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Mammalian de novo pyrimidine biosynthesis is accomplished by six enzymatic activities, encoded by only three genes - two encode multifunctional proteins. In the de novo synthesis of pyrimidines, the pyrimidine ring is added to the ribose-5-phosphate after the ring has been generated, unlike purines. The first reaction of the six-step pathway to generate uridine monophosphate (UMP) is catalyzed by the carbamoyl phosphate synthetase II activity of the trifunctional cytosolic mammalian enzyme Cad,

Pathway Diagram:

Ariadne Genomics Inc. deoxyribonucleotide metabolic pathway nucleotide sugar biosynthetic pathway Nme members hexosamine biosynthetic pathway transcription pathway phosphatidylcholine biosynthetic pathway ATP ADP UTP UDP UMP PRPP CTP CDP CTP ---> CDP UDP ---> UTP Cmpk1 UMP ---> UDP Cmpk2 Ctps2 Ctps PRPP --+> Umps Umps orotidine-5'-P ---> CO2 CO2 orotidine-5'-P ---> UMP PRPP ---> PPi PPi orotate ---> orotidine-5'-P ubiquinone ---> ubiquinol ubiquinol ubiquinone dihydroorotate ---> orotate HCO3- L-glutamate ureidosuccinate ---> H2O H2O ureidosuccinate ---> dihydroorotate Pi Sspartate L-glutamine ---> carbamoyl-P L-glutamine ATP ---> L-glutamate ATP ---> ADP HCO3- ---> ADP carbamoyl-P ---> ureidosuccinate Sspartate ---> Pi UDP ---> deoxyribonucleotide metabolic pathway CDP ---> deoxyribonucleotide metabolic pathway UTP ---> nucleotide sugar biosynthetic pathway CTP ---> transcription pathway UTP ---> transcription pathway CTP ---> phosphatidylcholine biosynthetic pathway UTP ---> hexosamine biosynthetic pathway orotidine-5'-P orotate dihydroorotate ureidosuccinate carbamoyl-P ATP --+> Cad PRPP --+> Cad UMP ---| Umps UDP ---| Cad UTP ---| Cad UTP ---> CTP Dhodh Cad

Genes in Pathway:

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de novo pyrimidine biosynthetic pathway term browser
Symbol Object Name JBrowse Chr Start Stop Reference
G Cad carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase JBrowse link 6 26,657,507 26,680,459 RGD:5133412
G Cmpk1 cytidine/uridine monophosphate kinase 1 JBrowse link 5 133,759,722 133,786,452 RGD:5133414
G Cmpk2 cytidine/uridine monophosphate kinase 2 JBrowse link 6 45,683,242 45,694,824 RGD:5133256
G Ctps1 CTP synthase 1 JBrowse link 5 139,475,934 139,505,065 RGD:5133414
G Ctps2 CTP synthase 2 JBrowse link X 33,383,087 33,522,852 RGD:5133419
G Dhodh dihydroorotate dehydrogenase (quinone) JBrowse link 19 42,066,103 42,087,906 RGD:5133412
G Nme1 NME/NM23 nucleoside diphosphate kinase 1 JBrowse link 10 81,657,152 81,666,542 RGD:5134680
G Nme2 NME/NM23 nucleoside diphosphate kinase 2 JBrowse link 10 81,648,216 81,653,717 RGD:5134680
G Nme3 NME/NM23 nucleoside diphosphate kinase 3 JBrowse link 10 14,258,232 14,259,365 RGD:5134680
G Nme4 NME/NM23 nucleoside diphosphate kinase 4 JBrowse link 10 15,461,567 15,465,422 RGD:5134680
G Nme6 NME/NM23 nucleoside diphosphate kinase 6 JBrowse link 8 117,920,912 117,928,148 RGD:5134680
G Umps uridine monophosphate synthetase JBrowse link 11 70,034,181 70,044,590 RGD:5133412

Additional Elements in Pathway:

(includes Gene Groups, Small Molecules, Other Pathways..etc.)
Object TypePathway ObjectPathway Object Description
Small MoleculeADPadenosine diphosphate
Small MoleculeATPadenosine triphosphate
Small MoleculeCDPcytidine diphosphate
Small MoleculeCTPcytidine triphosphate
Functional ClassNme membersmembers of the nucleoside diphosphate kinase family
Small MoleculePRPPphosphoribosyl pyrophosphate
Small MoleculeUDPuridine diphosphate
Small MoleculeUMPuridine monophosphate
Small MoleculeUTPuridine triphosphate

