Nucleic acids, turnover

The so-called salvage pathways are available in many cells to scavenge free purine and pyrimidine bases, nucleosides, and mononucleotides and to convert these to metabolically useful di- and trinucleotides. The function of these pathways is to avoid the costly (energy) and lengthy de novo purine and pyrimidine biosynthetic processes. In some cells, in fact, the salvage pathways yield a greater quantity of nucleotides than the de novo pathways. The substrates for salvage reactions may come from dietary sources or from normal nucleic acid turnover processes. 

Increased nucleic acid turnover (e.g., leukemia, myeloma, radiotherapy, chemotherapy, trauma)... 

Secondary gout is a result of hyperuricemia attributable to several identifiable causes. Renal retention of uric acid may occur in acute or chronic kidney disease of any type or as a consequence of administration of drugs diuretics, in particular, are implicated in the latter instance. Organic acidemia caused by increased acetoacetic acid in diabetic ketoacidosis or by lactic acidosis may interfere with tubular secretion of urate. Increased nucleic acid turnover and a consequent increase in catabolism of purines may be encountered in rapid proliferation of tumor cells and in massive destruction of tumor cells on therapy with certain chemotherapeutic agents. 

Feigelson, R, Feigelson, M., and Fancher, C., Kinetics of liver nucleic acid turnovers during enzyme induction in the rat, Biochim. Biophys. Acta, 32, 133, 1959. 

Increased dietary Intake Increased nucleic acid turnover Increased ATP breakdown... 

These results are apparently irreconcilable with other studies that show that when xanthine oxidase activity does increase above normal (e.g., in tumor-bearing rats, vitamin E deficiency, and some virus infections) there is always a proportionate increase in allantoin excretion. This increase may be as much as tenfold and is too great to be accounted for by increased nucleic acid turnover under these conditions. Xanthine oxidase activity also increases upon refeeding after starvation, and this has been shown to be due to new RNA and protein synthesis SI). These results raise questions concerning intracellular compartmentation, enzyme latentiation, etc., that have yet to be answered. 

Within the cell, the stabilizing effect of polyamines on nucleic add structures plays a rdle in the control of nucleic acid turnover, and DNA transcxiptioiL However. polyamines are also fixed on other cell structures bearing addic groups, mainly on the cell-membrane, and many of the polyamines effects can be attributed to a stabilization of the membrane, or a modification of its permeal ty. 

Fohc acid is a precursor of several important enzyme cofactors required for the synthesis of nucleic acids (qv) and the metaboHsm of certain amino acids. Fohc acid deficiency results in an inabiUty to produce deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and certain proteins (qv). Megaloblastic anemia is a common symptom of folate deficiency owing to rapid red blood cell turnover and the high metaboHc requirement of hematopoietic tissue. One of the clinical signs of acute folate deficiency includes a red and painhil tongue. Vitamin B 2 folate share a common metaboHc pathway, the methionine synthase reaction. Therefore a differential diagnosis is required to measure foHc acid deficiency because both foHc acid and vitamin B 2 deficiency cause... 

Gonsky R et al. Identification of rapid turnover transcripts overexpressed in thyroid tumors and thyroid cancer cell lines use of a targeted differential RNA display method to select for mRNA subsets. Nucleic Acids Res 1997 25 3823-3831. 

Enzymes useful for detection purposes in ELISA techniques (Chapter 26) also can be employed in the creation of highly sensitive DNA probes for hybridization assays. The attached enzyme molecule provides detectability for the oligonucleotide through turnover of substrates that can produce chromogenic or fluorescent products. Enzyme-based hybridization assays are perhaps the most common method of nonradioactive detection used in nucleic acid chemistry today. The sensitivity of enzyme-labeled probes can approach or equal that of radiolabeled nucleic acids, thus eliminating the need for radioactivity in most assay systems. 

Abstract This chapter updates but mostly supplements the author s Ange-wandte Review,111 setting in context recent advances based on protein and nucleic acid engineering. Systems qualify as a true enzyme mimics if there is experimental evidence for both the initial binding interaction and catalysis with turnover, generally in the shape of saturation kinetics. They are discussed under five broad headings mimics based on natural enzymes, on other proteins, on other biopolymers, on synthetic macromolecules and on small-molecule host-guest interactions. 

Digestion of endogenous nucleic acids (cell death, RNA turnover)... 

Adenosine deaminase (ADA) is a ubiquitous enzyme that is essential for the breakdown of the purine base adenosine, from both food intake and the turnover of nucleic acids. ADA hydrolyzes adenosine and deoxyadenosine into inosine and deoxyinosine, respectively, via the removal of an amino group. Deficiency of the ADA enzyme results in the build-up of deoxyadenosine and deoxyATP (adenosine triphosphate), both of which inhibit the normal maturation and survival of lymphocytes. Most importantly, these metabolites affect the ability of T-cells to differentiate into mature T-cells [656430], [666686]. ADA deficiency results in a form of severe combined immunodeficiency (SCID), known as ADA-SCID [467343]. 

Uric acid is the excreted end product of purine catabolism in primates, birds, and some other animals. A healthy adult human excretes uric acid at a rate of about 0.6 g/24 h the excreted product arises in part from ingested purines and in part from turnover of the purine nucleotides of nucleic acids. In most mammals and many other vertebrates, uric acid is further degraded to al-lantoin by the action of urate oxidase. In other organisms the pathway is further extended, as shown in Figure 22-45. 

In this chapter we examine the synthesis of RNA on a DNA template and the postsynthetic processing and turnover of RNA molecules. In doing so we encounter many of the specialized functions of RNA, including catalytic functions. Interestingly, the substrates for RNA enzymes are often other RNA molecules. We also describe systems in which RNA is the template and DNA the product, rather than vice versa. The information pathways thus come full circle, revealing that template-dependent nucleic acid synthesis has standard rules... 

Purines that result from the normal turnover of cellular nucleic acids, or that are obtained from the diet and not degraded, can be reconverted into nucleoside triphosphates and used by the body. This is referred to as the "salvage pathway" for purines. 

Phase I and II clinical trials indicated that acronycine reduced pain of the spine in some patients with multiple myeloma [280,282,283]. Acronycine has been reported to cause leukopoenia and to have CNS-depressant activity [284], Biochemically, acronycine inhibits incorporation of extracellular nucleosides into the RNA and DNA of leukaemia L-5178Y cell culture. There is, however, no evidence of interaction between acronycine and DNA or inhibition of template activity of DNA. This alkaloid does not inhibit nucleic acid synthesis in the cell, but rather inhibits the accumulation of extracellular uridine or thymidine, as nucleotides, in the intracellular precursor pool [285, 286], Acronycine, acting primarily on membranous organelles [287], seems to interfere with the structure, function and/or turnover of cell membrane components, thereby changing the fluidity of the plasma membrane [288]. 

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