Pyrimidine metabolism

Pyrimidine biosynthesis occurs both in the body and through organic synthesis.

De novo biosynthesis of pyrimidine

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

The synthesis of UMP.

The color scheme is as follows: enzymes, coenzymes, substrate names, inorganic molecules

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 (CAD).

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.

External links

• Overview at Queen Mary, University of London