb1a inflammatory bowel disease 13 Abcb1a inherited metabolic disorder Ndufs2 Insulin Resistance Nos3 intestinal perforation Nos3 Intestinal Polyposis Abcb1a Intestinal Reperfusion Injury Nos3 , Nqo1 , Xdh Intimal Hyperplasia Nos3 Intracranial Aneurysm Nos3 Intracranial Hemorrhages Nos3 Irritable Bowel Syndrome Nos3 irritant dermatitis Cbr1 Ischemia Nos3 , Xdh Jaundice, Chronic Idiopathic Abcc2 , Abcc3 juvenile arthritis Slc22a16 Kidney Diseases Abcb1a , Abcc3 , Nqo1 Kidney Failure, Chronic Abcb1a , Abcc2 , Abcc3 , Cbr1 , Nos3 kidney neoplasms Abcb1a Kidney Reperfusion Injury Nos3 , Nqo1 , Xdh Lead Poisoning Nqo1 Learning Disorders Por Leigh Disease Ndufs2 , Ndufs3 , Ndufs7 Leigh Syndrome Due To Mitochondrial Complex I Deficiency Ndufs3 , Ndufs7 Leiomyoma Nos3 Lesch-Nyhan Syndrome Xdh Leukemia Akr1c3 , Nqo1 Leukemia, Myeloid Nqo1 Leukemia, Myeloid, Acute Abcc3 , Abcg2 , Nos3 , Nqo1 Limb Ischemia Nos3 Liver Cirrhosis Nos3 , Nqo1 Liver Cirrhosis, Biliary Abcc2 , Abcg2 Liver Cirrhosis, Experimental Abcb1a , Abcc2 , Akr1c3 , Nos3 Liver Diseases Nqo1 Liver Failure, Acute Abcc2 , Nos3 Liver Injury Abcg2 Liver Neoplasms Nqo1 Liver Neoplasms, Experimental Nqo1 , Xdh Liver Reperfusion Injury Nos3 , Xdh lung cancer Nqo1 Lung Diseases Nos3 , Nqo1 Lung Injury Nqo1 Lung Neoplasms Nqo1 Lung Reperfusion Injury Nos3 , Nqo1 lymphangioleiomyomatosis Nos3 Lymphatic Metastasis Nos3 lymphocytic leukemia, chronic, B-cell Abcg2 Lymphoma, B-Cell Abcg2 Lymphoma, Extranodal NK-T-Cell Abcb1a Lymphoma, Large B-Cell, Diffuse Abcb1a , Abcg2 Macular Degeneration Nqo1 macular retinal edema Nos3 major depressive disorder Xdh Mammary Neoplasms, Animal Xdh Mammary Neoplasms, Experimental Abcb1a , Abcg2 , Xdh marijuana abuse Abcb1a membranous glomerulonephritis Nqo1 mental depression Nqo1 Mental Disorders Abcb1a Mercury Poisoning Nqo1 Metabolic Syndrome X Nos3 Migraine Disorders Nos3 Mitochondrial Complex I Deficiency Ndufs2 , Ndufs3 , Ndufs7 Mitochondrial Encephalomyopathies Ndufs2 Mouth Neoplasms Cbr3 Multiple Myeloma Abcg2 , Nqo1 Multiple Organ Failure Xdh Multiple Sclerosis Ndufs2 Muscular Diseases Xdh Musculoskeletal Abnormalities Por Myeloproliferative Disorders Akr1c3 , Nqo1 Myocardial Infarction Nos3 Myocardial Ischemia Nos3 , Ralbp1 Myocardial Reperfusion Injury Nos3 , Xdh Nasal Polyps Abcb1a , Nos3 Nausea Abcb1a necrotizing enterocolitis Abcb1a , Akr1a1 , Nos3 Neoplasm Metastasis Abcb1a , Nos3 neoplasms Abcb1a , Nos3 , Nqo1 Neoplasms, Experimental Nqo1 Neoplasms, Germ Cell and Embryonal Abcb1a Neoplasms, Hormone-Dependent Akr1c3 Nephritis Nos3 Nephritis, Interstitial Xdh Nephrosis, Puromycin Aminonucleoside Xdh Nerve Degeneration Xdh Nervous System Diseases Abcb1a , Abcc2 , Abcg2 Neural Tube Defects Por neuroblastoma Abcb1a neurodegenerative disease Nqo1 neurotoxicity syndromes Abcb1a , Abcg2 , Nqo1 Neutropenia Abcb1a non-small cell lung carcinoma Abcb1a , Abcc2 , Nqo1 nonalcoholic fatty liver disease Abcb1a , Abcc3 , Nqo1 obesity Akr1c3 , Nos3 , Nqo1 , Xdh Occupational Diseases Nqo1 