The synthesis of pyrimidine nucleotides u, c, t

Uridin monophosphate is synthesized from CO₂, Gln, Asp. It is a precursor of cytidylic and thymidylic pyrimidine nucleotides.

The first reaction is the formation of carbamoyl phosphate by the action of carbamoyl phosphate synthetase II (glutamine dependent; is found in cytosol).

CO₂ + Glutamine + 2 ATP + H₂O  H₂NCO OPO₃H₂ +

+ 2 ADP + H₃PO₄.

Then carbamoyl phosphate reacts with aspartate. Uridylic acid is formed as a result of series of reactions.

CP + Asp  …

 orotydylic  acid

Orotic aciduria is urinary excretion of large amounts of orotic acid. Hereditary orotic aciduria is known at which up to 1.5 g of orotic acid per day is excreted, 1000 times more than in norm. The disease is associated with a deficiency of the enzyme catalyzing the synthesis and decarboxylation of orotidilic acid. Hereditary orotic aciduria leads to an irreversible retarded growth and mental retardation. Usually patients die in the first years of life. Orotic acid is not toxic. Disorders are the result of "pyrimidine starvation". Therefore, uridine is used for the treatment of this disease.

Uridine-5'-phosphate can be further converted to other pyrimidine nucleotides by the reactions:

- reduction - hydrogen donor is protein thioredoxin, which contains SH-groups;

- amination - Gln is a donor of amino group;

- methylation - methylene H₄-folate is a donor of methyl group.

Pyrimidine nucleoside triphosphates are synthesized in the interaction with ATP.

UMP + ATP  UDP + ADP

UDP + ATP  UTP + ADP

Biosynthesis of purine bases A, T

The formation of the purine ring immediately occurs on the ribose-5-phosphate. As a result of sequential reactions inosine-5'-phosphate (inosinic acid) is formed.

Glycine, aspartate, glutamine, carbon dioxideand derivatives of tetrahydrofolic acid are donors of carbon and nitrogen atoms for the purine ring.

Inosine-5'-phosphate is oxidized to xantozin-5'-phosphate. As a result of inosine-5'-phosphate amination adenosine-5'-phosphate is formed, and the xantosine-5'-phosphate amination gives guanosine-5'-phosphate.

I nosine-5'-phosphate Xantosine-5'-phosphate

+ Asp - fumarate + Gln - Glu

+ GTP - GDP, -P_i + ATP - AMP, -PP_i

Adenosine-5'-phosphate Guanosine-5'-phosphate

Purine nucleosides, as well as pyrimidine nucleosides, are converted to nucleoside triphosphates in the reaction with ATP. Purine nucleotide synthesis is controlled by a feedback mechanism.

The synthesis of deoxyribonucleotides

Deoxyribonucleotides are formed from ribonucleotides by a reduction of ribose residue which is catalyzed by the enzyme ribonucleotide reductase.

Tioredoxin reductase catalyzes the hydrogenation of oxidized thioredoxin.

Deoxyribonucleoside diphosphates are converted to deoxyribonucleoside triphosphates by the kinases action.

dGDF + ATP dGTP + ADP