Pyrimidine metabolism and related diseases (Homo sapiens)
From WikiPathways
Description
Overview of pyrimidine metabolism and related diseases. Pyrimidine metabolism is important for the synthesis of thymine, cytosine and uracil, some of the building blocks for DNA and RNA and they also have functions in signal transduction and energy transport. The pathway can be split up in 3 parts, one is the de novo synthesis of pyrimidines, starting with glutamine and ending at UMP. From here the UMP can either be used in the nucleic acid synthesis (up) or broken down to Beta-alanine or (S)-beta-aminoisobutyrate.
Disorders in the metabolism of pyrimidine are mostly caused by enzyme defects (highlighted in pink, one disease is depicted in orange, since there appears to be no clinical difference between type 2 and 1 of orotic aciduria, therefore researchers believe that type 2 does not exist officially). The clinical presentation of pyrimidine disorders is very diverse, because of the diversity in biological function. The severity of the disorder is determined by the severity of the defect and the function of the normal enzyme.
Metabolic markers are highlighted in dark purple. Complexes mentioned in pathway are pictured in bottom left corner. The link to the Urea cycle is depicted for clarity.
This pathway was inspired by Chapter 41 of the book of Blau (ISBN 3642403360 (978-3642403361)).Quality Tags
Ontology Terms
Bibliography
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- Natalia Y. Kedishvili, Gary W. Goodwin, Kirill M. Popov, Robert A. Harris; ''Mammalian Methylmalonate-Semialdehyde Dehydrogenase''; Methods Enzymol., 2007 PubMed Europe PMC Scholia
- Dmitrii A Tanianskii, Natalia Jarzebska, Andreas L Birkenfeld, John F O'Sullivan, Roman N Rodionov; ''Beta-Aminoisobutyric Acid as a Novel Regulator of Carbohydrate and Lipid Metabolism''; Nutrients, 2019 PubMed Europe PMC Scholia
- van Kuilenburg AB; ''Dihydropyrimidine dehydrogenase and the efficacy and toxicity of 5-fluorouracil''; Eur J Cancer, 2004 PubMed Europe PMC Scholia
- J J Higgins, C R Kaneski, I Bernardini, R O Brady, N W Barton; ''Pyridoxine-responsive hyper-beta-alaninemia associated with Cohen's syndrome''; Neurology, 1994 PubMed Europe PMC Scholia
- Blau, N., Duran, M., Gibson, K.M., Donisi-Vici, C.; ''Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, Chapter 41''; ISBN 978-3-642-40337-8, 2014
- Qiu W, Zhou B, Darwish D, Shao J, Yen Y; ''Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits.''; , 2006 PubMed Europe PMC Scholia
- Shanti Balasubramaniam, John A. Duley, John Christodoulou; ''Inborn errors of pyrimidine metabolism: clinical update and therapy''; Journal of Inherited Metabolic Disease, 2014 PubMed Europe PMC Scholia
- Assmann B, Gohlich G, Baethmann M, Wevers RA, et al.; ''Clinical findings and a therapeutic trial in the first patient with beta-ureidopropionase deficiency''; Neuropediatrics, 2006 PubMed Europe PMC Scholia
