Chloramphenicol, protein synthesis inhibition

Chloramphenicol (Chloromycetin) interferes witii or inhibits protein synthesis, a process necessary for the growth and multiplication of microorganisms. This is a potentially dangerous drug (see below), and therefore its use is limited to serious infections when less potentially dangerous drugp are ineffective or contraindicated. 

What could be the signal for the induction of the cold shock proteins It has been observed that shifting E. coli cells from 37 to 5 °C results in an accumulation of 70S monosomes with a concomitant decrease in the number of polysomes [129]. Further, it has been shown that a cold shock response is induced when ribosomal function is inhibited, e.g. by cold-sensitive ribosomal mutations [121] or by certain antibiotics such as chloramphenicol [94]. These data indicate that the physiological signal for the induction of the cold shock response is inhibition of translation caused by the abrupt shift to lower temperature. Then, the cold shock proteins RbfA, CsdA and IF2 associate with the 70S ribosomes to convert the cold-sensitive nontranslatable ribosomes into cold-resistant translatable ribosomes. This in turn results in an increase in cellular protein synthesis and growth of the cells. 

Of the fonr possible optical isomers of chloramphenicol, only the o-threo form is active. This antibiotic selectively inhibits protein synthesis in bacterial ribosomes by binding to the 50S subunit in the region of the A site involving the 23 S rRNA. The normal binding of the aminoacyl-tRNA in the A site is affected by chloramphenicol in such a... 

Feedback inhibition of amino acid transporters by amino acids synthesized by the cells might be responsible for the well known fact that blocking protein synthesis by cycloheximide in Saccharomyces cerevisiae inhibits the uptake of most amino acids [56]. Indeed, under these conditions, endogenous amino acids continue to accumulate. This situation, which precludes studying amino acid transport in yeast in the presence of inhibitors of protein synthesis, is very different from that observed in bacteria, where amino acid uptake is commonly measured in the presence of chloramphenicol in order to isolate the uptake process from further metabolism of accumulated substances. In yeast, when nitrogen starvation rather than cycloheximide is used to block protein synthesis, this leads to very high uptake activity. This fact supports the feedback inhibition interpretation of the observed cycloheximide effect. 

To establish whether rifaximin, like the other members of the rifamycin family [36, 58], specifically inhibits bacterial RNA synthesis the effect of this antibiotic as well as that of rifampicin and chloramphenicol on RNA (via 3H-uridine incorporation), DNA (via 3H-thymidine incorporation) and protein (via 35S-methionine incorporation) synthesis was studied in growing cultures of Escherichia coli [59], While chloramphenicol reduced protein synthesis, both rifaximin and rifampicin inhibited RNA synthesis in a concentration-dependent fashion. In contrast, none of them affected 3H-thymidine incorporation into DNA. These data suggest that rifaximin, like rifampicin, inhibits RNA synthesis by binding the (3 subunit of the bacterial DNA-dependent RNA polymerase [60],... 

The answer is b. (Hardman, p 1131.) Chloramphenicol inhibits protein synthesis in bacteria and, to a lesser extent, in eukaryotic cells. The drug binds reversibly to the. 505 ribosomal subunit and prevents attachment of aminoacybtransfer RNA (tRNA) to its binding site. The amino acid substrate is unavailable for peptidyl transferase and peptide bond formation. 

Certain antibiotics (for example, chloramphenicol) inhibit mitochondrial protein synthesis, but not cytoplasmic protein synthesis, because mitochondrial ribosomes are similar to prokaryotic ribosomes. 

The use of antibiotics for the control of plant virus diseases( ) is of interest. Several antibiotics have been tested for inhibition of replication of viral nucleic acid and/or protein synthesis within the host cell. Chloramphenicol, cycloheximide, actinomycin D and others are the most used antibiotics and the disease caused by tobacco mosaic... 

Inhibition of protein synthesis in microorganisms (aminoglycosides, erythromycin, clindamycin, chloramphenicol, and tetracyclines). 

Pharmacology Chloramphenicol binds to 50 S ribosomal subunits of bacteria and interferes with or inhibits protein synthesis. 

Chloramphenicol is able to inhibit the peptidyl transferase reaction and so bacterial protein synthesis by binding reversibly to the 50s ribosomal subunit. Resistance can occur due to the plasmid-mediated enzyme chloramphenicol acetyltransferase which inactivates the drug by acetylation. Such resistance is often a part of plasmid-mediated multidrug resistance. Resistance can also occur by an altered bacterial permeability. However in most instances resistance to chloramphenicol only develops slowly and remains partial. 

Mostly chloramphenicol is well tolerated with only mild gastrointestinal disturbances. However this antibiotic inhibits mitochondrial protein synthesis in red blood cell precursors in the bone marrow and thus may cause dose-dependent anemia. This dose dependent reaction should not be confused with the idiosyncratic aplastic anemia which is dose-independent and usually fatal. The onset of this idiosyncrasy which has an incidence of about 1 20 000-1 50 000 may be during the treatment or weeks to months after therapy. 

Macrolides bind to the SOS ribosomal subunit of bacteria but not to the SOS mammalian ribosome this accounts for its selective toxicity. Binding to the ribosome occurs at a site near peptidyltransferase, with a resultant inhibition of translocation, peptide bond formation, and release of oligopeptidyl tRNA. However, unlike chloramphenicol, the macrolides do not inhibit protein synthesis by intact mitochondria, and this suggests that the mitochondrial membrane is not permeable to erythromycin. 

