Pyrimidine metabolism (Homo sapiens)

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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

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95459view14:22, 15 December 2017DeSlChanged faulty ID for NME (3 more were present).
95458view14:20, 15 December 2017DeSlChanged faulty ID for NME.
95457view14:18, 15 December 2017DeSlchanged kegg ortholog to corresponding NCBI protein ID
94174view10:20, 25 August 2017DeSlConnected last interactions
94125view16:29, 22 August 2017DeSlAdded last changes for reaction arrows, connected RNA polymerase to PW.
94124view15:39, 22 August 2017DeSlAdded NT5E to several conversions, connected reverse reaction lines
94123view15:29, 22 August 2017DeSlConnected reverse reaction between dUTP and dUDP
94122view15:21, 22 August 2017DeSlConnected DNA-polymerase node
94121view15:06, 22 August 2017DeSlWorked on reverse reactions, added genes for conversion from dTTP to DNA
94120view14:57, 22 August 2017DeSlGrouped several proteins, connected lines, completed reverse reactions
94119view14:46, 22 August 2017DeSlAdded nodes to PW (on the right below)
94118view10:34, 22 August 2017DeSlFixed reverse reactions from orotate to orotidine 5'-phosphate
94117view10:10, 22 August 2017DeSlModified description
94116view10:09, 22 August 2017DeSlModified description
94115view10:07, 22 August 2017DeSlConnected lines, grouped enzymes, created PW nodes
94114view12:24, 21 August 2017DeSlModified description
94113view12:17, 21 August 2017DeSlModified description
94112view12:12, 21 August 2017DeSlOntology Term : 'pyrimidine metabolic pathway' added !
93049view12:00, 27 July 2017Annahoekstra1New pathway

