RNA biosynthesis

To supply reducing equivalents for biosynthesis (NADPH) and pentoses for DNA and RNA biosynthesis. 

El-Sebae, A.H., M.H. Salem, M.R.S. El-Assar, and E.E. Enan. 1988. In vitro effect of profenofos, fenvalerate and dimilin on protein and RNA biosynthesis by rabbit liver and muscle tissues. Jour. Environ. Sci. Health B23 439-451. 

These three compounds exert many similar effects in nucleotide metabolism of chicks and rats [167]. They cause an increase of the liver RNA content and of the nucleotide content of the acid-soluble fraction in chicks [168], as well as an increase in rate of turnover of these polynucleotide structures [169,170]. Further experiments in chicks indicate that orotic acid, vitamin B12 and methionine exert a certain action on the activity of liver deoxyribonuclease, but have no effect on ribonuclease. Their effect is believed to be on the biosynthetic process rather than on catabolism [171]. Both orotic acid and vitamin Bu increase the levels of dihydrofolate reductase (EC 1.5.1.4), formyltetrahydrofolate synthetase and serine hydroxymethyl transferase in the chicken liver when added in diet. It is believed that orotic acid may act directly on the enzymes involved in the synthesis and interconversion of one-carbon folic acid derivatives [172]. The protein incorporation of serine, but not of leucine or methionine, is increased in the presence of either orotic acid or vitamin B12 [173]. In addition, these two compounds also exert a similar effect on the increased formate incorporation into the RNA of liver cell fractions in chicks [174—176]. It is therefore postulated that there may be a common role of orotic acid and vitamin Bj2 at the level of the transcription process in m-RNA biosynthesis [174—176]. 

As with many enzymes the role of AMP aminohydrolase in the hierarchy of metabolic catalysts is not clearly understood. Enzymic activity in muscle is markedly reduced in the dystrophic mouse (161, 162), in humans suffering from Duchanne type muscular dystrophy (163), in hypokaliemic periodic paralysis (164), and upon denervation of normal and dystrophic mouse gastronemii (165). Activity is reported to increase in both transplanted and primary hepatomas (151) and in precancerous livers prior to the onset of neoplasia induced by feeding or by intraabdominal injections of the potent carcinogen 3 -methyl-4-dimethyl-aminoazobenzene (166). The weak carcinogen, 4 -methyl-4-dimethyl-aminoazobenzene was not effective (166). Increases in enzyme activity concomitant with altered nuclear-nucleolar morphology, nuclear RNA content, and nuclear RNA biosynthesis were also observed after injections of thioacetamide, a hepatocarcinogen (167, 168). 

Cells are able to synthesize genetic material (DNA, RNA) from endogenous metabolites known as purine and pyrimidine nucleotides (Fig. 36-3). Certain anticancer drugs are structurally similar to these endogenous metabolites and compete with these compounds during DNA/RNA biosynthesis. These drugs are therefore called antimetabolites because they interfere with the normal metabolites during cellular biosynthesis.16,80... 

Miyach and co-workers (Miyachi, 1962 Miyachi and Miyachi, 1961 Miyachi and Tamiya, 1961 Miyachi et al, 1964) have shown that utilization of different PolyP fractions for nucleic acid biosynthesis in Chlorella is different in the light and in the dark. In the opinion of these authors, PolyPs of different fractions are involved in the biosynthesis of nucleic acids and other compounds in different ways. In the light, fraction C is a phosphorus donor for the biosynthesis of chloroplast DNA, while fraction A is involved in the synthesis of nuclear DNA. RNA is not formed in this alga from PolyP under conditions of Pi sufficiency, although PolyPs of fractions B and D are utilized for RNA biosynthesis when Pj is absent in the medium. In the light, the PolyPs of these fractions are hydrolysed to Pi, which is then utilized for the biosynthesis of RNA and other compounds. In the dark and in the absence of Pj, PolyP seems to be able to provide phosphate for RNA synthesis. 

Inhibition of RNA Synthesis usually has bacteriostatic consequences since it does not result in severely unbalanced biosynthesis and growth. When RNA biosynthesis is turned off by an inhibitor, the cell cannot replenish messenger RNA which, in microorganisms, is subject to rapid turnover. The progressive deficiency in messenger RNA results in a progressive decay in the rate of protein biosynthesis. 

One example of an enzyme-catalyzed reaction involving a radical intermediate is the enzyme ribonucleotide reductase, which catalyzes the conversion of ribonucleotides (used for RNA biosynthesis) to 2 -deoxyribonucleotides (used for DNA biosynthesis), as illustrated in Fig. 16. Spectroscopic studies of the R2 subunit of Escherichia coli ribonucleotide reductase have shown that it can form a stable, long-lived, tyrosyl radical species—the first protein radical to be discovered (13). 

