Pyrimidine metabolism (Homo sapiens)
From WikiPathways
Description
Pyrimidines are nucleic acids and the products of pyrimidine degradation are water-soluble. The pyrimidine ring is synthesized before it is conjugated to PRPP. The first reaction is the conjugation of carbamoyl phosphate and aspartate to make N-carbamoylaspartate. The carbamoyl phosphate synthetase used in pyrimidine biosynthesis is located in the cytoplasm. The enzyme that carries out the reaction is aspartate transcarbamoylase, an enzyme that is closely regulated. The second reaction is ring closure to form dihydroorotic acid by the enzyme dihydroorotase. This circular product contains a 6-membered ring with nitrogen and carbons located in the same positions as in the mature pyrimidine ring. The third reaction is the oxidation of the ring to form a carbon- carbon bond. The reducing equivalents are transferred to a flavin cofactor of the enzyme dihydroorotate dehydrogenase. The product is orotic acid. Fourth, the orotate ring is transferred to phosphoribosyl pyrophosphate (PRPP) to form a 5-ribose-phosphate, orotidylic acid. Finally orotidylate is decarboxylated to yield UMP, which of course contains one of the bases of RNA. Cellular kinases convert UMP to UTP. Transfer of an amido nitrogen from glutamine by CTP synthetase converts UTP to CTP; this reaction uses an ATP high-energy phosphate. Pyrimidine synthesis is controlled at the first committed step. ATP stimulates the aspartate transcarbamoylase reaction, while CTP inhibits it. CTP is a feedback inhibitor of the pathway, and ATP is a feed-forward activator. This regulation ensures that a balanced supply of purines and pyrimidines exists for RNA and synthesis.
Eukaryotic organisms contain a multifunctional enzyme with carbamoylphosphate synthetase, aspartate transcarbamoylase, and dihydroorotase activities. Two mechanisms control this enzyme. First, control at the level of enzyme synthesis exists; the transcription of the gene for the enzyme is reduced if an excess of pyrimidines is present. Secondly, control exists at the level of feedback inhibition by pyrimidine nucleotides. This enzyme is also an example of the phenomenon of metabolic channeling: aspartate, ammonia, and carbon dioxide enter the enzyme and come out as orotic acid
Description text is based on Cliff's Notes.
Pathway is based on KEGG
Proteins on this pathway have targeted assays available via the CPTAC Assay PortalQuality Tags
Ontology Terms
Bibliography
- ''''; https://www.genome.jp/dbget-bin/www_bget?pathway+map00240,
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
(R)-3-aminoisobutyrate | Metabolite | C01205 (KEGG Compound) | |
(R)-3-ureidoisobutyrate | Metabolite | C21029 (KEGG Compound) | |
(R)-dihydrothymine | Metabolite | C21028 (KEGG Compound) | |
2-deoxy-D-ribose-1P | Metabolite | 439287 (PubChem-compound) | |
3-Ureidopropionate | Metabolite | C02642 (KEGG Compound) | |
5,6-Dihydrouracil | Metabolite | C00429 (KEGG Compound) | |
AK9 | GeneProduct | NP_001138600 (NCBI Protein) | Check literature for directionality of enzyme |
Alanine, aspartate and glutamate metabolism | Pathway | http://www.kegg.jp/dbget-bin/www_bget?mtu00250 | |
Arginine and proline metabolism | Pathway | http://www.kegg.jp/dbget-bin/www_bget?mtu00330 | |
CAD | GeneProduct | 790 (Entrez Gene) | Original kegg element: gene;15;mtu:Rv1381 |
CANT1 | GeneProduct | NP_001153244 (NCBI Protein) | Original kegg element: gene;111;mtu:Rv1021 |
CDA | GeneProduct | 978 (Entrez Gene) | Original kegg element: gene;48;mtu:Rv3315c |
CDP | Metabolite | C00112 (KEGG Compound) | |
CMP | Metabolite | HMDB0000095 (HMDB) | |
CMPK1 | GeneProduct | 51727 (Entrez Gene) | Original kegg element: gene;4;mtu:Rv2883c |
