Nucleic acid formation

The pentose phosphate pathway is an alternative route for the metabolism of glucose. It does not generate ATP but has two major functions (1) The formation of NADPH for synthesis of fatty acids and steroids and (2) the synthesis of ribose for nucleotide and nucleic acid formation. Glucose, fructose, and galactose are the main hexoses absorbed from the gastrointestinal tract, derived principally from dietary starch, sucrose, and lactose, respectively. Fructose and galactose are converted to glucose, mainly in the liver. 

The above-mentioned facts require that ribose must have undergone further reactions immediately after its formation under prebiotic conditions. More than 20 years ago R. Shapiro (1984) pointed out the immense problems which would have needed to be solved in prebiotic nucleic acid formation. 

Two points thus argue against the participation of ribose in nucleic acid formation the lability of the molecule and the problems with its synthesis (the concentrations of the starting materials are too high). Other, newer and more effective syntheses seem necessary, whereby prebiotic conditions (although these are not known precisely) strongly limit the possibilities. 

In shows selective toxicity to anaerobic microorganisms, where it is converted to active form by reduction of its nitro group and this gets bound to DNA and prevent nucleic acid formation. 

Niacin, a water-soluble vitamin vital for oxidation by living cells, functions in the body as a component of two important coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are involved in the release of energy from carbohydrate, fat, and protein, and in the synthesis of protein, fat, and pentoses for nucleic acid formation. Milk is a poor source of preformed niacin, containing about 0.08 mg per 100 g. However, milk s niacin value is considerably greater than indicated by its niacin content (Horwitt et al. 1981). Not only is the niacin in milk fully available, but the amino acid tryptophan in milk can be used by the body for the synthesis of niacin. For every 60 mg of tryptophan consumed, the body synthesizes 1 mg of niacin. Therefore, the niacin equivalents in 100 g milk equal 0.856 mg including that from pre-... 

Unfortunately, there are few pure examples of true selective toxicity. Perhaps the best is penicillin. The therapeutic specificity of this antibiotic is based upon the qualitative difference between bacterial cell wall synthesis and mammalian cell membrane synthesis. Synthesis of the former can be inhibited by penicillin while the latter is unaffected. Thus, penicillin is one of the few examples of a drug that can actually cure an illness. A similar example involves the sulfa drugs, which interfere with the synthesis of folic acid, used in nucleic acid formation, in bacteria. While bacteria must synthesize their own folic acid, mammalian cells utilize dietary, preformed folic acid and are not susceptible to interference with its formation. 

Cyanocobalamine is a component of several coenzymes and has an effect on nucleic acid formation through its action in cycling 5-methyl-tetrahydrofolate back into the folate pool. The most important dietary sources of the vitamin are animal products. Vitamin Bl2 is also produced by many microorganisms. It is not surprising that vitamin B12 deficiency of dietary origin only occurs in vegetarians. 

Several examples of prodrugs are found in the purine and pyrimidine analogs that substitute for natural nucleotides and inhibit nucleic acid formation. For example, 5-fluorouracil is essentially harmless to mammalian host and tumor cells. Upon administration, the drug is subject to one of two opposingmetabolicfates (10). Inactivation and elimination are accomplished by catabolism (about 80% of the dose) and by urinary excretion of unchanged drug... 

Investigations to elucidate the formation of higher-order nucleic acid structures were also done by Wang et al. [68]. Triple-helical nucleic acid formation in solution, in particular C GC and G GC, followed by immobilization of the nucleic acid complex onto electrode surfaces of mercury and carbon paste was elucidated by reductions in the magnitude of the guanine oxidation peak and disappearance of a... 

The complexities of the intact animal have made it difficult to arrive at any clear-cut generalizations regarding the metabolism of bases and related compounds. Some suggestions are offered below regarding the apparent influence of certain enzymes on nucleic acid formation from labeled preformed purine compounds. 

A study of the mechanism of uracil incorporation into uridine phosphates was carried out in the Ehrlich ascites tumor, a tissue which utilized uracil as well as small molecule precimsors for nucleic acid formation (312). Uridine 5 -phosphate (UMP) was formed from uracil, ATP, and ribose 1-phosphate (R-l-P). Uridine was an intermediate in the formation of the nucleotide and was formed by the reaction of uracil and R-l-P with pyrimidine nucleoside phosphorylase (313, 314). Nucleoside kinase reacted the nucleoside with ATP to form UMP. The sequence is ... 

The addition of purines and pyrimidines accelerates the rate of protein synthesis in washed Staph, aureus as shown above. If penicillin in high concentrations is added to the incubation mixture, the additional protein synthesis due to the presence of purines and pyrimidines is abolished, although the basal protein synthesis is not significantly affected, as shown in Fig. 29. This effect is accompanied by a decrease in the purine-stimulated nucleic acid formation, but the concentration of penicillin which abolishes the additional protein synthesis does no more than halve (and frequently less than halve) the additional nucleic acid synthesis. Estimation of the proportions of the purine and pyrimidine bases in the nucleic acid fraction by the method of Smith and Markham (1950) modified by Wyatt (1951) shows that the changes lie in the ribonucleic acid fraction and that there is no significant alteration in the proportions of the various bases whether penicillin is present or not (Gale and Folkes, 1953b). 

