Nucleotides anabolism

Nulceotides are synthesized from simple building blocks (de novo synthesis) or by the recycling of preformed bases (salvage synthesis). Purines and pyrimidines are built de novo from amino acids, tetrahydrofolate derivatives, NH₄⁺, ribose-5-P and CO₂.

The purines and pyrimidines de novo metabolic pathways seems to be very similar in all live organisms. They share diverse important precursors, as PRPP for example. In each pathway an amino acid is an important precursor: glycine for the purines and aspartate for the pyrimidines.

Since the total amount of nucleotides stored in the cell is very small, the number of nucleotides available can limit the rate of nucleic acids synthesis. Thereby the nucleotides synthesis must keep going during the nucleic acids synthesis.

 Salvage pathways

Mono-P nucleotides synthesis from nitrogen bases

Phosphoribosyltransferases (EC 2.4.2.7, 2.4.2.8, 2.4.2.9, 2.4.2.10), widely distributed, catalyze this kind of reactions:

Base + PRPP ribonucleoside-5’-P + PPi

The termodynamic equilibrium of this reaction lies far on the side of products formation. This, plus the fast hydrolysis of the PPi (inorganic pyrophosphate) by the inorganic-pyrophosphatase, makes this step irreversible.

Nucleosides phosphorylation

As nucleotides, nucleosides do not accumulate whitin the cell, and their blood and tissues concentrations are very small. Instead of this, many vertebrates cells contains kinases capable of converting the purine nucleosides into nucleotides. One of these enzymes is adenosine kinase, that catalyzes the reaction bellow:

Adenosine + ATP AMP + ADP

Nucleosides tri-P formation from mono-P ones:

Most of the reactions shown produces nucleotides mono-P. In the cells, a series of kinases (phosphotransferases) converte these mononucleotides to its di and tri-P forms, metabolic actives. The conversion reaction are the same to all cells.

Nucleosides Monophosphate Kinases (NMP Kinases):

They catalyze this kind of reactions:

(d)NMP (Nucleoside Mono-P) + ATP (d)NDP + ADP

The cell systems efficiency to phosphorilate ADP into ATP drives it forward (products formation direction).

These enzymes are specific to the base (except C and U) but inespecific to the pentose. There are four different enzymes to the catalyzes of: (1)GMP and dGMP; (2)AMP and dAMP (wich produces ADP that is reapidly phosphorylated to ATP by the glycolytic enzymes or in the oxidative phosphorylation); (3)CMP, dCMP and UMP; (4)dTMP.

Nucleosides Diphosphate Kinases (NDP kinases):

The general reaction is: N₁TP + N₂DP N₁DP + N₂TP;

whereas N₁ (donor) and N₂ (receptor) are purines or pyrimidines nucleotides or deoxyribonucleotides.

Unlike the first one, this enzyme is not specific to the base nor the pentose, although the donor is frequently the ATP, because its concentrations within the cells are very high.

The NDP kinases activity is high. As result, the tri-P cell concentrations are usually higher than the di and mono-P nucleotides ones.