Schistosoma mansoni do not have de novo purine pathways and rely on purine salvage for their purine supply. It has been demonstrated that, unlike humans, the S. mansoni is able to produce adenine directly from adenosine, although the enzyme responsible for this activity was unknown. In the present work we show that S. mansoni 5´-deoxy-5´-methylthioadenosine phosphorylase (MTAP, E.C. 2.4.2.28) i...

TraiH-tamoxifen (TAM) has been used successfully in therapy for estrogen-dependent human breast tumors and prevention of their recur rence. The mechanism of this prevention was thought to be due to the interference of TAM with estrogen promotion. TAM has a wider anticarcinogenic action that is similar to other chemopreventive agents in that it suppresses tumor promotion in 2-stage carcinogenesi...

Editors-in-Chief: SIDNEY P. COLOWICK and NATHAN 0. KAPLAN VOLUME 51: PURINE AND PYRIMIDINE NUCLEOTIDE METABOLISM Edited by PATRICIA A. HOFFEE and MARY ELLEN JONES Surveying the last decade's significant advances conSECTION HEADINGS: BIOSYNTHETIC ENZYMES. Activacerning the enzymology of purine and pyrimidine metabotion of Ribose Phosphate. De Novo Pyrimidine Biosynthelism and the development of ...

Schistosomiasis, a disease caused by the trematodes of the Schistosoma genus, affects about 240 million people worldwide. The Praziquantel (PZQ) is the drug used to treat this disease. However, reports of resistant strains reinforce the need to develop a new schistosomicidal drug. The study of new drugs and vaccines that can contribute to the control of this pathology becomes urgent. A new appr...

The enzyme methylthioadenosine phosphorylase functions in both purine and polyamine metabolism is dividing mammalian cells. To determine the effects of the loss of this enzyme on cell growth and metabolism, we selected two methylthioadenosine phosphorylase-deficient mutant clones of the transplantable murine T lymphoma cell line R1.1. The first had 3.5% of wild type methylthioadenosine phosphor...

The enzymes of the de novo purine biosynthetic pathway have been partially co-purified from pigeon liver by a method dependent upon the use of the nonionic polymer polyethylene glycol for enzyme stabilization and cofractionation. Although the enzymes did not appear to constitute a large macromolecular complex it was evident that some particular inter-relationship between them was preserved duri...

Gout is classed among the inborn errors of metabolism,1 but unlike the majority of such disorders no single specific metabolic defect has yet been found to account for the hyperuricemia characteristic of this disease.2 Although impaired renal excretion of uric acid is responsible for the hyperuricemia of some patients, an increased rate of purine biosynthesis de novo contributes to the hyperuri...

The enzymes in the human de novo purine synthesis pathway were found to form a cellular complex, the purinosome, upon culturing cells in purine-depleted medium (An, S., Kumar R., Sheets, E. D., and Benkovic, S. J. (2008) Science 320, 103-106). Purinosome formation and dissociation were found to be modulated by several factors, including the microtubule network and cell signaling involving prote...

Genetic analyses have suggested that the pyrimidine moiety of thiamine can be synthesized independently of the first enzyme of de novo purine synthesis, phosphoribosylpyrophosphate amidotransferase (PurF), in Salmonella typhimurium. To obtain biochemical evidence for and to further define this proposed synthesis, stable isotope labeling experiments were performed with two compounds, [2-13C]glyc...

6-Thioguanine (3) has been shown to inhibit a wide spectrum of neoplasms. Its anti-tumor prop erties are markedly potentiated when combined with azaserine, an inhibitor of the synthesis de novo of purines (10, 13). One of these reports also indicated that, for maximum effect, the antimetabolites had to be administered simultaneous ly. These results suggest that thioguanine inter feres with some...