CMPK2 | GeneProduct | 129607 (Entrez Gene) | Original kegg element: gene;4;mtu:Rv2883c |
CTP | Metabolite | C00063 (KEGG Compound) | |
CTPS1 | GeneProduct | 1503 (Entrez Gene) | Original kegg element: gene;25;mtu:Rv0321 |
CTPS2 | GeneProduct | 56474 (Entrez Gene) | Original kegg element: gene;25;mtu:Rv0321 |
Carbamoylphosphate | Metabolite | HMDB0001096 (HMDB) | |
Cytidine | Metabolite | HMDB0000089 (HMDB) | |
DCK | GeneProduct | 1633 (Entrez Gene) | |
DCTD | GeneProduct | 1635 (Entrez Gene) | |
DCTPP1 | GeneProduct | 79077 (Entrez Gene) | |
DHODH | GeneProduct | 1723 (Entrez Gene) | Original kegg element: gene;17;mtu:Rv2139 |
DNA | Metabolite | C00039 (KEGG Compound) | |
DPYD | GeneProduct | 1806 (Entrez Gene) | |
DPYS | GeneProduct | 1807 (Entrez Gene) | |
DPYS | GeneProduct | NP_001376 (NCBI Protein) | |
DTYMK | GeneProduct | 1841 (Entrez Gene) | Original kegg element: gene;85;mtu:Rv3247c |
DUT | GeneProduct | 1854 (Entrez Gene) | Original kegg element: gene;70;mtu:Rv2697c |
Deoxycytidine | Metabolite | C00881 (KEGG Compound) | |
Deoxyuridine | Metabolite | HMDB0000012 (HMDB) | |
Dihydroorotate | Metabolite | HMDB0003349 (HMDB) | |
Diphosphate | Metabolite | CHEBI:45212 (ChEBI) | |
ENPP1 | GeneProduct | 5167 (Entrez Gene) | Original kegg element: gene;26;mtu:Rv1699 |
ENPP3 | GeneProduct | 5169 (Entrez Gene) | Original kegg element: gene;26;mtu:Rv1699 |
ENTPD1 | GeneProduct | 953 (Entrez Gene) | |
ENTPD1 | GeneProduct | NP_001767 (NCBI Protein) | |
ENTPD3 | GeneProduct | 956 (Entrez Gene) | |
ENTPD3 | GeneProduct | NP_001239 (NCBI Protein) | |
ENTPD4 | GeneProduct | NP_004892 (NCBI Protein) | Original kegg element: gene;111;mtu:Rv1021 |
ENTPD5 | GeneProduct | NP_001240 (NCBI Protein) | Original kegg element: gene;111;mtu:Rv1021 |
ENTPD6 | GeneProduct | NP_001238 (NCBI Protein) | Original kegg element: gene;111;mtu:Rv1021 |
ENTPD8 | GeneProduct | NP_001028285 (NCBI Protein) | |
L-Glutamine | Metabolite | HMDB0000641 (HMDB) | |
N-Carbamoylaspartate | Metabolite | HMDB0000828 (HMDB) | |
NME1-NME2 | GeneProduct | 654364 (Entrez Gene) | |
NME1 | GeneProduct | 4830 (Entrez Gene) | |
NME | GeneProduct | 2.7.4.6 (Enzyme Nomenclature) | |
NME2 | GeneProduct | 4831 (Entrez Gene) | |
NME3 | GeneProduct | 4832 (Entrez Gene) | |
NME4 | GeneProduct | 4833 (Entrez Gene) | |
NME6 | GeneProduct | 10201 (Entrez Gene) | |
NME7 | GeneProduct | 29922 (Entrez Gene) | |
NT5C | GeneProduct | 30833 (Entrez Gene) | |
NT5E | GeneProduct | NP_002517 (NCBI Protein) | |
NT5M | GeneProduct | 56953 (Entrez Gene) | |
NUDT2 | GeneProduct | NP_001152 (NCBI Protein) | |
Orotate | Metabolite | C00295 (KEGG Compound) | |
Orotidine 5'-phosphate | Metabolite | C01103 (KEGG Compound) | |
PNP | GeneProduct | NP_000261 (NCBI Protein) | |
PNPT1 | GeneProduct | 87178 (Entrez Gene) | Original kegg element: gene;41;mtu:Rv2783c |
PNPT1 | GeneProduct | NP_149100 (NCBI Protein) | |
POLA1 | GeneProduct | 5422 (Entrez Gene) | |
POLA2 | GeneProduct | 23649 (Entrez Gene) | |
POLD1 | GeneProduct | 5424 (Entrez Gene) | |
POLD2 | GeneProduct | 5425 (Entrez Gene) | |
POLD3 | GeneProduct | 10714 (Entrez Gene) | |
POLD4 | GeneProduct | 57804 (Entrez Gene) | |
POLE1 | GeneProduct | 5426 (Entrez Gene) | |
POLE2 | GeneProduct | 5427 (Entrez Gene) | |
POLE3 | GeneProduct | 54107 (Entrez Gene) | |
POLE4 | GeneProduct | 56655 (Entrez Gene) | |
POLR1A | GeneProduct | 25885 (Entrez Gene) | |
POLR1B | GeneProduct | 84172 (Entrez Gene) | |
POLR1C | GeneProduct | 9533 (Entrez Gene) | |
POLR1D | GeneProduct | 51082 (Entrez Gene) | |
POLR1E | GeneProduct | 64425 (Entrez Gene) | |
POLR2A | GeneProduct | 5430 (Entrez Gene) | |
POLR2B | GeneProduct | 5431 (Entrez Gene) | |
