Protein and DNA Synthesis

When the cell requires instructions for protein production, part of the code on DNA, starting at an initiator and ending at a stop codon, is converted into a more mobile form by transferring the DNA code into a matching RNA code on a messenger ribonucleic acid (mRNA), a process known as transcription. The decoding, or translation, of mRNA then takes place by special transfer ribonucleic acids (tRNA), which recognize individual codons as amino acids. The sequence of amino acids is assembled into a protein (see Proteins section). In summary, the codes on DNA 

Nt = Typical nucleotide (phospate+sugar+base) O = Oeoxynbase sugar residue O = Phosphate unit 

Schematic diagram of deoxyribonucleic acid (DNA) showing the pairing of nitrogen bases (A-T C-G) between parts of two strands of DNA, the backbone of each strand being composed of alternately linked sugar and phosphate units. 

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Other, more general effects of insulin on cellular function include stimulation of cell growth (increase in DNA and protein synthesis), inhibition of apoptosis, and modulation of ion-channel activity. 

Elephantopus mollis is interesting because it elaborates a series of cytotoxic antitumor germacranolides including molephantinin and phantomolin, which are cytotoxic in vitro and in vivo against Ehrlich ascites carcinoma and Walker 256 carcinosarcoma in rodents (104,105). Molephantinin mitigates DNA and protein synthesis in Ehrlich ascites carcinoma cells and DNA synthesis. What is the activity of molephantinin on apoptosis (106)1... 

Indicators of microbial activity in soil represent measurements at the ecosystem level (e.g., processes regulating decomposition of organic residues and nutrient cycling, especially nitrogen, sulfur and phosphorus). Measurements at the community level include bacterial DNA and protein synthesis. Frequency of bacteriophages is a measurement at the population level. 

An inhibition of DNA and protein synthesis in glioma and neuroblastoma cells has been found at the same mercury concentration [ 145, 146], neurons being much more sensitive to mercuric chloride than nonneuronal cells [147]. 

White SJ, Jacobs RS (1983) Effect of stypoldione on cell-cycle progression, DNA and protein-synthesis, and cell-division in cultured sea urchin embryos. Mol Pharmacol 24 500-508... 

Treatment of Rat-2 fibroblasts with various cell-permeable ceramides resulted, as discussed above, in a rapid inhibition of phospholipid synthesis. An intriguing observation was that C2-ceramides inhibited PC biosynthesis without affecting the synthesis of PE via the CDP-ethanolamine route. C2-ceramide are well known inducers of apoptosis and inhibit DNA- and protein synthesis (Obeid et al, 1993 Jayadev et al, 1995). C2-ceramide induced apoptosis in the rat-2 fibroblasts (Houweling et al, unpublished data), suggesting that inhibition of PE biosynthesis is not a prerequisite for apoptosis. 

While ionophore-stimulated 5-LO product release from neutrophils is often used as an indication of 5-LO inhibition, one must interpret these results cautiously. For example, halothane, an inhalation anaesthetic which may cause membrane perturbation [26], and colchicine, a microtubule disrupter [27], both were active, but presumably not because of 5-LO inhibition. A23187 is assumed to stimulate 5-LO by raising the intracellular calcium level, but this agent causes many other effects which may or may not be related to 5-LO activation, including changes in membrane potential, protein phosphorylation, phospholipid turnover, cyclic nucleotide levels, and DNA and protein synthesis [28]. Also, the effects of some putative 5-LO inhibitors on product release from neutrophils has been shown to vary with the stimulant used [29]. 

Their antibacterial and mutagenic activity is closely related to the reduction of the 5-nitro group, which is common to all nitroimidazole drugs, and the subsequent formation of reactive metabolites that bind to bacterial DNA, inhibiting DNA and protein synthesis in the microorganisms. Metabolism of 5-nitroimidaz-oles in mammals usually leads to covalently bound residues with a persistent imidazole structure. 

In the present context, the data referring to daily variations in the ratio between energy and plastic metabolism are of special interest. It has been found that the processes of energy catabolism predominate in the daytime, while duplication and replication of DNA and protein synthesis dominate... 

Direct measurement of DNA and protein synthesis in experimental animals suggest that in zinc deficiency protein synthesis is adversely affected (, ). Our own data on human subjects in these experiments show that the total protein, total collagen, and RNA-DNA ratio Increased as a result of zinc supplementation. The activity of deoxythymidine kinase was not measurable during the zinc restriction phase but became 70% of normal level after supplementation with zinc for 3 months. Similar data have been published for experimental animals. Thus, our data show that deoxythymidine kinase in human subjects also is a zinc-dependent enzyme, and an adverse effect of zinc deficiency on this enzyme may be responsible for decreased protein synthesis. Our studies do not rule out an adverse effect of zinc deficiency on protein catabolism. Further studies are required to establish the effect of zinc restriction on protein catabolism. 

The effects of valtrate, dihydrovaltrate, and deoxido-dihydrovaltrate, valepotriates extracted from V. wallichii (DC.), on cultured rat hepatoma cells have been studied. Valtrate killed 50% of the cell population at a concentration of 5 pM, Deoxido-dihydrovaltrate and dihydrovaltae demonstrated this same toxicity at double the dose. Valtrate was also the most potent inhibitor of DNA and protein synthesis (39). These results suggest a mechanism by which valerian may cause hepatotoxicity. 

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