WordNet
- the organic processes (in a cell or organism) that are necessary for life (同)metabolic_process
- a heterocyclic organic compound with a penetrating odor
- any of several basic compounds derived from pyrimidine
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- 新陳代謝,物質交代
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出典(authority):フリー百科事典『ウィキペディア(Wikipedia)』「2015/05/23 23:40:20」(JST)
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Pyrimidine biosynthesis occurs both in the body and through organic synthesis.
Contents
- 1 De novo biosynthesis of pyrimidine
- 2 Pyrimidine catabolism
- 3 Pharmacotherapy
- 4 References
- 5 External links
De novo biosynthesis of pyrimidine
carbamoyl phosphate synthetase II[1] |
carbamoyl phosphate |
This is the regulated step in the pyrimidine biosynthesis. |
aspartic transcarbamolyase (aspartate carbamoyl transferase)[1] |
carbamoyl aspartic acid |
- |
dihhydroorotase[1] |
dihydroorotate |
Dehydration |
dihydroorotate dehydrogenase[2] (the only mitochondrial enzyme) |
orotate |
Dihydroorotate then enters the mitochondria where it is oxidised through removal of hydrogens. This is the only mitochondrial step in nucleotide rings biosynthesis. |
orotate phosphoribosyltransferase[3] |
OMP |
PRPP is used. |
OMP decarboxylase[3] |
UMP |
Decarboxylation |
uridine-cytidine kinase 2[4] |
UDP |
Phosphorylation. ATP is used. |
nucleoside diphosphate kinase |
UTP |
Phosphorylation. ATP is used. |
CTP synthase |
CTP |
Glutamine and ATP are used. |
The first three enzymes are all coded by the same gene in Metazoa (CAD). In Fungi, a similar protein exists but lacks the dihydroorotase function: another protein catalyzes the second step.
In other organisms (Bacteria, Archaea and the other Eukaryota), the first three steps are done by three different enzymes.
Pyrimidine catabolism
Pyrimidines are ultimately catabolized (degraded) to CO2, H2O, and urea. Cytosine can be broken down to uracil, which can be further broken down to N-carbamoyl-β-alanine, and then to beta-alanine, CO2, and ammonia by beta-ureidopropionase. Thymine is broken down into β-aminoisobutyrate which can be further broken down into intermediates eventually leading into the citric acid cycle.
β-aminoisobutyrate acts as a rough indicator for rate of DNA turnover.[5]
Pharmacotherapy
Modulating the pyrimidine metabolism pharmacologically has therapeutical uses.
Pyrimidine synthesis inhibitors are used in active moderate to severe rheumatoid arthritis and psoriatic arthritis. Examples include Leflunomide and Teriflunomide.
References
- ^ a b c "Entrez Gene: CAD carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase".
- ^ "Entrez Gene: DHODH dihydroorotate dehydrogenase".
- ^ a b "Entrez Gene: UMPS uridine monophosphate synthetase".
- ^ "Entrez Gene: UCK2 uridine-cytidine kinase 2".
- ^ Nielsen, HR; Sjolin, KE; Nyholm, K; Baliga, BS; Wong, R; Borek, E (1974). "Beta-aminoisobutyric acid, a new probe for the metabolism of DNA and RNA in normal and tumorous tissue". Cancer research 34 (6): 1381–4. PMID 4363656.
