Biosynthesis of proteins

Biosynthesis of Protein. The dynamic equilibrium of body protein was confirmed by animal experiments using A/-labeled amino acids in 1939 (104). The human body is maintained by a continuous equilibrium between the biosynthesis of proteins and their degradative metabolism where the nitrogen lost as urea (about 85% of total excreted nitrogen) and other nitrogen compounds is about 12 g/d under ordinary conditions. The details of protein biosynthesis in living cells have been described (2,6) (see also Proteins). 

Much of protein engineering concerns attempts to explore the relationship between protein stmcture and function. Proteins are polymers of amino acids (qv), which have general stmcture +H3N—CHR—COO , where R, the amino acid side chain, determines the unique identity and hence the stmcture and reactivity of the amino acid (Fig. 1, Table 1). Formation of a polypeptide or protein from the constituent amino acids involves the condensation of the amino-nitrogen of one residue to the carboxylate-carbon of another residue to form an amide, also called peptide, bond and water. The linear order in which amino acids are linked in the protein is called the primary stmcture of the protein or, more commonly, the amino acid sequence. Only 20 amino acid stmctures are used commonly in the cellular biosynthesis of proteins (qv). 

Ribosomal RNAs characteristically contain a number of specially modified nucleotides, including pseudouridine residues, ribothymidylic acid, and methylated bases (Figure 11.26). The central role of ribosomes in the biosynthesis of proteins is treated in detail in Chapter 33. Here we briefly note the significant point that genetic information in the nucleotide sequence of an mRNA is translated into the amino acid sequence of a polypeptide chain by ribosomes. 

The repertoire of a-amino acids used by nature in the biosynthesis of proteins is limited to about 20 structures. Since the diversity of synthetically accessible a-amino acids is enormous, initial studies have been undertaken to investigate the possibilities offered by incorporation of noncoded amino acids into en2ymes. Some selected examples of successful modifications are presented below. 

The ATP molecule is a universal energy carrier in the cell, and it is the principal one. It will sustain all reactions and processes requiring Gibbs energy active ion transport (ion pump operation), biosynthesis of proteins and other substances, muscle contraction, and so on. It is also employed for temporary energy storage in the cell. 

The diet must provide those amino acids which the body cannot synthesize (essential amino acids, EAA) and nitrogen in the form of nonessential amino acids (NEA). Both EAA and NEA are required for biosynthesis of proteins and other nitrogen-containing compounds necessary for homeostasis or growth. Thus, the total nitrogen content of a specific food must be considered to be nutritionally significant. 

It is interesting to note that serine peptidases can, under special conditions in vitro, catalyze the reverse reaction, namely the formation of a peptide bond (Fig. 3.4). The overall mechanism of peptide-bond synthesis by peptidases is represented by the reverse sequence f-a in Fig. 3.3. The nucleophilic amino group of an amino acid residue competes with H20 and reacts with the acyl-enzyme intermediate to form a new peptide bond (Steps d-c in Fig. 3.3). This mechanism is not relevant to the in vivo biosynthesis of proteins but has proved useful for preparative peptide synthesis in vitro [17]. An interesting application of the peptidase-catalyzed peptide synthesis is the enzymatic conversion of porcine insulin to human insulin [18][19]. 

In protein synthesis, there are three classes of RNA to worry about ribosomal RNA, rRNA messenger RNA, mRNA and transfer RNA, tRNA. All three classes of RNA play key roles in the final stage of the process the biosynthesis of proteins. However, we are going to take this one step at a time. We turn attention first to the... 

To understand what is going on in the biosynthesis of proteins, we need to keep in mind what we are trying to achieve. Here is how the logic goes. 

Borsook s review article (1952) is a good starting point for a consideration of changes in thought which have occurred with regard to biosynthesis of protein. .. the possibility that synthesis could occur by reverse of hydrolysis of proteins. .. is discussed (and disagreed with) and so is protein synthesis by transpeptidation. Both theories were current at the time. .. Borsook needs only half a page to discuss the role of nucleic units in protein synthesis. 

