Synthesis continued proteins

After this initial phase of infection subsides, the free viral load in the blood declines, often to almost undetectable levels. This latent phase may last for anything up to 10 years or more. During this phase, however, there does seem to be continuous synthesis and destruction of viral particles. This is accompanied by a high turnover rate of (CD4+) T-helper lymphocytes. The levels of these T-lymphocytes decline with time, as does antibody levels specific for viral proteins. The circulating viral load often increases as a result, and the depletion of T-helper cells compromises general immune function. As the immune system fails, classical symptoms of AIDS-related complex (ARC) and, finally, full-blown AIDS begin to develop. 

The plasma membrane of the cell is a lipid bilayer sheet in which membrane-bound proteins are embedded. Steps 4B-6B of Figure 1.21 illustrate some events in the production of a membrane-bound protein. After synthesis of the protein, the ribosome on which it was formed dissociates from the membrane but the protein remains bound to the membrane (Step 4B). This binding is mediated by a short stretch of lipophilic amino acids that may occur near the C terminus, as shown in Figure 1.21, or near the N terminus in the case of other proteins. Subsequently, part of the ER membrane forms a bud that breaks off (Step 5B) to form a secretory vesicle (Step 6B). The continued association of the entire membrane-bound protein during the budding process and during subsequent events is maintained by the special lipophilic sequence. Eventually, the secretory vesicle fuses with the plasma membrane in a process that resembles a reversal of Steps 4B-6B. After completion of the insertion of the membrane-bound protein into the plasma membrane, its N terminus is in contact with the extracellular fluid and its C terminus is in contact with the cytoplasm, at least for the protein depicted in Figure 1.21. 

Plasma lipoproteins are in a dynamic state. Their continuous synthesis and degradation are accompanied by rapid exchanges of lipid and protein components between... 

An important aspect of mRNA regulation is determined by the turnover of mRNA molecules, i.e., translation can occur only as long as the mRNA remains intact. In bacteria, mRNA molecules have a lifetime of only a few minutes, and continued synthesis of mRNA molecules is needed to maintain synthesis of the proteins encoded in the mRNAs. In eukaryotes, the lifetime of mRNA is generally quite long (hours or days), thereby enabling a small number of transcription initiation events to produce proteins over a long period of time. 

Mach, Reich and Tatum were able to demonstrate an inhibition of the biosynthesis of protein in cells of B. brevis by chloramphenicol and puromycin without affecting the synthesis of tyrocidine . Several analogues of amino acids were found, which inhibited the biosynthesis of tyrocidine without affecting that of protein and vice versa. In contrast to protein synthesis, the production of tyrocidine did not depend on the continuous synthesis of RNA. Furthermore, environmental factors were able to control the relative amounts of the different tyrocidines synthesized by genetically homogeneous cultures . Addition of phenylalanine to the culture medium resulted in the almost exclusive synthesis of tyrocidine A, whereas the unsupplemented culture produced tyrocidine A, B and C. In the presence of tryptophan, a new form of tyrocidine, called tyrocidine D, containing three tryptophan in place of three phenylalanine residues, was produced. This lack of absolute requirement for specific amino acids in the formation of a peptide bond is in contrast to the strict specificity of sequential incorporation of amino acids... 

Fig. 15.13. Synthesis of proteins on the RER. 1. Translation of the protein begins in the cytosol. 2. As the signal peptide emerges from the ribosome, a signal recognition particle (SRP) binds to it and to the ribosome and inhibits further synthesis of the protein. 3. The SRP binds to the SRP receptor in the RER membrane, docking the ribosome on the RER. 4. The SRP is released and protein s5mthesis resumes. 5. As the signal peptide moves through a pore into the RER, a signal peptidase removes the signal peptide. 6. Synthesis of the nascent protein continues, and the completed protein is released into the lumen of the RER.

Murakami Y, Yoshida T, Hayashi S et al. (2000) Continuous enzymatic production of peptide precursor in aqueous/organic biphasic medium. Biotechnol Bioeng 69 57-65 Nakanishi K, Takeuchi A, Matsuno R (1990) Long term continuous synthesis of aspartame precursor in a column reactor with an immobilized thermolysin. Appl Microbiol Biot 32 633-636 Nardin EH, Calvo-CaUe JM, Oliveira GA et al. (1998). Plasmodium falciparum polyoximes highly immunogenic synthetic vaccines constructed by chemoselective ligation of repeat B-ceU epitopes and a universal T-ceU epitope of CS protein. Vaccine 16 590-600 Nilsson B, SoeUner M, Raines R (2005) Chemical synthesis of proteins. Annu Rev Biophys Biomol Struct 34 91-118... 

Thus, cell enlargement, for instance, depends upon auxin and involves the uptake of water, extension of the cell membrane and protein synthesis. The auxin dose-response curve consists of two peirts promotion by low concentrations and inhibition by higher concentrations via the formation of ethylene. Cytokinins and abscisic acid may possibly induce also, under special conditions, the production of ethylene. Many publications deal with effects of these plant hormones, especially of auxin, on ethylene biosynthesis in plants which occurs after a lag phase of 30 - 60 minutes and is specifically blocked by rhizobitoxin as well as by inhibitors of ENA and protein synthesis indicating that a continuous synthesis of protein is required for high rate of ethylene production (Eef. 20). 

More recent work from Gross laboratory claims that at least some maternal mRNA s code for microtubule proteins, or, more correctly, for soluble proteins which, after partial purification by vinblastine precipitation, co-migrate on acrylamide gel electrophoresis with known microtubule proteins from sperm tails (Raff et ah, 1971, 1972). Although there is a pool of these microtubule proteins in the unfertilized egg it seems that this pool is maintained or supplemented (for the construction of such things as mitotic spindles and cilia) by continuous synthesis of the monomeric subunits from stored mRNA, starting from the first cleavage cycle. Hopefully, more detailed analysis of the relative rate of microtubule synthesis at different times after fertilization, in the absence of new RNA synthesis, will provide information about the way in which this particular maternal mRNA is utilized during development. 

In conclusion, on the basis of in vivo experiments, it was demonstrated that proteins undergo continuous synthesis and breakdown, and that their rate of synthesis is very rapid, although this varies depending upon the specific tissue and protein studied. 

A number of features distinguish the biosynthesis of outer membrane and periplasmic proteins from the cytoplasmic proteins. Examination of the sensitivity of cytoplasmic and outer membrane polypeptide synthesis to inhibitors of ribosome function suggests that the outer membrane proteins utilise different biosynthetic machinery. The biosynthesis of envelope proteins is strikingly more resistant to puromycin and kasugomycin than the transcription of cytoplasmic protein. In contrast, the synthesis of cytoplasmic proteins continues at levels of tetracycline and sparsomycin that... 

Some investigators(also T. G. Mitchell, personal communication) have reported a simplification of this liquid assay procedure in which the enumeration of viable cells is replaced by the determination of the turbidity of (undiluted) treated and control cultures. Although this modification is less expensive and more rapid—results are read immediately as opposed to the requirement for overnight incubation—we have some reservations about this modification, since it is known that DNA-inhibiting agents have a propensity for unbalanced growth, i.e., a continued synthesis of RNA and proteins in the absence of DNA synthesis, which is characterized by an increase in the... 

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