Optic Atrophy Ndufs3 Optic Neuropathy, Ischemic Nos3 Ovarian Neoplasms Abcb1a , Abcg2 , Nos3 overnutrition Nos3 Pain Abcb1a , Nos3 Pain, Postoperative Abcb1a Pancreatic Neoplasms Abcc2 , Abcc3 pancreatitis Xdh Pancreatitis, Experimental, Chronic Nqo1 papilloma Nqo1 Parkinson's Disease Abcb1a , Nqo1 Parkinson's Disease, Secondary Abcb1a perennial allergic rhinitis Nos3 Peripheral Nervous System Diseases Abcb1a , Abcc1 Peritonitis Xdh Phyllodes Tumor Nos3 Pleomorphic Xanthoastrocytoma Abcb1a , Por Pneumonia, Bacterial Abcc1 Pneumoperitoneum Xdh Poisoning Abcb1a , Nqo1 Polycystic Kidney Diseases Nos3 Polycystic Ovary Syndrome Akr1c3 portal hypertension Nos3 , Xdh Pre-Eclampsia Akr1c3 , Nos3 Precursor B-Cell Lymphoblastic Leukemia-Lymphoma Akr1c3 Precursor Cell Lymphoblastic Leukemia-Lymphoma Abcb1a , Abcc2 , Abcg2 , Nos3 , Nqo1 Precursor T-Cell Lymphoblastic Leukemia-Lymphoma Abcg2 , Akr1c3 prostate cancer Akr1c3 prostatic neoplasms Akr1c3 , Cbr1 , Nos3 , Nqo1 , Ralbp1 Prostatitis Nqo1 Pseudoxanthoma Elasticum Abcc1 Pulmonary Disease, Chronic Obstructive Abcc1 , Nos3 , Nqo1 Pulmonary Edema Nos3 pulmonary embolism Nos3 , Xdh Pulmonary Emphysema Nos3 , Nqo1 pulmonary eosinophilia Nos3 pulmonary hypertension Nos3 Pulmonary Hypertension, Hypoxia-Induced Nos3 Radiation Pneumonitis Nos3 Renal Fibrosis Nqo1 , Xdh Renal Insufficiency Xdh Renal Insufficiency, Chronic Cbr1 , Nos3 , Nqo1 , Xdh Renal Ischemia Xdh Reperfusion Injury Abcb1a , Abcg2 , Nos3 , Xdh Respiratory Hypersensitivity Nos3 Retina Reperfusion Injury Nos3 , Xdh Retinal Degeneration Nos3 Retinopathy of Prematurity Nos3 Rhinitis, Allergic Abcb1a Schizophrenia Abcc1 Seizures Abcb1a , Abcc2 , Nqo1 Sepsis Nos3 , Xdh Shock Xdh Shock, Hemorrhagic Nos3 sickle cell anemia Nos3 Sleep Apnea, Central Nos3 Sleep Apnea, Obstructive Abcb1a , Nos3 Smith-Magenis syndrome Abcc3 Spinal Cord Compression Nos3 Spinal Cord Injuries Nos3 , Nqo1 , Xdh Spinocerebellar Ataxia 17 Nqo1 Status Epilepticus Abcb1a , Abcc2 , Abcg2 , Nqo1 Stomach Neoplasms Akr1c3 , Nos3 Stroke Nos3 Subarachnoid Hemorrhage Nos3 , Nqo1 Tachycardia, Ventricular Nos3 Telangiectasis Nos3 Testis Reperfusion Injury Nos3 , Xdh Thrombocytopenia Xdh Thromboembolism Nos3 Thrombotic Microangiopathies Nos3 transient cerebral ischemia Nos3 , Nqo1 Translocation, Genetic Abcb1a Transplant Rejection Nos3 , Xdh type 1 diabetes mellitus Nos3 type 2 diabetes mellitus Abcb1a , Abcc2 , Nos3 Uremia Nos3 ureteral obstruction Nos3 , Nqo1 URIC ACID CONCENTRATION, SERUM, QUANTITATIVE TRAIT LOCUS 1 Abcg2 urinary bladder cancer Nos3 , Nqo1 , Por , Ralbp1 , Xdh urinary bladder neck obstruction Nos3 Urinary Bladder, Overactive Nqo1 Urologic Neoplasms Nqo1 Vasculitis Nos3 Vaso-occlusive Crisis Nos3 Venous Thrombosis Nos3 Ventricular Dysfunction, Right Nos3 Ventricular Premature Complexes Nos3 Vestibular Diseases Nos3 Vomiting Abcb1a Vulvar Neoplasms Nos3 Warfarin Sensitivity Nqo1 Wet Macular Degeneration Nos3 Wilms tumor Abcb1a Wounds, Penetrating Xdh xanthinuria Xdh Xanthinuria, Type I Xdh