Adenine alteration

No living cells can store large amounts of ATP. There is a finite amount of adenine distributed between AMP, ADP and ATP. Thus if the cell has a relatively high concentration of ATP, the concentrations of AMP and/or ADP must be lowered. The balance alters like a "see-saw", as one goes up the other must come down. In addition the total amount of NAD+/NADH and NADP+/NADPH in the cell is constant... 

Hitti, E., Iakovleva, T., Brook, M., Deppenmeier, S., Gruber, A. D., Radzioch, D., Clark, A. R., Blackshear, P. J., Kotlyarov, A., and Gaestel, M. (2006). Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor mRNA stability and translation mainly by altering tristetraprolin expression, stability, and binding to adenine/uridine-rich element. Mol. Cell Biol. 26, 2399—2407. 

When cyanide blocks oxidative metabolism in mitochondria, cells shift their metabolism and enhanced glucose utilization occurs. One consequence of this altered metabolic pattern is accumulation of nicotinamide adenine dinucleotide (NADH). NADH is a powerful stimulant of calcium mobilization from cell stores through "inositol triphosphate receptors." Elevated calcium damages cells. Increase in cellular NADH, therefore, is an important event in the toxic action of cyanide (Kaplin et al. 1996). 

For the 13 hammerhead FIFI16 mutants prepared by the reference 41 researchers, cleavage activity was significantly reduced in all cases. In four cases, at positions C3, A9, Gio.i, and A13, addition of the correct base (U, A, G, or C) rescued the activity of the ribozyme. A9X, for instance, is a ribozyme where the adenine base at position 9 has been removed to generate an abasic nucleotide (X = a nucleotide in which H substitutes for the removed base—see Figure 6.14). This altered ribozyme exhibited a 4 x 10 times lower catalytic rate than that for the wild-type ribozyme (krei = = 0.0004). When... 

There are several antitumor antibiotics resembling the synthetic nucleoside antimetabolites discussed on p. 160. They are adenine derivatives with unusual furanose compounds attached to the 9-position. Psicofuranine (54) is an example. The rather more complex example puromycin (55) is also active against trypanosomes and Gram-positive bacteria. Tubercidin (56) and two related antibiotics have an altered purine system. 

Figure 15-7 The flavin coenzymes flavin adenine dinucleotide (FAD) and riboflavin 5 -phosphate (FMN). Dotted lines enclose the region that is altered upon reduction.

Many compounds have been tested simultaneously with (2-chloroethyl)tri-methylammonium chloride on Thatcher wheat, to ascertain, if possible, whether these chemicals were affecting a particular metabolic process. Other cholinesterase inhibitors such as eserine, diisopropyl fluorophosphate, and nitrogen mustard, neither negated the effect from (2-chloroethyl)trimethylammonium chloride nor altered the growth of the plant themselves. Many other substances were also without effect on the action of (2-chloroethyl)trimethylammonium chloride. A very slight reversal of the alteration by (2-chloroethyl)trimethylam-monium chloride was obtained by 10 2 and 10 3 M choline, betaine, and adenine. Only gibberellin completely and rapidly reversed the shorter growth pattern of a plant which had been treated with (2-chloroethyl)trimethylammonium chloride. 

Rhaese H -J (1968) Chemical analysis of DNA alterations III. Isolation and characterization of adenine oxidation products obtained from oligo- and monodeoxyadenylic acids treated with hydroxyl... 

DNA isolated from cells (Kessel et al., 2002) and tissues and urine of animals (Vijayaraghavan et al., 2001 Yamanaka et al., 2001) treated with arsenic show lesions induced by oxidative stress. These lesions include 8-oxo-2 -deoxyguanosine and 8-hydroxy-2 -deoxyguanosine. These DNA lesions may lead to base-pair substitutions (guanine to thymidine and adenine to cytosine) during DNA synthesis, which could lead to altered gene products. 

To understand the biochemistry of mutagenesis, it is important to recall from Chapter 3 that DNA contains the nitrogenous bases adenine, guanine, cytosine, and thymine. The order in which these bases occur in DNA determines the nature and structure of newly produced ribonucleic acid (RNA), a substance produced as a step in the synthesis of new proteins and enzymes in cells. Exchange, addition, or deletion of any of the nitrogenous bases in DNA alters the nature of RNA produced and can change vital life processes, such as the synthesis of an important enzyme. This phenomenon, which can be caused by xenobiotic compounds, is a mutation that can be passed on to progeny, usually with detrimental results. 

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