The lincosamide family of antibiotics includes lin-comycin (Lincocin) and clindamycin (Cleocin), both of which inhibit protein synthesis. They bind to the SOS ri-bosomal subunit at a binding site close to or overlapping the binding sites for chloramphenicol and erythromycin. They block peptide bond formation by interference at either the A or P site on the ribosome. Lincomycin is no longer available for human use in the United States. 

Inhibit protein synthesis impairment of Tetracyclines, chloramphenicol, aminoglycosides. 

Chloramphenicol inhibits hepatic microsomal enzymes that metabolize several drugs. Half-lives are prolonged, and the serum concentrations of phenytoin, tolbutamide, chlorpropamide, and warfarin are increased. Like other bacteriostatic inhibitors of microbial protein synthesis, chloramphenicol can antagonize bactericidal drugs such as penicillins or aminoglycosides. 

Tetracyclines inhibit protein synthesis in bacteria by blocking the A site on the ribosome, preventing the binding of aminoacyl-tRNAs. Chloramphenicol inhibits protein synthesis by bacterial (and mitochondrial... 

Mechanism of Action of Florfenicol. The inhibitory activities of chloramphenicol (1, R = NCh). thiamphenicol (1, R = SO2CH3), and florfenicol (2) against a sensitive E cofi strain have been studied. In two different liquid media, both chloramphenicol and florfenicol allowed only 20-30% residual growth at a drug concentration of 2 mg/L, whereas a thiaiuplieiiicul concentration of 25 mg/L was required to produce a similar effect. Florfenicol was also found to be a selective inhibitor of prokaryotic cells. At concentrations of 1 mg/L chloramphenicol and florfenicol, and at a concentration of 25 mg/L, thiamphenicol, inhibited protein synthesis. 

On the other hand, drugs may inhibit the metabolism of other drugs. For example, allopurinol (a xanthine oxidase inhibitor that inhibits the synthesis of uric acid) increases the effectiveness of anticoagulants by inhibiting their metabolism. Chloramphenicol (a potent inhibitor of microsomal protein synthesis) and cimetidine (an H2-receptor blocker used in acid-pepsin disease) have similar properties. In addition, drugs may compete with each other in metabolic reactions. In methyl alcohol (methanol) poisoning, ethyl alcohol may be given intravenously to avert methanol-induced blindness and minimize the severe acidosis. Ethyl alcohol competes with methyl alcohol for... 

Many antibiotics do not fall into a well-defined subclass. Isolated examples include chloramphenicol (A.38), clindamycin (A.39), and linezolid (A.40) (Figure A.ll). All inhibit bacterial protein synthesis. 

There are a number of sites within the sequence of protein synthesis where antibiotics can act. These include (1) inhibition of the attachment of mRNA to 30S ribosomes by aminoglycosides (2) inhibition of tRNA binding to 30S ribosomes by tetracyclines (3) inhibition of the attachment of mRNA to the 50S ribosome by chloramphenicol and (4) erythromycin inhibition of the translocation step by binding to 50S ribosomes, thus preventing newly synthesized peptidyl tRNA moving from the acceptor to the donor site. 

To stop the translation reaction and further stabilize the ribosomal complexes, cycloheximide can be added in the eukaryotic system (Gersuk et al., 1997). For the same purpose chloramphenicol, an antibiotic that inhibits bacterial protein synthesis by binding to the 23S ribosomal RNA in the peptidyl transferase center, can be used in the E. coli system (Mattheakis et al., 1994). However, chloramphenicol was found to have no influence on the efficiency of E. coli ribosome display (Hanes and Pluckthun, 1997). 

The macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome, thus inhibiting the translocation steps of protein synthesis. Generally considered to be bacteriostatic, they may be cidal at higher doses. The binding site is either identical to or in close proximity to that for lincomycin, clindamycin, and chloramphenicol. 

The drug binds to the bacterial 50S ribosomal subunit and inhibits protein synthesis at the peptidyl transferase reaction. Because of the similarity of mammalian mitochondrial ribosomes to those of bacteria, protein synthesis in these organelles may be inhibited at high circulating chloramphenicol levels, producing bone marrow toxicity. 

Chloramphenicol blocks translation in bacteria by inhibiting peptidyltransferase of the large ribosomal subunit. It does not interfere with peptidyltransferase in the large subunit of eukaryotic ribosomes. However, the mitochondrion of animal cells contains ribosomes that are similar to bacterial ribosomes, and chloramphenicol can block protein synthesis in this organelle. This could contribute to the side effects of this drug when used in the treatment of animals. 

Although chloramphenicol inhibits carotenoid synthesis, it also inactivates photo-chemically responsive membranes in which carotenoids are located, and hence previous conclusions that the enzymes involved in carotenoid biosynthesis are themselves synthesized in the cytoplasm are not strictly valid. However, the demonstration367 that dark-grown Euglena gracilis, which has carotenoids localized in the proplastids, can synthesize carotenoids in the presence of chloramphenicol indicates that such synthesis is not dependent on protein synthesis in the proplastid. 

Chloramphenicol and chlortetracycline were the first antibiotics recognized to be inhibitors of protein synthesis on the basis of findings that they inhibited induced enzyme syntheses in bacteria after induction had occurred and syntheses had been under way for considerable periods of time37. ... 

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