- Kaymak I, Maier CR, Schmitz W, Campbell AD, Dankworth B, Ade CP, Walz S, Paauwe M, Kalogirou C, Marouf H, Rosenfeldt MT, Gay DM, McGregor GH, Sansom OJ, Schulze A; ''Mevalonate Pathway Provides Ubiquinone to Maintain Pyrimidine Synthesis and Survival in p53-Deficient Cancer Cells Exposed to Metabolic Stress.''; Cancer Res, 2020 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
(S)-Beta-aminoisobutyrate | Metabolite | CHEBI:57731 (ChEBI) ![]() |
|
+ PRPP | Metabolite | CHEBI:17111 (ChEBI) ![]() | |
2-Deoxyuridine | Metabolite | CHEBI:16450 (ChEBI) ![]() | |
ABAT | Protein | P80404 (Uniprot-TrEMBL) ![]() | |
ACT | Protein | 2.1.3.2 (Enzyme Nomenclature) ![]() | |
ACT | Protein | 2.1.3.2 (KEGG Genes) ![]() | |
AGXT2 | Protein | Q9BYV1 (Uniprot-TrEMBL) ![]() | |
AKT | Protein | AKA beta-alanine-alpha-ketoglutarate transaminase; or beta-alanyl-alpha-ketoglutarate transaminase (AKT) [PMID:7936305]. No annotations found in UniProt related to this name | |
Acetyl-CoA | Metabolite | CHEBI:15351 (ChEBI) ![]() | |
Aspartate | Metabolite | CHEBI:29991 (ChEBI) ![]() | (1-) charge needed for conversion to take place |
Beta-alanine | Metabolite | CHEBI:57966 (ChEBI) ![]() | Zwitterion needed for conversion to take place |
CAD-complex | GeneProduct | P27708 (Uniprot-TrEMBL) ![]() | |
CDP | Metabolite | CHEBI:58069 (ChEBI) ![]() | (3-) charge needed for conversion to take place |
CMP | Metabolite | CHEBI:60377 (ChEBI) ![]() | (2-) charge needed for conversion to take place |
CPS1 | Protein | P31327 (Uniprot-TrEMBL) ![]() | |
CPS2 | Protein | 6.3.5.5 (Enzyme Nomenclature) ![]() | |
CTP | Metabolite | CHEBI:37563 (ChEBI) ![]() | (4-) charge needed for conversion to take place |
Carbamoyl-phosphate | Metabolite | CHEBI:58228 (ChEBI) ![]() | (2-) charge needed for conversion to take place |
Carbamoylaspartate | Metabolite | CHEBI:32814 (ChEBI) ![]() |
|
Citrulline | Metabolite | CHEBI:57743 (ChEBI) ![]() | Zwitterion needed for conversion to take place |
CoQ10 - H2 (reduced) | Metabolite | CHEBI:64183 (ChEBI) ![]() | |
CoQ10 | Metabolite | CHEBI:46245 (ChEBI) ![]() | |
Cytidine | Metabolite | CHEBI:17562 (ChEBI) ![]() | |
D-methylmalonate semialdehyde | Metabolite | CHEBI:141212 (ChEBI) ![]() |
|
DHO | Protein | 3.5.2.3 (Enzyme Nomenclature) ![]() | |
DHODH | Protein | Q02127 (Uniprot-TrEMBL) ![]() | |
DHP | Protein | Q14117 (Uniprot-TrEMBL) ![]() | AKA DPYS |
DPD | Protein | Q12882 (Uniprot-TrEMBL) ![]() | AKA DPYD |
Dihydroorotate | Metabolite | CHEBI:30864 (ChEBI) ![]() | |
Dihydrothymine | Metabolite | CHEBI:27468 (ChEBI) ![]() | |
Dihydrouracil | Metabolite | CHEBI:15901 (ChEBI) ![]() | |
GLS2 | Protein | Q9UI32 (Uniprot-TrEMBL) ![]() | |
Glutamate | Metabolite | CHEBI:29985 (ChEBI) ![]() | (1-) charge needed for conversion to take place |
