Pyrimidine metabolism

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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 External links

[edit] De novo biosynthesis of pyrimidine

Unlike purines, pyrimidines are assembled before being attached to 5-phosphoribosyl-1-pyrophosphate (PRPP).

Enzyme	Product	Description
carbamoyl phosphate synthetase II	carbamoyl phosphate	This is the regulated step in the pyrimidine biosynthesis.
aspartic transcarbamolyase (aspartate carbamoyl transferase	carbamoyl aspartic acid	-
dihhydroorotase	dihydroorotate	Dehydration
dihydroorotate dehydrogenase (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	OMP	PRPP is used.
OMP decarboxylase	UMP	Decarboxylation
nucleoside monophosphate kinase	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.

[edit] 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. 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.^{[citation needed]}

[edit] Pharmacotherapy

Modulating the pyrimidine metabolism pharmacologically has therapeutical uses.

Pyrimidine synthesis inhibitors are used in active moderate to severe rheumatoid arthritis and psoriasis arthritis. Examples include Leflunomide.

[edit] External links

• Overview at Queen Mary, University of London

v • d • e Metabolism map Glucuronate metabolism Pentose interconversion Inositol metabolism Cellulose and sucrose metabolism Starch and glycogen metabolism Other sugar metabolism Pentose phosphate pathway Glycolysis and Gluconeogenesis Amino sugars metabolism Small amino acid synthesis Branched amino acid synthesis Purine biosynthesis Histidine metabolism Aromatic amino acid synthesis Pyruvate decarboxylation Anaerobic respiration Fatty acid metabolism Urea cycle Aspartate amino acid group synthesis Porphyrins and corrinoids metabolism Citric acid cycle Glutamate amino acid group synthesis Pyrimidine biosynthesis  v • d • e  All pathway labels on this image are links, simply click to access the article. A high resolution labeled version of this image is available here.

v • d • e Protein metabolism: protein metabolism Protein synthesis - Amino acid synthesis - Catabolism Nucleotide metabolism: Purine metabolism - Nucleotide salvage - Pyrimidine metabolism

v • d • e Metabolism: amino acid metabolism - nucleotide enzymes Purine metabolism Anabolism R5P->IMP: Ribose-phosphate diphosphokinase - Amidophosphoribosyltransferase - Phosphoribosylglycinamide formyltransferase - AIR synthetase (FGAM cyclase) - Phosphoribosylaminoimidazole carboxylase - Phosphoribosylaminoimidazolesuccinocarboxamide synthase - IMP synthase IMP->AMP: Adenylosuccinate synthase - Adenylosuccinate lyase - reverse (AMP deaminase) IMP->GMP: IMP dehydrogenase - GMP synthase - reverse (GMP reductase) Nucleotide salvage Hypoxanthine-guanine phosphoribosyltransferase - Adenine phosphoribosyltransferase Catabolism Adenosine deaminase - Purine nucleoside phosphorylase - Guanine deaminase - Xanthine oxidase - Urate oxidase Pyrimidine metabolism Anabolism CAD (Carbamoyl phosphate synthase II, Aspartate carbamoyltransferase, Dihydroorotase) Dihydroorotate dehydrogenase - Orotidine 5'-phosphate decarboxylase/Uridine monophosphate synthetase CTP synthase Catabolism Dihydropyrimidine dehydrogenase - Dihydropyrimidinase/DPYS - Beta-ureidopropionase/UPB1 Deoxyribonucleotides Ribonucleotide reductase - Nucleoside-diphosphate kinase - DCMP deaminase - Thymidylate synthase - Dihydrofolate reductase see also disorders, intermediates