External links
- Overview at Queen Mary, University of London
Metabolism map
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Cellulose and sucrose
metabolism
Starch and glycogen
metabolism
Pentose phosphate pathway
Glycolysis and Gluconeogenesis
Small amino acid synthesis
Branched amino acid
synthesis
Aromatic amino
acid synthesis
Aspartate amino acid
group synthesis
Porphyrins and
corrinoids
metabolism
Glutamate amino
acid group
synthesis
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All pathway labels on this image are links, simply click to access the article. |
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A high resolution labeled version of this image is available here. |
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Metabolism catabolism, anabolism
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General |
- Metabolic pathway
- Metabolic network
- Primary nutritional groups
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Energy
metabolism |
Aerobic respiration |
- Glycolysis → Pyruvate decarboxylation → Citric acid cycle → Oxidative phosphorylation (electron transport chain + ATP synthase)
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Anaerobic respiration |
- Electron acceptors are other than oxygen
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Fermentation |
- Glycolysis →
- Substrate-level phosphorylation
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Specific
paths |
Protein metabolism |
- Protein synthesis
- Catabolism
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Carbohydrate metabolism
(carbohydrate catabolism
and anabolism) |
Human |
- Glycolysis ⇄ Gluconeogenesis
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- Glycogenolysis ⇄ Glycogenesis
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- Pentose phosphate pathway
- Fructolysis
- Galactolysis
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Nonhuman |
- Photosynthesis
- Anoxygenic photosynthesis
- Chemosynthesis
- Carbon fixation
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- Xylose metabolism
- Radiotrophism
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Lipid metabolism
(lipolysis, lipogenesis) |
Fatty acid metabolism |
- Fatty acid degradation (Beta oxidation)
- Fatty acid synthesis
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Other |
- Steroid metabolism
- Sphingolipid metabolism
- Eicosanoid metabolism
- Ketosis
- Reverse cholesterol transport
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Amino acid |
- Amino acid synthesis
- Urea cycle
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Nucleotide
metabolism |
- Purine metabolism
- Nucleotide salvage
- Pyrimidine metabolism
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Other |
- Metal metabolism
- Ethanol metabolism
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Index of inborn errors of metabolism
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Description |
- Metabolism
- Enzymes and pathways: citric acid cycle
- pentose phosphate
- glycoproteins
- glycosaminoglycans
- phospholipid
- cholesterol and steroid
- sphingolipids
- eicosanoids
- amino acid
- urea cycle
- nucleotide
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Disorders |
- Citric acid cycle and electron transport chain
- Glycoprotein
- Proteoglycan
- Fatty-acid
- Phospholipid
- Cholesterol and steroid
- Eicosanoid
- Amino acid
- Purine-pyrimidine
- Heme metabolism
- Symptoms and signs
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Treatment |
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Index of biochemical families
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Carbohydrates |
- Alcohols
- Glycoproteins
- Glycosides
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Lipids |
- Eicosanoids
- Fatty acids
- Glycerides
- Phospholipids
- Sphingolipids
- Steroids
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Nucleic acids |
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Proteins |
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Other |
- Tetrapyrroles
- intermediates
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- Metabolism: amino acid metabolism
- nucleotide enzymes
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Purine metabolism |
Anabolism |
R5P→IMP: |
- Ribose-phosphate diphosphokinase
- Amidophosphoribosyltransferase
- Phosphoribosylglycinamide formyltransferase
- AIR synthetase (FGAM cyclase)
- Phosphoribosylaminoimidazole carboxylase
- Phosphoribosylaminoimidazolesuccinocarboxamide synthase
- IMP synthase
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IMP→AMP: |
- Adenylosuccinate synthase
- Adenylosuccinate lyase
- reverse
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IMP→GMP: |
- IMP dehydrogenase
- GMP synthase
- reverse
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Nucleotide salvage |
- Hypoxanthine-guanine phosphoribosyltransferase
- Adenine phosphoribosyltransferase
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Catabolism |
- Adenosine deaminase
- Purine nucleoside phosphorylase
- Guanine deaminase
- Xanthine oxidase
- Urate oxidase
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Pyrimidine metabolism |
Anabolism |
- CAD
- Carbamoyl phosphate synthase II
- Aspartate carbamoyltransferase
- Dihydroorotase
|
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- Dihydroorotate dehydrogenase
- Orotidine 5'-phosphate decarboxylase/Uridine monophosphate synthetase
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Catabolism |
- Dihydropyrimidine dehydrogenase
- Dihydropyrimidinase/DPYS
- Beta-ureidopropionase/UPB1
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Deoxyribonucleotides |
- Ribonucleotide reductase
- Nucleoside-diphosphate kinase
- DCMP deaminase
- Thymidylate synthase
- Dihydrofolate reductase
|
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Index of inborn errors of metabolism
|
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Description |
- Metabolism
- Enzymes and pathways: citric acid cycle
- pentose phosphate
- glycoproteins
- glycosaminoglycans
- phospholipid
- cholesterol and steroid
- sphingolipids
- eicosanoids
- amino acid
- urea cycle
- nucleotide
|
|
Disorders |
- Citric acid cycle and electron transport chain
- Glycoprotein
- Proteoglycan
- Fatty-acid
- Phospholipid
- Cholesterol and steroid
- Eicosanoid
- Amino acid
- Purine-pyrimidine
- Heme metabolism
- Symptoms and signs
|
|
Treatment |
|
|
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UpToDate Contents
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English Journal
- Involvement of enhancer of zeste homolog 2 in cisplatin‑resistance in ovarian cancer cells by interacting with several genes.