Glutamine | Metabolite | CHEBI:58359 (ChEBI) ![]() | Zwitterion needed for conversion to take place |
HCO3- | Metabolite | CHEBI:17544 (ChEBI) ![]() | |
L-BAIBA | Metabolite | CHEBI:58655 (ChEBI) ![]() | L form of β-aminoisobutyric acid (BAIBA) |
L-Valine | Metabolite | CHEBI:57762 (ChEBI) ![]() | |
L-methylmalonate semialdehyde | Metabolite | CHEBI:62413 (ChEBI) ![]() |
|
MMSDH | Protein | Q02252 (Uniprot-TrEMBL) ![]() | |
Malonate semialdehyde | Metabolite | CHEBI:57700 (ChEBI) ![]() |
|
N-Carbamoyl-beta-alanine | Metabolite | CHEBI:11892 (ChEBI) ![]() | aka 3-(carbamoylamino)propanoate |
N-Carbamyl-beta-aminoisobutyric acid | Metabolite | CHEBI:74414 (ChEBI) ![]() |
|
NH4+ | Metabolite | CHEBI:28938 (ChEBI) ![]() | |
OMP | Metabolite | CHEBI:57538 (ChEBI) ![]() |
|
OMPDC | Protein | 4.1.1.23 (Enzyme Nomenclature) ![]() | |
OPRT | Protein | 2.4.2.10 (Enzyme Nomenclature) ![]() | |
OTC | Protein | P00480 (Uniprot-TrEMBL) ![]() | |
Ornithine | Metabolite | CHEBI:46911 (ChEBI) ![]() | (1) charge needed for conversion to take place |
Orotate | Metabolite | CHEBI:30839 (ChEBI) ![]() | |
Orotidine | Metabolite | CHEBI:25722 (ChEBI) ![]() | |
PRPP | Metabolite | CHEBI:17111 (ChEBI) ![]() | |
Propionyl-CoA | Metabolite | CHEBI:57392 (ChEBI) ![]() | |
RR | Protein | 1.17.4.1 (Enzyme Nomenclature) ![]() | |
RRM1 | Protein | P23921 (Uniprot-TrEMBL) ![]() | |
RRM2B | Protein | Q7LG56 (Uniprot-TrEMBL) ![]() | |
RRM2 | Protein | P31350 (Uniprot-TrEMBL) ![]() | |
Riboflavin and CoQ disorders | Pathway | WP5037 (WikiPathways) ![]() | |
TK2 | Protein | O00142 (Uniprot-TrEMBL) ![]() | |
TP | Protein | P19971 (Uniprot-TrEMBL) ![]() | |
TS | Protein | P04818 (Uniprot-TrEMBL) ![]() | |
Thymidine | Metabolite | CHEBI:17748 (ChEBI) ![]() | |
Thymine | Metabolite | CHEBI:17821 (ChEBI) ![]() | |
Transamination and oxidative reactions | Pathway | WP4686 (WikiPathways) ![]() | |
UDP | Metabolite | CHEBI:58223 (ChEBI) ![]() | (3-) charge needed for conversion to take place |
UMP | Metabolite | CHEBI:57865 (ChEBI) ![]() | (2-) charge needed for conversion to take place |
UMPH1 | Protein | Q9H0P0 (Uniprot-TrEMBL) ![]() |
|
UMPH2 | Protein | Q8TCD5 (Uniprot-TrEMBL) ![]() |
|
UMPH | Protein | 3.1.3.5 (Enzyme Nomenclature) ![]() |
|
UMPS-complex | GeneProduct | P11172 (Uniprot-TrEMBL) ![]() | |
UP | Protein | Q9UBR1 (Uniprot-TrEMBL) ![]() | aka UPB1 |
UTP | Metabolite | CHEBI:46398 (ChEBI) ![]() | (4-) charge needed for conversion to take place |
Uracil | Metabolite | CHEBI:17568 (ChEBI) ![]() | |
Urea cycle | Pathway | WP4571 (WikiPathways) ![]() | |
Uridine | Metabolite | CHEBI:16704 (ChEBI) ![]() | |
beta-alanine-pyruvate transaminase | Protein | 2.6.1.18 (Enzyme Nomenclature) ![]() | |
dTMP | Metabolite | CHEBI:63528 (ChEBI) ![]() | (2-) charge needed for conversion to take place |
dUDP | Metabolite | CHEBI:60471 (ChEBI) ![]() | (3-) charge needed for conversion to take place |
