Protein synthesis and inhibition

Anabolic steroids have been promoted as a means to foster protein synthesis and inhibit catabolism. Possibilities for considerable weight gain have been implied. In practice however these effects are disappointing, certainly in relation to the toxicity of these agents. In HIV-infected patients the administration of anabolic steroids appeared to result in a small increase in both lean body mass and body weight. The androgenic properties that all anabolic steroids have in common stand in the way of their therapeutic use. 

Insuhn is a protein hormone produced by the (5-ceUs of the islets of Langerhans in the pancreas. Insulin was the first protein hormone to be sequenced, the first substance to be measured by radioimmunoassay (RIA), and the first compound produced by recombinant DNA technology for practical use. It is an anaboUc hormone that stimulates the uptake of glucose into fat and muscle, promotes the conversion of glucose to glycogen or fat for storage, inhibits glucose production by the liver, stimulates protein synthesis, and inhibits protein brealcdown. 

The key role of insuhn in protein metabolism usually is evident only in diabetic patients with persistently poor glycemic control. Insulin stimulates amino acid uptake and protein synthesis and inhibits protein degradation in muscle and other tissues. The increased conversion of amino acids to glucose also results in increased production and excretion of urea and ammonia. In addition, there are increased circulating concentrations of branched-chain amino acids as a result of increased proteolysis, decreased protein synthesis, and increased release of branched-chain amino acids from the liver. 

H. Others. The cytotoxic actions of other antineoplastic drugs result from a variety of mechanisms, including blockade of protein synthesis and inhibition of hormone release. 

Akt can also stimulate cell growth and proliferation by activating mTOR to increase protein synthesis and inhibiting GSK3p to increase p-catenin-induced transcription of proliferation genes. Cd " generally activates Akt signaling in various cell types, concentrations and exposure times [460,586,587], not only as a stress response, but as an adaptive reaction to prevent cell death. 

Potassium is required for enzyme activity in a few special cases, the most widely studied example of which is the enzyme pymvate kinase. In plants it is required for protein and starch synthesis. Potassium is also involved in water and nutrient transport within and into the plant, and has a role in photosynthesis. Although sodium and potassium are similar in their inorganic chemical behavior, these ions are different in their physiological activities. In fact, their functions are often mutually antagonistic. For example, increases both the respiration rate in muscle tissue and the rate of protein synthesis, whereas inhibits both processes (42). 

With the aid of cytosine permease, flucytosine reaches the fungal cell where it is converted by cytosine deaminase into 5-fluorouracil [51-21-8]. Cytosine deaminase is not present in the host, which explains the low toxicity of 5-FC. 5-Fluorouracil is then phosphorylated and incorporated into RNA and may also be converted into 5-fluorodeoxyuridine monophosphate, which is a potent and specific inhibitor of thymidylate synthetase. As a result, no more thymidine nucleotides are formed, which in turn leads to a disturbance of the DNA-synthesis. These effects produce an inhibition of the protein synthesis and cell repHcation (1,23,24). 5-Fluorouracil caimot be used as an antimycotic. It is poorly absorbed by the fungus to begin with and is also toxic for mammalian cells. 

The antiviral activity of (5)-DHPA in vivo was assessed in mice inoculated intranasaHy with vesicular stomatitis vims ( 5)-DHPA significantly increased survival from the infection. (5)-DHPA did not significantly reduce DNA, RNA, or protein synthesis and is not a substrate for adenosine deaminase of either bacterial or mammalian origin. However, (5)-DHPA strongly inhibits deamination of adenosine and ara-A by adenosine deaminase. Its mode of action may be inhibition of Vadenosyl-L-homocysteine hydrolase (61). Inhibition of SAH hydrolase results in the accumulation of SAH, which is a product inhibitor of Vadenosylmethionine-dependent methylation reactions. Such methylations are required for the maturation of vital mRNA, and hence inhibitors of SAH hydrolase may be expected to block vims repHcation by interference with viral mRNA methylation. 

Oxazolidinones are a new class of synthetic antimicrobial agents, which have activity against many important pathogens, including methicillin-resistant Staphylococcus aureus and others. Oxazolidinones (e.g. linezolid or eperezolid) inhibit bacterial protein synthesis by inhibiting the formation of the 70S initiation complex by binding to the 50S ribosomal subunit close to the interface with the 3OS subunit. 

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

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. 

Protein synthesis and selective inhibition 5.3 DHFR inhibitors... 

The macrolide erythromycin inhibits protein synthesis and resistance is induced by N -dimethyl-ation of adenine within the 23S rRNA, which results in reduced affinity of ribosomes for antibiotics related to erythromcin (Skinner et al. 1983). Sulfonamides function by binding tightly to chromosomal dihydropteroate synthetase and resistance to sulfonamides is developed in the resistance plasmid through a form of the enzyme that is resistant to the effect of sulfonamides. 

The reported (14) mechanisms of action of allelochemlcals Include effects on root ultrastructure and subsequent Inhibition of Ion absorption and water uptake, effects on hormone-induced growth, alteration of membrane permeability, changes In lipid and organic acid metabolism, inhibition of protein synthesis and alteration of enzyme activity, and effects on stomatal opening and on photosynthesis. Reduced leaf water potential Is one result of treatment with ferulic and p-coumaric acids (15). Colton and Einhellig (16) found that aqueous extracts of velvetleaf (Abutllon theophrastl Medic.) Increased diffusive resistance In soybean fGlycine max. (L.) Merr.] leaves, probably as a result of stomatal closure. In addition, there was evidence of water stress and reduced quantities of chlorophyll In Inhibited plants. 

Piddock, L. J. V., Walters, R. N., and Diver, J. M. (1990). Correlation ofquinolone MIC and inhibition ofDNA, RNA and protein synthesis and induction of the SOS response in Escherichia coli. Antimicrob. Agents Chemother. 34, 2331-2336. 

Rapid-acting dermally hazardous cytotoxin that inhibits protein synthesis and affects clotting factors in the blood. It is capable of producing incapacitating or lethal effects. T2 is obtained from various molds and fungi (Fusarium sp.). It is a colorless crystalline solid of white powder that melts at 304°F. Impure samples may be a colorless to slightly yellow oil. It is slightly soluble in water, but soluble in ethyl acetate, acetone, ethanol, chloroform, methylene chloride, diethyl ether, and dimethyl sulfoxide (DMSO). It is heat stable and can be stored at room temperature for years. 

Protein and RNA synthesis rates were significantly stimulated in liver, and inhibited in muscle in a dose-dependent manner. Maximum effect in both tissues occurred at 5 mg/L for protein synthesis and 0.2 mg/L for RNA synthesis... 

Marine algae transform arsenate into nonvolatile methylated arsenic compounds such as methanearsonic and dimethylarsinic acids (Tamaki and Frankenberger 1992). Freshwater algae and macrophytes, like marine algae, synthesize lipid-soluble arsenic compounds and do not produce volatile methylarsines. Terrestrial plants preferentially accumulate arsenate over arsenite by a factor of about 4. Phosphate inhibits arsenate uptake by plants, but not the reverse. The mode of toxicity of arsenate in plants is to partially block protein synthesis and interfere with protein phosphorylation — a process that is prevented by phosphate (Tamaki and Frankenberger 1992). 

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