- Wang H1, Yu Y1, Chen C1, Wang Q1, Huang T1, Hong F2, Zhu L1.
- Molecular medicine reports.Mol Med Rep.2015 Aug;12(2):2503-10. doi: 10.3892/mmr.2015.3745. Epub 2015 May 7.
- In the present study, gene expression profiles of cisplatin‑sensitive ovarian cancer (OC) cells were compared with those of cisplatin‑resistant OC cells to identify key genes and pathways contributing to cisplatin resistance in ovarian cancer cells. The GSE15372 gene expression data set was down
- PMID 25955318
- Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma.
- Makinoshima H1, Takita M2, Saruwatari K3, Umemura S3, Obata Y4, Ishii G5, Matsumoto S6, Sugiyama E3, Ochiai A5, Abe R4, Goto K3, Esumi H7, Tsuchihara K2.
- The Journal of biological chemistry.J Biol Chem.2015 Jul 10;290(28):17495-504. doi: 10.1074/jbc.M115.660498. Epub 2015 May 28.
- Oncogenic epidermal growth factor receptor (EGFR) signaling plays an important role in regulating global metabolic pathways, including aerobic glycolysis, the pentose phosphate pathway (PPP), and pyrimidine biosynthesis. However, the molecular mechanism by which EGFR signaling regulates cancer cell
- PMID 26023239
Japanese Journal
- CYP-dependent Metabolism of Antitumor Pyrazolo[3,4-d]pyrimidine Derivatives Is Characterized by an Oxidative Dechlorination Reaction
- , , , , , , , , ,
- Drug Metabolism
- … In HLM, the dehalogenated metabolite accounts for about 87% of the full 1 metabolism, while the N-dealkylated metabolite accounts for 12%. … Inhibition studies performed using different CYP-inhibitors indicate that the 3A family is the isoenzyme family most involved in pyrazolo[3,4-d]pyrimidine metabolism. …
- NAID 130004933549
- Synthesis and Biological Evaluation of 3-Methyl-5-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione Derivatives for the Treatment of Diet-Induced Obesity
- , , , , , , , , , , , , , , , ,
- Chemical and Pharmaceutical Bulletin 62(9), 883-891, 2014
- … Triglycerides are the main part of fats and half of the lipids in hepatocytes, and play an important role in metabolism as energy sources and transporters of dietary fat. … In this study, 33 derivatives based on 3-methyl-5-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione were synthesized and evaluated for their lipid-lowering activity. …
- NAID 130004684769
Related Links
- Pyrimidine metabolism - Reference pathway [ Pathway menu | Organism menu | Pathway entry | User data mapping]
- Purine and Pyrimidine Nucleotide Biosynthesis, Purine and Pyrimidine synthesis pathway made easy!, PURINE AND PYRIMIDINE SYNTHESIS PART 1, PURINE AND PYRIMIDINE SYNTHESIS PART 2, 141-Pyrimidine Synthesis ...
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先天性プリン・ピリミジン代謝異常、先天性核酸代謝異常