The mature rabbit erythrocyte has been shown to be incapable of synthesizing de novo the purine portions of adenosine triphosphate and of guanosine triphosphate, in vitro (2). It is able, however, to carry out the final steps of this pathway from sodium formate and 5-amino-1-ribosyl-4-imidazolecarboxamide, a finclmg which suggests that a portion of the over-all enzymatic sequence is lost during...

Drosophila melanogaster purine auxotrophs ade2(1) and ade3(1) have been characterized biochemically. The ade2(1) strain is deficient in the fourth step of the de novo purine synthetic pathway catalyzed by phosphoribosylglycinamidine synthase (phosphoribosylformylglycinamide amidotransferase). The ade3(1) strain is deficient in the previous step catalyzed by phosphoribosylglycinamide formyltrans...

Endothelial cells are known to be metabolically rather robust. To study the mechanisms involved, porcine aortic endothelial cells (PAEC), cultured on microcarrier beads, were perfused with glucose (10 mM) or with substrate-free medium. Substrate-free perfusion for 2 h induced an almost complete loss of nucleoside triphosphates (31P-NMR) and decreased heat flux, a measure of total energy turnove...

The reversible association and dissociation of a metabolic multi-enzyme complex participating in de novo purine biosynthesis, the purinosome, was demonstrated in live cells to respond to the levels of purine nucleotides in the culture media. We also took advantage of in vitro proteomic scale studies of cellular substrates of human protein kinases (e.g. casein kinase II (CK2) and Akt), that impl...

The mature rabbit erythrocyte has been shown to be incapable of synthesizing de novo the purine portions of adenosine triphosphate and of guanosine triphosphate, in vitro (2). It is able, however, to carry out the final steps of this pathway from sodium formate and 5-amino-1-ribosyl-4-imidazolecarboxamide, a finclmg which suggests that a portion of the over-all enzymatic sequence is lost during...

The enzymic capacities of the de novo and the salvage pathways for purine nucleotide synthesis were compared in rat in normal, differentiating, and regenerating liver, and in three hepatomas of widely different growth rates. The activities of the key de novo and salvage enzymes were also determined in mouse lung and Lewis lung carcinoma, in human kidney and liver, and in renal cell carcinoma an...

Thioguanine and mercaptopurine are prodrugs requiring conversion into thiopurine nucleotides to exert cytotoxicity. Thiopurine S-methyltransferase (TPMT), an enzyme subject to genetic polymorphism, catabolizes thiopurines into inactive methylated bases, but also produces methylthioguanine nucleotides and methylmercaptopurine nucleotides from thioguanine and mercaptopurine nucleotides, respectiv...

The aim of this study was to investigate the influence of folylpolyglutamyl synthetase (FPGS) activity on the cellular pharmacology of the classical antifolates raltitrexed and methotrexate (MTX) using two human leukemia cell lines, CCRF-CEM and CCRF-CEM:RC2Tomudex. Cell growth inhibition and drug-induced inhibition of de novo thymidylate and purine biosynthesis were used as measures of the cel...

besides being a metabolite of nucleotides like atp, adenosine is a mediator of neuronal function in the central nervous system. its actions are mediated by at least three extracellular receptors. in this review different aspects of adenosine such as biosynthesis, release, inactivation and its receptors are discussed. it also covers pre- and postsynaptic effects as well as postreceptor mechanism...