Pathway Gene Annotations

Disease Annotations Associated with Genes in the de novo pyrimidine biosynthetic pathway
Disease TermsGene Symbols
Acute Erythroblastic LeukemiaCad , Dhodh , Umps
autistic disorderCtps2
beta thalassemiaCad , Dhodh , Umps
biliary tract benign neoplasmCtps1
breast cancerNme1
breast carcinomaNme1
Breast NeoplasmsUmps
Charcot-Marie-Tooth disease dominant intermediate CCtps1
Chemical and Drug Induced Liver InjuryNme2
Colonic NeoplasmsUmps
colorectal cancerCtps2
Colorectal NeoplasmsNme1 , Nme2 , Umps
congenital hypoplastic anemiaCad , Umps
congestive heart failureNme2
Diabetes Mellitus, Experimental Cad , Dhodh , Umps
early infantile epileptic encephalopathy 50Cad
Experimental ArthritisDhodh
Experimental Autoimmune NeuritisDhodh
Experimental Liver NeoplasmsCad , Dhodh
Fetal Growth RetardationCad
Genee-Wiedemann SyndromeDhodh
Germ Cell and Embryonal NeoplasmsNme2
hepatocellular carcinomaCad , Nme1 , Umps
hereditary spherocytosisCad , Dhodh , Umps
hypertrophic cardiomyopathyNme1
Immediate HypersensitivityDhodh
Lymphatic MetastasisNme1 , Nme2
Mammary Neoplasms, ExperimentalCad
Mouth NeoplasmsUmps
multiple sclerosisCmpk2
Nasopharyngeal NeoplasmsCtps1
Neoplasm InvasivenessNme1
Neoplasm MetastasisNme1 , Nme2
non-small cell lung carcinomaCmpk1
orotic aciduriaUmps
Orotic Aciduria IIUmps
ovarian cancerNme1 , Nme2
ovarian carcinomaNme2
Ovarian NeoplasmsNme2
ovary epithelial cancerNme1
pancreatic ductal carcinomaNme1
prostate carcinomaNme1
prostatic hypertrophyNme2
Prostatic NeoplasmsUmps
purine-pyrimidine metabolic disorderUmps
renal cell carcinomaNme1
sickle cell anemiaCad , Dhodh , Umps
Skin NeoplasmsNme2
squamous cell carcinomaNme1 , Umps
Stomach NeoplasmsUmps
teratomaNme1 , Nme2
Transplant RejectionDhodh
urinary bladder cancerNme1 , Nme2
Pathway Annotations Associated with Genes in the de novo pyrimidine biosynthetic pathway
Pathway TermsGene Symbols
2-hydroxyglutaric aciduria pathwayCad
adefovir pharmacokinetics pathwayNme1 , Nme2
adenine phoshoribosyltransferase deficiency pathwayNme6
adenosine monophosphate deaminase deficiency pathwayNme6
adenylosuccinate lyase deficiency pathwayNme6
AICA-ribosuria pathwayNme6
alanine, aspartate and glutamate metabolic pathwayCad
azathioprine pharmacodynamics pathwayNme6
beta-ureidopropionase deficiency pathwayCad , Cmpk2 , Ctps1 , Dhodh , Nme6 , Umps
Canavan disease pathwayCad
cardiolipin metabolic pathwayNme4
de novo pyrimidine biosynthetic pathwayCad , Cmpk1 , Cmpk2 , Ctps1 , Ctps2 , Dhodh , Nme1 , Nme2 , Nme3 , Nme4 , Nme6 , Umps
dihydropyrimidinase deficiency pathwayCad , Cmpk2 , Ctps1 , Dhodh , Nme6 , Umps
E-cadherin signaling pathwayNme1
gemcitabine pharmacodynamics pathwayCmpk1 , Ctps1 , Nme1
gemcitabine pharmacokinetics pathwayCmpk1 , Ctps1 , Nme1
Glut1 deficiency syndrome pathwayCmpk1 , Nme2
glutamic acid/glutamate metabolic pathwayCad
homocarnosinosis pathwayCad
Kelley-Seegmiller syndrome pathwayNme6
lactose biosynthetic pathwayCmpk1 , Nme2
lamivudine pharmacokinetics pathwayCmpk1 , Nme1
Lesch-Nyhan syndrome pathwayNme6
mercaptopurine pharmacodynamics pathwayNme6
mitochondrial neurogastrointestinal encephalopathy syndrome pathwayCad , Cmpk2 , Ctps1 , Dhodh , Nme6 , Umps
molybdenum cofactor deficiency pathwayNme6
orotic aciduria 1 pathwayCad , Cmpk2 , Ctps1 , Dhodh , Nme6 , Umps
purine metabolic pathwayNme1 , Nme2 , Nme3 , Nme4 , Nme6
purine nucleoside phosphorylase deficiency pathwayNme6
pyrimidine metabolic pathwayCad , Cmpk1 , Cmpk2 , Ctps1 , Ctps2 , Dhodh , Nme1 , Nme2 , Nme3 , Nme4 , Nme6 , Umps
succinic semialdehyde dehydrogenase deficiency pathwayCad
tenofovir pharmacokinetics pathwayNme1 , Nme2
tioguanine pharmacodynamics pathwayNme6
xanthinuria type I pathwayNme6
xanthinuria pathwayNme6
xanthinuria type II pathwayNme6
Phenotype Annotations Associated with Genes in the de novo pyrimidine biosynthetic pathway
Phenotype TermsGene Symbols
decreased metastatic potentialNme2

References Associated with the de novo pyrimidine biosynthetic pathway:

Ontology Path Diagram:

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