How much ATP is required for de novo synthesis of purines

Purines are synthesized in one of two ways: in a de novo pathway from amino acid and other building blocks or via a salvage pathway from nucleic acid turnover.

PRECURSOR of purine synthesis de novo ..

Nucleotide Metabolism De novo synthesis of purines IMP is the precursor of both from BCH 462 at ASU

-->Features of de novo pathway of purine synthesis: 1) ..

An S, Kumar R, Sheets ED and Benkovic SJ (2008) Reversible compartmentalization of de novo purine biosynthetic complexes in living cells. Science 320: 103–106.

What is the precursor of AMP and GMP in de novo purine synthesis

Overview of the pathways for the biosynthesis of purine and pyrimidine nucleotides (THF, tetrahydrofolate). Ribonucleoside triphosphates are blue; deoxyribonucleoside triphosphates are green. To emphasise that it is not a building block for deoxyribonucleic acid (DNA) synthesis dUTP is red. Both pathways start from a common set of precursor amino acids and other metabolites. Each arrow represents an enzymatic reaction.

elevated expression of de novo purine synthesis is a specific ..

Nucleosides are composed of a heterocyclic ring (defined as the base) that is attached to a ribose. Addition of a phosphate to a nucleoside, at carbon 5 of the ribose, produces a nucleotide. Nucleotides function as ubiquitous building blocks for the synthesis of all nucleic acids, and also function in enzymatic reactions as cofactors and as a source of energy. These central metabolic roles require their continued biosynthesis from readily available precursors, and this process is defined as nucleotide synthesis. The synthesis of purines starts with ribose‐phosphate, to which are attached the individual atoms of the heterocyclic base in a stepwise fashion. Pyrimidine synthesis starts with the stepwise formation of the base, to which is then added the ribose‐phosphate. Bases and nucleosides may also be recycled in salvage pathways.

Regulation of de novo purine synthesis in human ..

Three major feedback mechanisms cooperate in regulating the overall rate ofde novo purine nucleotide synthesis and the relative rates of formation of thetwo end products, adenylate and guanylate (Fig. 16–3). The first mechanism isexerted on the first reaction that is unique to purine synthesis—transfer of anamino group to PRPP to form 5-phosphoribosylamine. This reaction is catalyzed bythe allosteric enzyme glutamine-PRPP amidotransferase, which is inhibited by theend products IMP, AMP, and GMP. AMP and GMP act synergistically in thisconcerted inhibition. Thus, whenever either AMP or GMP accumulates to excess,the first step in its biosynthesis from PRPP is partially inhibited.
In the second control mechanism, exerted at a later stage, an excess of GMP inthe cell inhibits formation of xanthylate from inosinate by IMP dehydrogenase,without affecting the formation of AMP (Fig. 16–3). Conversely, an accumulationof adenylate inhibits formation of adenylosuccinate by adenylosuccinatesynthetase, without affecting the biosynthesis of GMP. In the third mechanism,GTP is required in the conversion of IMP to AMP (Fig. 16–2, step 1), whereas ATPis required for conversion of IMP to GMP (step 4), a reciprocal arrangement thattends to balance the synthesis of the two ribonucleotides.
The final control mechanism is the inhibition of PRPP synthesis by theallosteric regulation of ribose phosphate pyrophosphokinase. This enzyme isinhibited by ADP and GDP, in addition to metabolites from other pathways ofwhich PRPP is a starting point.

Pyrimidine and purine metabolism ..

In previous studies from this laboratory, human bone marrow hypoxanthine concentrations were found to average 7.1 microM, three times higher than plasma hypoxanthine concentrations measured simultaneously. To assess the significance of this finding, the relationship between hypoxanthine concentration and the rate of purine nucleotide synthesis by the de novo pathway was studied in normal human bone marrow mononuclear cells and in the human promyelocytic cell line, HL-60, in vitro. Utilizing a [14C]formate incorporation technique, rates of total cellular de novo purine synthesis as well as rates of de novo adenine, de novo guanine, and thymine synthesis and incorporation into RNA and DNA were measured as a function of hypoxanthine concentration. In normal human marrow cells, the rate of total de novo purine synthesis declined by 81%, while the rate of de novo adenine and de novo guanine synthesis and incorporation into macromolecules declined by 89 and 75%, respectively, when media hypoxanthine was increased from 0 to 10 microM. Similar results were seen in the HL-60 cell line. In contrast, rates of thymine synthesis and incorporation into DNA as well as overall rates of RNA and DNA synthesis did not change with varying media hypoxanthine concentrations. In addition, hypoxanthine salvage and incorporation into RNA and DNA was shown to progressively increase with increasing media hypoxanthine concentrations. These results indicate that physiologic concentrations of hypoxanthine are sufficient to regulate the rate of de novo purine synthesis in human bone marrow in vivo.