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NameTypeDatabase referenceComment
(R)-3-aminoisobutyrateMetaboliteC01205 (KEGG Compound)
(R)-3-ureidoisobutyrateMetaboliteC21029 (KEGG Compound)
(R)-dihydrothymineMetaboliteC21028 (KEGG Compound)
2-deoxy-D-ribose-1PMetabolite439287 (PubChem-compound)
3-UreidopropionateMetaboliteC02642 (KEGG Compound)
5,6-DihydrouracilMetaboliteC00429 (KEGG Compound)
AK9GeneProductNP_001138600 (NCBI Protein) Check literature for directionality of enzyme
Alanine, aspartate and glutamate metabolismPathway
Arginine and proline metabolismPathway
CADGeneProduct790 (Entrez Gene) Original kegg element: gene;15;mtu:Rv1381
CANT1GeneProductNP_001153244 (NCBI Protein) Original kegg element: gene;111;mtu:Rv1021
CDAGeneProduct978 (Entrez Gene) Original kegg element: gene;48;mtu:Rv3315c
CDPMetaboliteC00112 (KEGG Compound)
CMPMetaboliteHMDB00095 (HMDB)
CMPK1GeneProduct51727 (Entrez Gene) Original kegg element: gene;4;mtu:Rv2883c
CMPK2GeneProduct129607 (Entrez Gene) Original kegg element: gene;4;mtu:Rv2883c
CTPMetaboliteC00063 (KEGG Compound)
CTPS1GeneProduct1503 (Entrez Gene) Original kegg element: gene;25;mtu:Rv0321
CTPS2GeneProduct56474 (Entrez Gene) Original kegg element: gene;25;mtu:Rv0321
CarbamoylphosphateMetaboliteHMDB01096 (HMDB)
CytidineMetaboliteHMDB00089 (HMDB)
DCKGeneProduct1633 (Entrez Gene)
DCTDGeneProduct1635 (Entrez Gene)
DCTPP1GeneProduct79077 (Entrez Gene)
DHODHGeneProduct1723 (Entrez Gene) Original kegg element: gene;17;mtu:Rv2139
DNAMetaboliteC00039 (KEGG Compound)
DPYDGeneProduct1806 (Entrez Gene)
DPYSGeneProduct1807 (Entrez Gene)
DPYSGeneProductNP_001376 (NCBI Protein)
DTYMKGeneProduct1841 (Entrez Gene) Original kegg element: gene;85;mtu:Rv3247c
DUTGeneProduct1854 (Entrez Gene) Original kegg element: gene;70;mtu:Rv2697c
DeoxycytidineMetaboliteC00881 (KEGG Compound)
DeoxyuridineMetaboliteHMDB00012 (HMDB)
DihydroorotateMetaboliteHMDB03349 (HMDB)
DiphosphateMetaboliteCHEBI:45212 (ChEBI)
ENPP1GeneProduct5167 (Entrez Gene) Original kegg element: gene;26;mtu:Rv1699
ENPP3GeneProduct5169 (Entrez Gene) Original kegg element: gene;26;mtu:Rv1699
ENTPD1GeneProduct953 (Entrez Gene)
ENTPD1GeneProductNP_001767 (NCBI Protein)
ENTPD3GeneProduct956 (Entrez Gene)
ENTPD3GeneProductNP_001239 (NCBI Protein)
ENTPD4GeneProductNP_004892 (NCBI Protein) Original kegg element: gene;111;mtu:Rv1021
ENTPD5GeneProductNP_001240 (NCBI Protein) Original kegg element: gene;111;mtu:Rv1021
ENTPD6GeneProductNP_001238 (NCBI Protein) Original kegg element: gene;111;mtu:Rv1021
ENTPD8GeneProductNP_001028285 (NCBI Protein)
L-GlutamineMetaboliteHMDB00641 (HMDB)
N-CarbamoylaspartateMetaboliteHMDB00828 (HMDB)
NME1-NME2GeneProduct654364 (Entrez Gene)
NME1GeneProduct4830 (Entrez Gene)
NMEGeneProduct2.7.4.6 (Enzyme Nomenclature)
NME2GeneProduct4831 (Entrez Gene)
NME3GeneProduct4832 (Entrez Gene)
NME4GeneProduct4833 (Entrez Gene)
NME6GeneProduct10201 (Entrez Gene)
NME7GeneProduct29922 (Entrez Gene)
NT5CGeneProduct30833 (Entrez Gene)
NT5EGeneProductNP_002517 (NCBI Protein)
NT5MGeneProduct56953 (Entrez Gene)
NUDT2GeneProductNP_001152 (NCBI Protein)
OrotateMetaboliteC00295 (KEGG Compound)
Orotidine 5'-phosphateMetaboliteC01103 (KEGG Compound)
PNPGeneProductNP_000261 (NCBI Protein)
PNPT1GeneProduct87178 (Entrez Gene) Original kegg element: gene;41;mtu:Rv2783c
PNPT1GeneProductNP_149100 (NCBI Protein)
POLA1GeneProduct5422 (Entrez Gene)
POLA2GeneProduct23649 (Entrez Gene)
POLD1GeneProduct5424 (Entrez Gene)
POLD2GeneProduct5425 (Entrez Gene)
