There is evidence that an interchange of purines among tissues may occur (1, 2) and that, for example, bone marrow obtains its purines from the liver (3). For this reason relative rates of purine synthesis de novo in organs, as indicated by incorporation of a radioactive precursor, may be ambiguous if measured at relatively long times after administration of the precursor. Therefore the synthes...

Nucleic acid biosynthesis of Angiostrongylus costaricensis was examined with various inhibitors; aminopterin (inhibitor of purine and pyrimidine de novo biosynthetic pathways), 8-azaguanine (specific inhibitor of purine salvage pathway) and PALA (specific inhibitor of pyrimidine de novo biosynthetic pathway) were applied in in vitro culture developing from the third stage larvae to young adult ...

Methylthioadenosine phosphorylase (MTAP), an enzyme involved in purine and methionine metabolism, is present in all normal tissues but is frequently deficient in a variety of cancers. It has been suggested that this metabolic difference between normal and cancer cells may be exploited to selectively treat MTAP-negative cancers by inhibiting de novo purine synthesis and by depleting L-methionine...

Armitt & Woods (1970) and Lomax & Woods (1973) reported the isolation of a series of mutants of Saccharomyces cerevisiae that did not require purines for growth, but excreted substantial amounts of purines into the growth medium. Genetic studies have assigned these yeast strains to six unlinked genes (purl, pur2, pur3, pur4, pur.5, pzv6), of which one, pur6, had both recessive and dominant (PUR...

The finding that the purine portions of both adenosine triphosphate and guanosine triphosphate of the mature rabbit erythrocyte are not metabolically stable constituents of that cell, as is the heme of hemoglobin, suggested the possibility of a metabolic renewal of the nucleotides during the life of the cell (1, 2). The absence of any detectable utilization of sodium formate-Cl4 or of glycine-2...

Methylthioadenosine phosphorylase, (MTAP) is a key enzyme in the adenine and methionine salvage pathways. MTAP is encoded on human chromosome 9p21 in close proximity to the p16INK4a and p14ARF tumor suppressor genes and is frequently co-deleted with p16INK4a in many cancers. Deletion of MTAP has been reported to create a reliance of MTAP tumors on de novo purine synthesis to maintain adequate p...

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 ...

To clarify the contributions of amidophosphoribosyltransferase (ATase) and its feedback regulation to the rates of purine de novo synthesis, DNA synthesis, protein synthesis, and cell growth, mutated human ATase (mhATase) resistant to feedback inhibition by purine ribonucleotides was engineered by site-directed mutagenesis and expressed in CHO ade (-)A cells (an ATase-deficient cell line of Chi...

Indole and indolizines (heterocyclic aromatic compounds structurally and chemically isomeric with indoles) are an important class of N-fused heterocyclic compounds due to their interesting biological and optical properties. Different strategies for generating di‐ verse collections of small molecules with indole and indolizine moieties have been de‐ veloped. They can be synthesized by means of c...

Rates of purine salvage of adenine and hypoxanthine into the adenine nucleotide (AdN) pool of the different skeletal muscle phenotype sections of the rat were measured using an isolated perfused hindlimb preparation. Tissue adenine and hypoxanthine concentrations and specific activities were controlled over a broad range of purine concentrations, ranging from 3 to 100 times normal, by employing...