Borrelia burgdorferi is the tick-borne bacterium that causes the multistage inflammatory disease Lyme disease. B. burgdorferi has a reduced genome and lacks the enzymes required for de novo synthesis of purines for synthesis of RNA and DNA. Therefore, this obligate pathogen is dependent upon the tick vector and mammalian host environments for salvage of purine bases for nucleic acid biosynthesi...

The purine anti-metabolite 6-mercaptopurine is one of the most widely used drugs for the treatment of acute childhood leukemia and chronic myelocytic leukemia. Developed in the 1950s, the drug is also being used as a treatment for inflammatory diseases such as Crohn's disease. The antiproliferative mechanism of action of this drug and other purine anti-metabolites has been demonstrated to be th...

BACKGROUND Whether myocardial ATP content falls in heart failure is a long-standing and controversial issue. The mechanism(s) to explain any decrease in ATP content during heart failure have not been identified. METHODS AND RESULTS Cardiac dysfunction, heart failure, and a prolonged steady state of heart failure were induced by chronic right ventricular pacing for 1 to 2 weeks, 3 to 4 weeks, ...

Love, Samuel H. (Bowman Gray School of Medicine, Wake Forest College, Winston-Salem, N.C.), and Charles N. Remy. Metabolism of methylated purines in Escherichia coli: derepression of purine biosynthesis. J. Bacteriol. 91:1037-1049. 1966.-Various methylated purines were examined for their effects on growth of purine-requiring mutants of Escherichia coli, strains W-11 and B-96, and for their effe...

Feedback inhibition of biosynthetic pathways in animal cells may be investigated at three levels of complexity. (a) Enzymological studies may evaluate the relative sensitivity of various enzymes of the pathway to inhibition by end products, the relative inhibitory potencies of different end products, and the mode of interaction of inhibitors and enzymes. In the absence of other information, how...

In the development of the mature rabbit erythrocyte from the reticulocyte, the capacity for the synthesis de novo of the purine ring in vitro is lost (2, 3). The mature rabbit erythrocyte, however, does retain a portion of the biosynthetic pathway de novo, as evidenced by its utilization of 5-amino-1-ribosylWimidazolecarboxamide and sodium formate-Cl4 for the formation of inosinic acid (4). The...

In tropical legumes like Glycine, Phaseolus and Vigna sp., ammonia as direct product of symbiotic nitrogen fixation is converted to ureides (allantoin and allantoic acid) and they were translocated to the shoots as nitrogen source. In the xylem sap of soybean in reproductive phase the ureides reached to 60-75% of soluble nitrogen. In nodules infected cells (plastid and mitochondria) and uninfec...

5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR) is an activator of AMP activated protein kinase (AMPK) and a regulator of de novo purine synthesis. There are several earlier reports indicating that AICAR treatment suppresses cell growth via regulation of AMPK or de novo purine synthesis. We found cell growth to be suppressed by AICAR treatment in HepG2 because of p53 accumulation...

Addition of purines to the growth medium of Escherichia coli represses synthesis of cytosine deaminase (codA) and enzymes of purine de novo synthesis. After Tn10 mutagenesis, mutants displaying derepressed levels of cytosine deaminase in the presence of hypoxanthine were isolated. One of these had simultaneously acquired resistance to the hypoxanthine analog 6-mercaptopurine. The mutation purR6...

The drugs in clinical use against African sleeping sickness are toxic, costly, or inefficient. We show that Trypanosoma brucei, which causes this disease, has very low levels of CTP, which are due to a limited capacity for de novo synthesis and the lack of salvage pathways. The CTP synthetase inhibitors 6-diazo-5-oxo-l-norleucine (DON) and alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid...