Pyrimidine metabolism

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Pyrimidine biosynthesis occurs both in the body and through organic synthesis.^[1]

De novo biosynthesis of pyrimidine

Steps	Enzymes	Products
1	carbamoyl phosphate synthetase II[2]	carbamoyl phosphate	This is the regulated step in the pyrimidine biosynthesis in animals.
2	aspartic transcarbamoylase ( aspartate carbamoyl transferase)[2]	carbamoyl aspartic acid	The phosphate group is replaced with Aspartate. This is the regulated step in the pyrimidine biosynthesis in bacteria.
3	dihydroorotase[2]	dihydroorotate	Ring formation and Dehydration.
4	dihydroorotate dehydrogenase[3] (the only mitochondrial enzyme)	orotate	Dihydroorotate then enters the mitochondria where it is oxidized through removal of hydrogens. This is the only mitochondrial step in nucleotide rings biosynthesis.
5	orotate phosphoribosyltransferase[4]	OMP	PRPP donates a Ribose group.
6	OMP decarboxylase[4]	UMP	Decarboxylation
	uridine-cytidine kinase 2[5]	UDP	Phosphorylation. ATP is used.
	nucleoside diphosphate kinase	UTP	Phosphorylation. ATP is used.
	CTP synthase	CTP	Glutamine and ATP are used.

De Novo biosynthesis of a

, a similar protein exists but lacks the dihydroorotase function: another protein catalyzes the second step.

In other organisms (

Pyrimidine catabolism

.

β-aminoisobutyrate acts as a rough indicator for rate of DNA turnover.^[8]

Regulations of pyrimidine nucleotide biosynthesis

Through negative feedback inhibition, the end-products UTP and UDP prevent the enzyme CAD from catalyzing the reaction in animals. Conversely, PRPP and ATP act as positive effectors that enhance the enzyme's activity.^[9]

Pharmacotherapy

Modulating the pyrimidine metabolism pharmacologically has therapeutical uses, and could implement in cancer treatment.^[10]

Pyrimidine synthesis inhibitors are used in active moderate to severe rheumatoid arthritis and psoriatic arthritis, as well as in multiple sclerosis. Examples include Leflunomide and Teriflunomide (the active metabolite of leflunomide).

Prebiotic synthesis of pyrimidine nucleotides

In order to understand how life arose, knowledge is required of the chemical pathways that permit formation of the key building blocks of life under plausible prebiotic conditions. The RNA world hypothesis holds that in the primordial soup there existed free-floating pyrimidine and purine ribonucleotides, the fundamental molecules that combine in series to form RNA. Complex molecules such as RNA must have emerged from relatively small molecules whose reactivity was governed by physico-chemical processes. RNA is composed of pyrimidine and purine nucleotides, both of which are necessary for reliable information transfer, and thus natural selection and Darwinian evolution. Becker et al. showed how pyrimidine nucleosides can be synthesized from small molecules and ribose, driven solely by wet-dry cycles.^[11]

References

External links

• Overview at
  Queen Mary, University of London