dUMP | Metabolite | CHEBI:246422 (ChEBI) ![]() | (2-) charge needed for conversion to take place |
methylmalonate semialdehyde dehydrogenase | Protein |
Annotated Interactions
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Source | Target | Type | Database reference | Comment |
---|---|---|---|---|
(S)-Beta-aminoisobutyrate | D-methylmalonate semialdehyde | mim-conversion | 18394 (Rhea) ![]() | |
2-Deoxyuridine | Uracil | mim-conversion | 22825 (Rhea) ![]() | |
Aspartate | mim-conversion | 20014 (Rhea) ![]() | ||
CDP | CMP | mim-conversion | 11602 (Rhea) ![]() | |
CMP | Cytidine | mim-conversion | 24676 (Rhea) ![]() | |
CTP | CDP | mim-conversion | 25239 (Rhea) ![]() | |
Carbamoyl-phosphate | Carbamoylaspartate | mim-conversion | 20014 (Rhea) ![]() | |
Carbamoyl-phosphate | Citrulline | mim-conversion | 19514 (Rhea) ![]() | |
Carbamoylaspartate | Dihydroorotate | mim-conversion | 24298 (Rhea) ![]() | |
Cytidine | Uridine | mim-conversion | 16070 (Rhea) ![]() | |
D-methylmalonate semialdehyde | Propionyl-CoA | mim-conversion | 20805 (Rhea) ![]() | |
Dihydroorotate | Orotate | mim-conversion | 13514 (Rhea) ![]() | |
Dihydroorotate | Orotate | mim-conversion | 28692 (Rhea) ![]() | |
Dihydrothymine | N-Carbamyl-beta-aminoisobutyric acid | mim-conversion | 37336 (Rhea) ![]() | |
Dihydrouracil | N-Carbamoyl-beta-alanine | mim-conversion | 16122 (Rhea) ![]() | |
Glutamine | Carbamoyl-phosphate | mim-conversion | 18634 (Rhea) ![]() | |
Glutamine | Glutamate | mim-conversion | 15890 (Rhea) ![]() | |
HCO3- | mim-conversion | 18030 (Rhea) ![]() | ||
HCO3- | mim-conversion | 18634 (Rhea) ![]() | ||
N-Carbamoyl-beta-alanine | Beta-alanine | mim-conversion | 11185 (Rhea) ![]() | |
N-Carbamyl-beta-aminoisobutyric acid | (S)-Beta-aminoisobutyrate | mim-conversion | 37340 (Rhea) ![]() | |
NH4+ | Carbamoyl-phosphate | mim-conversion | 18030 (Rhea) ![]() | |
NH4+ | mim-conversion | 15890 (Rhea) ![]() | ||
OMP | UMP | mim-conversion | 11597 (Rhea) ![]() | |
Ornithine | mim-conversion | 19514 (Rhea) ![]() | ||
Orotate | OMP | mim-conversion | 10382 (Rhea) ![]() | |
Thymidine | Thymine | mim-conversion | 16038 (Rhea) ![]() | |
Thymidine | dTMP | mim-conversion | 19130 (Rhea) ![]() | |
Thymine | Dihydrothymine | mim-conversion | 28793 (Rhea) ![]() | |
UDP | UTP | mim-conversion | 25099 (Rhea) ![]() | |
UDP | dUDP | mim-conversion | 28028 (Rhea) ![]() | |
UMP | UDP | mim-conversion | 24401 (Rhea) ![]() | |
UMP | Uridine | mim-conversion | 29360 (Rhea) ![]() | |
UTP | CTP | mim-conversion | 30337 (Rhea) ![]() | |
Uracil | Dihydrouracil | mim-conversion | 20191 (Rhea) ![]() | |
Uridine | Uracil | mim-conversion | 24389 (Rhea) ![]() | |
dTMP | Thymidine | mim-conversion | 19131 (Rhea) ![]() | |
dUMP | 2-Deoxyuridine | mim-conversion | 28208 (Rhea) ![]() | |
dUMP | dTMP | mim-conversion | 12105 (Rhea) ![]() | |
dUMP | dUDP | mim-conversion | 30656 (Rhea) ![]() |