POLR2C | GeneProduct | 5432 (Entrez Gene) | |
POLR2D | GeneProduct | 5433 (Entrez Gene) | |
POLR2E | GeneProduct | 5434 (Entrez Gene) | |
POLR2G | GeneProduct | 5436 (Entrez Gene) | |
POLR2H | GeneProduct | 5437 (Entrez Gene) | |
POLR2I | GeneProduct | 5438 (Entrez Gene) | |
POLR2J1 | GeneProduct | 5439 (Entrez Gene) | |
POLR2J2 | GeneProduct | 246721 (Entrez Gene) | |
POLR2J3 | GeneProduct | 548644 (Entrez Gene) | |
POLR2K | GeneProduct | 5440 (Entrez Gene) | |
POLR2L | GeneProduct | 5441 (Entrez Gene) | |
POLR3A | GeneProduct | 11128 (Entrez Gene) | |
POLR3B | GeneProduct | 55703 (Entrez Gene) | |
POLR3C | GeneProduct | 10623 (Entrez Gene) | |
POLR3D | GeneProduct | 661 (Entrez Gene) | |
POLR3E | GeneProduct | 55718 (Entrez Gene) | |
POLR3F | GeneProduct | 10621 (Entrez Gene) | |
POLR3G | GeneProduct | 10622 (Entrez Gene) | |
POLR3GL | GeneProduct | 84265 (Entrez Gene) | |
POLR3H | GeneProduct | 171568 (Entrez Gene) | |
POLR3K | GeneProduct | 51728 (Entrez Gene) | |
PRIM1 | GeneProduct | 5557 (Entrez Gene) | |
PRIM2 | GeneProduct | 5558 (Entrez Gene) | |
PRPP | Metabolite | C00119 (KEGG Compound) | 5-Phospho-alpha-D-ribose 1-diphosphate |
Pentose phosphate pathway | Pathway | http://www.kegg.jp/dbget-bin/www_bget?mtu00030 | |
RNA | Metabolite | C00046 (KEGG Compound) | |
RRM1 | GeneProduct | 6240 (Entrez Gene) | Original kegg element: gene;60;mtu:Rv0233 mtu:Rv0570 mtu:Rv1981c mtu:Rv3048c mtu:Rv3051c |
RRM2 | GeneProduct | 6241 (Entrez Gene) | Original kegg element: gene;60;mtu:Rv0233 mtu:Rv0570 mtu:Rv1981c mtu:Rv3048c mtu:Rv3051c |
RRM2B | GeneProduct | 50484 (Entrez Gene) | Original kegg element: gene;60;mtu:Rv0233 mtu:Rv0570 mtu:Rv1981c mtu:Rv3048c mtu:Rv3051c |
TK1 | GeneProduct | 7083 (Entrez Gene) | |
TK2 | GeneProduct | 7084 (Entrez Gene) | |
TWISTNB | GeneProduct | 221830 (Entrez Gene) | |
TYMP | GeneProduct | 1890 (Entrez Gene) | |
TYMS | GeneProduct | 7298 (Entrez Gene) | Original kegg element: gene;6;mtu:Rv2754c |
Thymidine | Metabolite | HMDB0000273 (HMDB) | |
Thymine | Metabolite | HMDB0000262 (HMDB) | |
UCK1 | GeneProduct | 83549 (Entrez Gene) | |
UCK2 | GeneProduct | 7371 (Entrez Gene) | |
UCKL1 | GeneProduct | 54963 (Entrez Gene) | |
UDP | Metabolite | C00015 (KEGG Compound) | |
UMP | Metabolite | HMDB0000288 (HMDB) | |
UMPS | GeneProduct | 7372 (Entrez Gene) | Check literature for directionality of enzyme |
UPB1 | GeneProduct | 51733 (Entrez Gene) | |
UPP1 | GeneProduct | 7378 (Entrez Gene) | Check literature for directionality of enzyme |
UPP2 | GeneProduct | 151531 (Enzyme Nomenclature) | Check literature for directionality of enzyme |
UPRT | GeneProduct | 139596 (Entrez Gene) | |
UTP | Metabolite | C00075 (KEGG Compound) | |
UppppU | Metabolite | C06198 (KEGG Compound) | P1,P4-Bis(5'-uridyl) tetraphosphate |
Uracil | Metabolite | HMDB0000300 (HMDB) | |
Uridine | Metabolite | HMDB0000296 (HMDB) | |
Valine, leucine and isoleucine metabolism | Pathway | http://www.kegg.jp/dbget-bin/www_bget?mtu00410 | |
ZNRD1 | GeneProduct | 30834 (Entrez Gene) | |
beta-Alanine metabolism | Pathway | http://www.kegg.jp/dbget-bin/www_bget?mtu00410 | |
beta-Alanine | Metabolite | HMDB0000056 (HMDB) | |
dCDP | Metabolite | C00705 (KEGG Compound) | |
dCMP | Metabolite | C00239 (KEGG Compound) | |
dCTP | Metabolite | C00458 (KEGG Compound) | |
dTDP | Metabolite | C00363 (KEGG Compound) | Deoxythymidine 5'-diphosphate |
dTMP | Metabolite | C00364 (KEGG Compound) | Deoxythymidine 5'-phosphate |
dTTP | Metabolite | C00459 (KEGG Compound) | Deoxythymidine 5'-triphosphate |
dUDP | Metabolite | C01346 (KEGG Compound) | |
dUMP | Metabolite | C00365 (KEGG Compound) | |
dUTP | Metabolite | C00460 (KEGG Compound) |
Annotated Interactions
No annotated interactions