POLD3GeneProduct10714 (Entrez Gene)
POLD4GeneProduct57804 (Entrez Gene)
POLE1GeneProduct5426 (Entrez Gene)
POLE2GeneProduct5427 (Entrez Gene)
POLE3GeneProduct54107 (Entrez Gene)
POLE4GeneProduct56655 (Entrez Gene)
POLR1AGeneProduct25885 (Entrez Gene)
POLR1BGeneProduct84172 (Entrez Gene)
POLR1CGeneProduct9533 (Entrez Gene)
POLR1DGeneProduct51082 (Entrez Gene)
POLR1EGeneProduct64425 (Entrez Gene)
POLR2AGeneProduct5430 (Entrez Gene)
POLR2BGeneProduct5431 (Entrez Gene)
POLR2CGeneProduct5432 (Entrez Gene)
POLR2DGeneProduct5433 (Entrez Gene)
POLR2EGeneProduct5434 (Entrez Gene)
POLR2GGeneProduct5436 (Entrez Gene)
POLR2HGeneProduct5437 (Entrez Gene)
POLR2IGeneProduct5438 (Entrez Gene)
POLR2J1GeneProduct5439 (Entrez Gene)
POLR2J2GeneProduct246721 (Entrez Gene)
POLR2J3GeneProduct548644 (Entrez Gene)
POLR2KGeneProduct5440 (Entrez Gene)
POLR2LGeneProduct5441 (Entrez Gene)
POLR3AGeneProduct11128 (Entrez Gene)
POLR3BGeneProduct55703 (Entrez Gene)
POLR3CGeneProduct10623 (Entrez Gene)
POLR3DGeneProduct661 (Entrez Gene)
POLR3EGeneProduct55718 (Entrez Gene)
POLR3FGeneProduct10621 (Entrez Gene)
POLR3GGeneProduct10622 (Entrez Gene)
POLR3GLGeneProduct84265 (Entrez Gene)
POLR3HGeneProduct171568 (Entrez Gene)
POLR3KGeneProduct51728 (Entrez Gene)
PRIM1GeneProduct5557 (Entrez Gene)
PRIM2GeneProduct5558 (Entrez Gene)
PRPPMetaboliteC00119 (KEGG Compound) 5-Phospho-alpha-D-ribose 1-diphosphate
Pentose phosphate pathwayPathway
RNAMetaboliteC00046 (KEGG Compound)
RRM1GeneProduct6240 (Entrez Gene) Original kegg element: gene;60;mtu:Rv0233 mtu:Rv0570 mtu:Rv1981c mtu:Rv3048c mtu:Rv3051c
RRM2GeneProduct6241 (Entrez Gene) Original kegg element: gene;60;mtu:Rv0233 mtu:Rv0570 mtu:Rv1981c mtu:Rv3048c mtu:Rv3051c
RRM2BGeneProduct50484 (Entrez Gene) Original kegg element: gene;60;mtu:Rv0233 mtu:Rv0570 mtu:Rv1981c mtu:Rv3048c mtu:Rv3051c
TK1GeneProduct7083 (Entrez Gene)
TK2GeneProduct7084 (Entrez Gene)
TWISTNBGeneProduct221830 (Entrez Gene)
TYMPGeneProduct1890 (Entrez Gene)
TYMSGeneProduct7298 (Entrez Gene) Original kegg element: gene;6;mtu:Rv2754c
ThymidineMetaboliteHMDB00273 (HMDB)
ThymineMetaboliteHMDB00262 (HMDB)
UCK1GeneProduct83549 (Entrez Gene)
UCK2GeneProduct7371 (Entrez Gene)
UCKL1GeneProduct54963 (Entrez Gene)
UDPMetaboliteC00015 (KEGG Compound)
UMPMetaboliteHMDB00288 (HMDB)
UMPSGeneProduct7372 (Entrez Gene) Check literature for directionality of enzyme
UPB1GeneProduct51733 (Entrez Gene)
UPP1GeneProduct7378 (Entrez Gene) Check literature for directionality of enzyme
UPP2GeneProduct151531 (Enzyme Nomenclature) Check literature for directionality of enzyme
UPRTGeneProduct139596 (Entrez Gene)
UTPMetaboliteC00075 (KEGG Compound)
UppppUMetaboliteC06198 (KEGG Compound) P1,P4-Bis(5'-uridyl) tetraphosphate
UracilMetaboliteHMDB00300 (HMDB)
UridineMetaboliteHMDB00296 (HMDB)
Valine, leucine and isoleucine metabolismPathway
ZNRD1GeneProduct30834 (Entrez Gene)
beta-Alanine metabolismPathway
beta-AlanineMetaboliteHMDB00056 (HMDB)
dCDPMetaboliteC00705 (KEGG Compound)
dCMPMetaboliteC00239 (KEGG Compound)
dCTPMetaboliteC00458 (KEGG Compound)
dTDPMetaboliteC00363 (KEGG Compound) Deoxythymidine 5'-diphosphate
dTMPMetaboliteC00364 (KEGG Compound) Deoxythymidine 5'-phosphate
dTTPMetaboliteC00459 (KEGG Compound) Deoxythymidine 5'-triphosphate
dUDPMetaboliteC01346 (KEGG Compound)
dUMPMetaboliteC00365 (KEGG Compound)
dUTPMetaboliteC00460 (KEGG Compound)

Annotated Interactions

No annotated interactions

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