In experiments with rats with two inoculated sarcomata, one sarcoma was irradiated while the other was effectively shielded. A reduction of labeled nucleic acid formation was found to take place in both the reduction was smaller in the shielded than in the irradiated sarcoma (4, see also 5). 

In 1971 the Protein Data Bank - PDB [146] (see Section 5.8 for a complete story and description) - was established at Brookhaven National Laboratories - BNL -as an archive for biological macromolccular cr7stal structures. This database moved in 1998 to the Research Collaboratory for Structural Bioinformatics -RCSB. A key component in the creation of such a public archive of information was the development of a method for effreient and uniform capture and curation of the data [147], The result of the effort was the PDB file format [53], which evolved over time through several different and non-uniform versions. Nevertheless, the PDB file format has become the standard representation for exchanging inacromolecular information derived from X-ray diffraction and NMR studies, primarily for proteins and nucleic acids. In 1998 the database was moved to the Research Collaboratory for Structural Bioinformatics - RCSB. 

PDB files were designed for storage of crystal structures and related experimental information on biological macromolecules, primarily proteins, nucleic acids, and their complexes. Over the years the PDB file format was extended to handle results from other experimental (NM.R, cryoelectron microscopy) and theoretical methods... 

Nucleic acid contents of SCP products, which range up to 16% in bacteria and 6—11% in yeasts, must be reduced by processing so that intakes are less than 2 g/d to prevent kidney stone formation or gout. Adverse skin and gastrointestinal reactions have also been encountered as a result of human consumption of some SCP products (87). 

The emission yield from the horseradish peroxidase (HRP)-catalyzed luminol oxidations can be kicreased as much as a thousandfold upon addition of substituted phenols, eg, -iodophenol, -phenylphenol, or 6-hydroxybenzothiazole (119). Enhanced chemiluminescence, as this phenomenon is termed, has been the basis for several very sensitive immunometric assays that surpass the sensitivity of radioassay (120) techniques and has also been developed for detection of nucleic acid probes ia dot-slot. Southern, and Northern blot formats (121). 

The first are competitors of PABA (p-aminobenzoic acid) and thus intermpt host de novo formation of the tetrahydrofoUc acid required for nucleic acid synthesis. Examples of dmgs that fall into this group are the sulfones and sulfonamides. The most weU-known of the sulfones is dapsone (70, 4,4 -diaminodiphenyl sulfone, DDS), whose toxicity has discouraged its use. Production of foHc acid, which consists of PABA, a pteridine unit, and glutamate, is disturbed by the substitution of a sulfonamide (stmcturally similar to PABA). The antimalarial sulfonamides include sulfadoxine (71, Fanasd [2447-57-6]) sulfadiazine (25), and sulfalene (72, sulfamethoxypyrazine [152-47-6] Kelfizina). Compounds of this group are rapidly absorbed but are cleared slowly. 

VMD is designed for the visualization and analysis of biological systems such as proteins, nucleic acids, and lipid bilayer assemblies. It may be used to view more general molecules, as VMD can read several different structural file formats and display the contained structure. VMD provides a wide variety of methods for rendering and coloring a molecule. VMD can be used to animate and analyze the trajectory of a molecular dynamics (MD) simulation. 

Nucleic acids in the DNA contain a high number of nucleophilic sites that can be attacked by electrophilic intermediates (metabolites) of chemical compounds. DNA adducts formed may cause alterations in the expression of a critical gene in the cell and thus lead to cell death. For example, modification of p53 tumor suppressor gene may inactivate the functions of the p53 protein and render cells sensitive to malignant transformation. Also, formation of RNA adducts may inhibit key cellular events because RNA is essential for protein synthesis. 

FIGURE 1.9 (a) Amino acids build proteins by connecting the n-carboxyl C atom of one amino acid to the n-amino N atom of the next amino acid in line, (b) Polysaccharides are built by combining the C-1 of one sugar to the C-4 O of the next sugar in the polymer, (c) Nucleic acids are polymers of nucleotides linked by bonds between the 3 -OH of the ribose ring of one nucleotide to the 5 -P04 of its neighboring nucleotide. All three of these polymerization processes involve bond formations accompanied by the elimination of water (dehydration synthesis reactions). 

Nucleic acids are linear polymers of nucleotides linked 3 to 5 by phosphodi-ester bridges (Figure 11.17). They are formed as 5 -nucleoside monophosphates are successively added to the 3 -OH group of the preceding nucleotide, a process that gives the polymer a directional sense. Polymers of ribonucleotides are named ribonucleic acid, or RNA. Deoxyribonucleotide polymers are called deoxyribonucleic acid, or DNA. Because C-1 and C-4 in deoxyribonucleotides are involved in furanose ring formation and because there is no 2 -OH, only... 

The possibility of interfering with the structure or formation of nucleic acids with the aid of such antimetabolites obviously has great practical significance. An interference with growth of neoplastic tissue and influence on the genetic properties of an organism should be mentioned in the first place. 

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