A wide variety of other biochemical effects has been reported to be associated with treatment of cells with vinblastine, vincristine, and related compounds (S). These effects include inhibition of the biosynthesis of proteins and nucleic acids and of aspects of lipid metabolism it is not clear whether such effects contribute to the therapeutic or toxic actions of vincristine and vinblastine. Vinblastine and vincristine inhibit protein kinase C, an enzyme system that modulates cell growth and differentiation (9). The pharmacological significance of such inhibition has not been established, however, and it must be emphasized that the concentrations of the drugs required to inhibit protein kinase C are several orders of magnitude higher than those required to alter tubulin polymerization phenomena (10). 

Numerous publications on uracil and thymine and their role in controlling the metabolism, reproduction, and growth of living systems — in particular in the transcription of genetic information and biosynthesis of proteins — have already appeared in the literature. Therefore, these two important pyrimidines will not be discussed again in the present review. Some pertinent literature references are provided [244—264]. 

H. Chantrenne, The Biosynthesis of Proteins, Pergamon Press, London, 1961... 

A similar approach is employed in the formation of peptides such as peptide antibiotics (see Box 13.11). In marked contrast to the ribosomal biosynthesis of proteins, where a biological production line interprets the genetic... 

Enzymic transfer of D-xylose from uridine 5 -(D-xylopyranosyI-HC pyrophosphate) to L-serine residues of endogenous protein acceptors from (a) a cell tumor of the mouse188 and (b) chick-embryo cartilage189 occurs in cell-free extracts of both of these tissues, in the absence of biosynthesis of protein. The enzyme preparations employed were from the supernatant liquor, although activity was also present in the insoluble fractions. In these two types of tissue, the acceptors are heparin and chondroitin sulfate, respectively, but the presence of other D-xylose-containing glycoproteins in ascites fluid from... 

ER content overall is larger both on the smooth and rough sides. Recall that the rough endoplasmic reticulum is responsible for the biosynthesis of protein. The substances which cause induction can therefore affect the rate of their own metabolism or the rate of biotransformation of some other substance or both. The following are some examples of substances which can cause induction and the metabolisms which they induce. 

Group Y may be - OR (esters), - SR (thioesters) or - NHR (amides or peptides). If B is a hydroxyl ion formed from H20, the reaction is hydrolysis. If B is the anion of an alcohol, thiol, or amine, the reaction is transacylation. Transacylation is an essential process in biosynthesis of proteins and lipids, but it is the digestive enzymes, which catalyze hydrolysis, that have been studied most intensively. 

Schachtschabel, D. and Zillig, W. (1959) Investigations on the biosynthesis of proteins. I. Synthesis of radiocarbon labeled amino acids in proteins of cell-free nucleoprotein-enzyme-system of Escherichia coli. Hoppe-Seyler s Z. Physiol. Chem. 314, 262-275. 

Ribosomes are spherical cell structures enriched with ribonucleoprotein and with a diameter of 15-20 nm. Each ribosome is formed by two subunits of different sizes, only visible through high resolution electron microscopy. Ribosomes connected to the rough endoplasmic reticulum are involved in the biosynthesis of proteins that are temporarily stored or transported to the cell s outer environment. Proteins synthesized by ribosomes connected to membranes accumulate in the cisternae before passage to the plasma membrane for secretion. 

The biosynthesis of proteins is the subject of biochemistry and will not be covered here. In the laboratory, if we were to heat a mixture of oc-amino acids together in an attempt to form a polypeptide, the result would be only a random copolymer. To synthesize a peptide or protein, we would have to... 

The reactions of phase 1 are the well established processes of template-directed biosynthesis of protein involving the various types of deoxyribonucleic and ribonucleic acids, the chain-initiating and the chain-terminating factors, and the appropriate enzymes for activating the amino acids and assembling them into a polypeptide chain. These processes are multi-type reactions proceeding in an integrated and coordinated manner. The reactions of this phase are excellently presented in a review.100... 

Schwartz B and Klinman JP (2001) Mechanisms of biosynthesis of protein-derived redox cofactors. Vitamins and Hormones B, 219-39. 

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