Purine nucleotide reutilization by human lymphoblast lines with aberrations of the inosinate cycle.
نویسندگان
چکیده
A purine nucleotide (inosinate) cycle is demonstrated with human lymphoblasts. The lymphoblast requires approximately 50 nmol of purine/10(6) cell increment. When the inosinate cycle is interrupted by the genetic, severe deficiency of either or both purine nucleoside phosphorylase (PNP) or hypoxanthine phosphoribosyltransferase (HPRT), purine accumulates in the culture medium as inosine, guanosine, deoxyinosine, and deoxyguanosine (PNP deficiency or PNP, HPRT deficiency) or hypoxanthine and guanine (HPRT deficiency). This accumulation represents an additional 25 to 32 nmol of purine which must be synthesized per 10(6) cell increment. PNP-deficient lymphoblasts have PPRibP contents characteristic of normal lymphoblasts, about 20 to 25 pmol/10(6) cells. HPRT-deficient lymphoblasts have four times higher PPRibP contents. The lymphoblast deficient for both PNP and HPRT has only a marginal elevation of PPRibP content, 1.5 times normal values. The elevated PPRibP content of HPRT-deficient cells reflects the efficient, unilateral reutilization of the ribose moiety of purine ribonucleotides and is not a cause of purine overproduction. Purine overproduction characterizing PNP-deficient lymphoblasts appears similar to overproduction from deficiency of HPRT, i.e. a break in the inosinate cycle rather than overactive de novo purine synthesis.
منابع مشابه
Selective expression of phosphoribosylpyrophosphate synthetase superactivity in human lymphoblast lines.
Phenotypic expression of 5-phosphoribosyl 1-pyrophosphate (PRPP) synthetase superactivity was examined in lymphoblast lines derived from six unrelated male patients. Fibroblasts from these individuals have increased rates of PRPP and purine nucleotide synthesis and express four classes of kinetic derangement underlying enzyme superactivity: increased maximal reaction velocity (catalytic defect)...
متن کاملInhibition of Furine Nucleotide Metabolism by 6-Methylthiopurine Ribonucleoside and Structurally Related Compounds1
6-Methylthiopurine ribonucleoside was found to inhibit nucleotide formation from hypoxanthine and aminoimidazole carboxamide in Ehrlich ascites tumor cells in vitro and to inhibit inosinate dehydrogenase activity in intact cells. These effects are produced at higher drug concentrations than required to inhibit purine biosynthesis de novo. 4-Methylthio-7-|8-D-ribofuranosyl pyrrolo[2,3-i/]pyrimid...
متن کاملMutations induced at the hypoxanthine-guanine phosphoribosyltransferase locus of human T-lymphoblasts by perturbations of purine deoxyribonucleoside triphosphate pools.
Chronic perturbations of intracellular deoxyribonucleoside triphosphate (dNTP) pools have been associated with a mutator phenotype and increased mutation rates at several genetic loci. We have examined the specific effects of transient pharmacological purine dNTP pool perturbations on mutations induced at the hypoxanthine-guanine phosphoribosyltransferase (HPRT) locus in a cultured human T-lymp...
متن کاملفراوانی آسیبهای کروموزومی ناشی از داروی بلئومایسین سولفات در سلولهای هیبریدومای F3B6 و HF2x653 در مقایسه با سلولهای غیرهیبرید والدی
Background and Objective: Hybrid cells are made from fusion of two or more somatic cells. After formation chromosomes are located in one membrane . . So nucleic condition of each fused cell has changes and two genomes and chromosomes interact with each other. Locating the genes in new nucleic and cytoplasmic condition and great chromosomal rearrangement in these new formed cells can affect th...
متن کاملInduction of chromosomal aberrations in human primary fibroblasts and immortalized cancer cells exposed to extremely-low-frequency electromagnetic fields
Background: Rapidly increasing possibilities of exposure to environmental extremely low-frequency electromagnetic fields (ELF-EMF) have become a topic of worldwide investigation. Epidemiological and laboratory studies suggest that exposure to ELF-EMF may increase cancer risk therefore assessment of chromosomal damage in various cell lines might be of predictive value for future risk es...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- The Journal of biological chemistry
دوره 259 7 شماره
صفحات -
تاریخ انتشار 1984