Holotoxin Ai inhibits the RNA biosynthesis in Candida albicans and Saccharomyces carlsbergensis, as indicated by the decrease in incorporation of C-uridine to the acid-insoluble fraction of the cells. Similar results were obtained for glycoside fractions of 14 species of Pacific sea cucumbers [132]. Apparently the inhibition of RNA biosynthesis in Saccharomyces carlsbergensis is related to nucleotide loss from yeast cells after treatment with glycosides. Holotoxin Ai also inhibits biosyntheses of squalene, lanosterol and ergosterol in S. carlsbergensis [133]. Mitosis is arrested and DNA synthesis inhibited in onion root bulbs by crude holothurin [134]. 

Nucleic acid metabolism is dominated by phosphoryl transfer reactions (Figure 10.13). These include the reactions involved in DNA and RNA biosynthesis, catalysed by DNA and RNA polymerases. In these reactions. 

Tri phosph ate, C, 0H, 3 N sO, 2 P3, cordycepi ii 5 triph osphate 3 deoxy ATP. 3 deoxyadeltosine 5, dtetrahydrogen triphosphate) Inhibits the final step of RNA biosynthesis by termination of the ribonucleotide chain due to the absence of the 3 -hydroxyl group. Formation by conversion of 3 -de-oxyadeno ine in Ehrlich ascites tumor H. Klenow, Biochim. Biophys, Acta 76, 347 (1963), Metabolism in K.B cells H, Shigeura, S. Sampson, ibid, 138, 26 (1967). Synthesis J, J, Novak, F. Sorm. Coll Czech. Chem. Common, 38, 113 (1973) M, Blandin. / Carbahyd. Nuch, Nucl 3(5/6), 341 (1976). 

Pyrimidines play a central role in cellular regulation and metabolism. They are substrates for DNA and RNA biosynthesis, regulators of biosynthesis of some amino acids, and cofactors in the biosynthesis of phospholipids, glycolipids, sugars, and polysaccharides (17B45). Pyrimidine biosynthesis is very complicated and involves formic acid, glutamate, and aspartate as starting materials in a series of enzymatic reactions to eventually form orotic acid. Orotic acid, or uracil-... 

Flucytosine is a powerful antifungal agent used in the treatment of serious systemic fungal infections, such as Cryptococcus neoformans and Candida spp (Table 40.2). Flucytosine itself is not cytotoxic but, rather, is a pro-drug that is taken up by fungi and metabolized to 5-fluorouracil (5-FU) by fungal cytidine deaminase (Fig. 40.11) (51). Then, 5-FU is converted to 5-fluorodeoxyuridine, which as a thymidylate synthase inhibitor interferes with both protein and RNA biosynthesis. 5-Fluorouracil is cytotoxic and is employed in cancer chemotherapy (see Chapter 42). Human cells do not contain cytosine deaminase and, therefore, do not convert flucytosine to 5-FU. Some intestinal flora, however, do convert the drug to 5-FU, so human toxicity does result from this metabolism. Resistance rapidly develops to flucytosine when used alone, so it is almost always used in conjunction with amphotericin B. Use of flucytosine has declined since the discovery of fluconazole. 

Polarity of DNA synthesis DNA polymerase adds nucleotide units to 3 -OH of the pre-existing chain. Thus DNA biosynthesis (likewise RNA biosynthesis) proceeds in one chemical direction, from the 5 to the 3 end. This directionality has given rise to the convention that polynucleotide sequences are read from left to right in the 5 3 direction. 

CioHijNjO, Mr 251.24, needles, mp. 225 -226°C, [oId -47° (H2O), well soluble in water. Metabolite from culture broths of Cordyceps, Isaria, Emericella, and Aspergillus species. C. exhibits strong cytotoxic activity by inhibition of RNA biosynthesis. Because of this property C. is used for investigations on messen-ger-RNA transcription. C. was the first nucleoside antibiotic to be described (1951) and was isolated from Cordyceps militaris. C. selectively inhibits the poly-adenylation of hnRNA in HeLa cells at 50 pg/mL. Furthermore not only 45S-rRNA biosynthesis but also adenylate cyclase are inhibited. 

Activity The R. have tumorstatic activities as inter-calators, they inhibit DNA and RNA polymerase and to-poisomerase II and thus DNA and RNA biosynthesis. As a result of their binding to DNA the R. are toxic. 

Folate (Bp) Lc. lactis. Strep. DNA and RNA biosynthesis amino acid [87-104]... 

Folates Folates are foUc acid derivatives that are naturally present in foods. FoUc acid is the chemically synthesized form of folate. Folates are involved in many metaboUc pathways such as DNA and RNA biosynthesis, repair and methylation, and amino acid interconversions. These compounds possess antioxidant competence that protects the genome by preventing free radical attack [238]. In humans, folate deficiency is associated with a variety of disorders such as coronary heart disease, osteoporosis, Alzheimer s disease, and increased risk of breast and colorectal cancer [239]. 

RNA biosynthesis is similar to DNA synthesis but includes one extra step, which is transcription of DNA into RNA molecule by RNA polymerase enzyme. For replication of natural RNA of interest, a reverse transcription is... 

Experiments with inhibitors of proteins or RNA biosynthesis indicate that the stimulating action of RF s on the release of gonadotropins, even if it is slightly diminished during the incubation with puromycin and... 

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