1. A strain of Ehrlich ascites-tumour cells that showed little inhibition of growth in the presence of 6-mercaptopurine accumulated less than 5% as much 6-thioinosine 5'-phosphate in vivo, in the presence of 6-mercaptopurine, as did the sensitive strain from which it was derived. 2. Specific activities of the phosphoribosyltransferases that convert adenine, guanine, hypoxanthine and 6-mercaptop...

Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder manifesting as urolithiasis or crystalline nephropathy. It leads to the generation of large amounts of poorly soluble 2,8-dihydroxyadenine excreted in urine, yielding kidney injury and in some patients, kidney failure. Early recognition of the disease, institution of xanthine analog therapy to block the formatio...

1. The hepatic metabolism of hypoxanthine was investigated by studying both the fate of labelled hypoxanthine, added at micromolar concentrations to isolated rat hepatocyte suspensions, and the kinetic properties of purified hypoxanthine/guanine phosphoribosyltransferase from rat liver. 2. More than 80% of hypoxanthine was oxidized towards allantoin; less than 5% of the label was incorporated i...

The characteristics of adenine, guanine, hypoxanthine, xanthine, and uracil uptake in Escherichia coli B show that each base is transported by a specific system. The data support the concept that the transport of guanine, hypoxanthine, xanthine, and uracil function without direct involvement of the respective purine or pyrimidine phosphoribosyltransferase enzymes. Uracil phosphoribosyltransfera...

The ability of rel+ cell strains of Escherichia coli to take up nucleosides and bases and convert them to the corresponding ribonucleoside 5’-triphosphates is qualitatively dependent upon amino acids, much the same as the ability to accumulate RNA. Restriction of uptake in this case occurs under the same conditions that elicit guanosine 5’-diphosphate, 2’or 3’-diphosphate (ppGpp) accumulation a...

Background: Oral squamous cell carcinoma is a major cause of cancer-related deaths world-wide. Histologically it arises from the benign squamous epithelium lining the oral cavity and is conventionally divided into well, moderate, and poorly differentiated subtypes. Nicotinamide phosphoribosyltransferase catalyses the rate-limiting step of nicotinamide adenine dinucleotide synthesis and is highl...

Purine metabolism has been examined in a clonal line of mouse neuroblastoma cells resistant to the cytotoxic effects of 6-thioguanine. Comparative studies in the resistant and parental lines indicate that the former cells have less than 1% of normal hypoxanthine phosphoribosyltransferase (EC 2.4.2.8) activity. The activities of other enzymes important in the de novo and salvage pathways of puri...

Some of the factors responsible for the control of pyrimidine nucleotide biosynthesis in intact cells have been investigated using rat hepatoma cells grown in continuous culture. The addition of uridine (0.5 mM) to culture medium causes a decrease of approximately 70% in the rate of de nouo pyrimidine nucleotide biosynthesis, as determined by incorporation of WO 2. Maximum inhibition of W02 inc...