Protein synthesis chain elongation

Early mechanistic studies in the 1960s demonstrated that tylophorine alkaloids irreversibly inhibit DNA synthesis and affected protein synthesis al the elongation stage of the translation cycle [84]. In HeLa cells, tylophorine (1) reversibly inhibits RNA synthesis and irreversibly inhibits DNA synthesis, but a predominant effect is exerted on protein synthesis and elongation of peptide chains by preventing breakdown of polyribosomes and release of nascent peptides. Tylocrebrine (2) was shown to have equivalent activity to emetine on inhibition of protein synthesis in Entamoeba histolytica [85]. Tylophorine and tylocrebrine were also found to inhibit protein synthesis in Ehrlich ascites cells and... 

Energy requirements in protein synthesis are high. Four energy-rich phosphoric acid anhydride bonds are hydrolyzed for each amino acid residue. Amino acid activation uses up two energy-rich bonds per amino acid (ATP AMP + PP see p. 248), and two GTPs are consumed per elongation cycle. In addition, initiation and termination each require one GTP per chain. 

The translation of the mRNA into proteins is the final step in the biological flow of information (see Fig. 6.1). Similar to other macromolecular polymerizations, protein synthesis can be divided into initiation, chain elongation, and termination. Critical players in this process are the aminoacyl transfer RNAs (tRNAs). These molecules form the interface between the mRNA and the growing polypeptide. Activation of tRNA involves the addition of an amino acid to its acceptor stem, a reaction catalyzed by an aminoacyl-tRNA synthetase. Each aminoacyl-tRNA synthetase is highly specific for one amino acid and its corresponding tRNA molecule. The anticodon loop of each aminoacyl-tRNA interacts... 

The ribosome can carry two aminoacyl-tRNAs simultaneously. In the chain elongation stage, the growing polypeptide is carried on one of these tRNAs. The chain is transferred to the second tRNA, which adds its amino acid to the growing peptide, and displaces the first tRNA. The ribosome then moves one codon along the mRNA to allow the next to be read. Termination of protein synthesis involves the release of the completed polypeptide, expulsion of the last tRNA, and dissociation of the ribosome from the mRNA. This is signaled by specific termination codons (UAA, UAG, or UGA) in the mRNA and requires the participation of various release factors. 

Bujdak, J., Eder, A., Yongyai, Y., Faybikova, K., and Rode, B. M. (1995). Peptide chain elongation a possible role of montmorillonite in prebiotic synthesis of protein precursors. Orig. Life Evol. Biosph., 5,431 1. 

At one point or another during protein synthesis, several other proteins will be associated with the ribosome. These include factors that help in initiating the synthetic process, others that help in elongating the peptide chain, and yet others that play a role in terminating the synthesis of a peptide chain. Beyond this, there is also the mRNA to consider, as well as the aminoacylated tRNA molecules. Finally, since protein biosynthesis consumes energy, there is the hydrolysis of ATP and GTP to AMP and GDP, respectively, by the ribosome. 

The pathway of protein synthesis translates the three-letter alphabet of nucleotide sequences on mRNA into the twenty-letter alphabet of amino acids that constitute proteins. The mRNA is translated from its 5 -end to its 3 -end, producing a protein synthesized from its amino-terminal end to its carboxyl-terminal end. Prokaryotic mRNAs often have several coding regions, that is, they are polycistronic (see p. 420). Each coding region has its own initiation codon and produces a separate species of polypeptide. In contrast, each eukaryotic mRNA codes for only one polypeptide chain, that is, it is monocistronic. The process of translation is divided into three separate steps initiation, elongation, and termination. The polypeptide chains produced may be modified by posttranslational modification. Eukaryotic protein synthesis resembles that of prokaryotes in most details. [Note Individual differences are mentioned in the text.]... 

We considered the structure of the ribosome in some detail in the previous chapter without referring to those sites that are functionally important in protein synthesis. Here we can localize some of the functional sites on the two ribosomal subunits (fig. 29.6). The mRNA binds to the smaller ribosomal subunit. The peptidyl transferase is an integral part of the 50S subunit, and the elongation factor EF-G binds to the 50S subunit. The nascent polypeptide chain exits through a channel in the 50S subunit. Two functional sites occur on... 

Fatty acid synthase (FAS) carries out the chain elongation steps of fatty acid biosynthesis. FAS is a large multienzyme complex. In mammals, FAS contains two subunits, each containing multiple enzyme activities. In bacteria and plants, individual proteins, which associate into a large complex, catalyze the individual steps of the synthesis scheme. 

In perfused liver it also has effects on synthesis of most types of RNA and on amino acid uptake, and these may underlie much of the action on protein synthesis. For most effects on the liver there appears to be a delay of 15-60 min between the application of hormone and the first manifestation of the effect. Ribosomes from liver of hypophysectomized rats possess a lowered ability to carry out protein synthesis [86] and the defect can be reversed by administration of GH in vivo or in vitro. The effect may be at least partly on the rate of elongation of the growing polypeptide chain [85]. 

Protein Synthesis—Peptide Chain Elongation Jean Lucas-Lenard and Laszlo Beres... 

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