336 / Biochemistry amino acid synthesis

Chio, K.S. and Tappel, A.L. (1969). Synthesis and characterisation of the fluorescent products derived from malonylalde-hyde and amino acids. Biochemistry 8, 2827-2832. 

Based on our current understanding of ribosomal protein synthesis, several strategies have been developed to incorporate amino acids other than the 20 standard proteinogenic amino acids into a peptide using the ribosomal machinery . This allows for the design of peptides with novel properties. On the one hand, such a system can be used to synthesize nonstandard peptides that are important pharmaceuticals. In nature, such peptides are produced by nonribosomal peptide synthetases, which operate in complex pathways. On the other hand, non-natural residues are a useful tool in biochemistry and biophysics to study proteins. For example, incorporation of non-natural residues by the ribosome allows for site-specific labeling of proteins with spin labels for electron paramagnetic resonance spectroscopy, with... 

It is important to appreciate that this principle of coupling-in-series underlies all biochemical pathways or processes, e.g. glycolysis, generation of ATP in the mitochondrion, protein synthesis from amino acids or a signal transduction pathway. Indeed, despite the fundamental importance of signalling pathways in biochemistry, a thermodynamic analysis of such a pathway has never been done, but the principles outlined above must apply even to signalling pathways. 

Translation involves three stages initiation, elongation and termination. A brief summary of these processes is provided below. However, the first step in polypeptide synthesis, from intracellular amino acids, is the formation of aminoacyl-tRNA. This reaction is particularly important so that the biochemistry is discussed in some detail. In addition, it is also important in the regulation of the rate of translation (see below). 

Lydon J, Duke SO, Inhibitots of glutamine synthesis, in Singh BK (ed.). Plant Amino Acids Biochemistry and Biotechnology, Marcel Dekket, New York, pp. 445— 464,1999. 

Pyridoxal phosphate is the coenzyme for the enzymic processes of transamination, racemization and decarboxylation of amino-acids, and for several other processes, such as the dehydration of serine and the synthesis of tryptophan that involve amino-acids (Braunstein, 1960). Pyridoxal itself is one of the three active forms of vitamin B6 (Rosenberg, 1945), and its biochemistry was established by 1939, in considerable part by the work of A. E. Braunstein and coworkers in Moscow (Braunstein and Kritzmann, 1947a,b,c Konikova et al 1947). Further, the requirement for the coenzyme by many of the enzymes of amino-acid metabolism had been confirmed by 1945. In addition, at that time, E. E. Snell demonstrated a model reaction (1) for transamination between pyridoxal [1] and glutamic acid, work which certainly carried with it the implication of mechanism (Snell, 1945). 

An understanding of protein synthesis, the most complex biosynthetic process, has been one of the greatest challenges in biochemistry. Eukaryotic protein synthesis involves more than 70 different ribosomal proteins 20 or more enzymes to activate the amino acid precursors a dozen or more auxiliary enzymes and other protein factors for the initiation, elongation, and termination of polypeptides perhaps 100 additional enzymes for the final processing of different proteins and 40 or more kinds of transfer and ribosomal RNAs. Overall, almost 300 different macromolecules cooperate to synthesize polypeptides. Many of these macromolecules are organized into the complex three-dimensional structure of the ribosome. 

Biochemically, folacin functions in vivo as coenzymes and carriers of one-carbon units for a number of enzyme reactions, including synthesis of amino acids, proteins, and nucleic acids (58,120,122). Folacin participates in both anabolic and catabolic reactions, and its metabolism is cyclic in nature. Greater detail on the biochemistry of folacin is available (120,122). 

My second comment is apropos of Channing Robertson s remarks, which I admired. In regard to polymers, it seems to me that the time has come to adopt again a unifying approach like that of Charles Tanford, professor of biochemistry at Duke University, who wrote the book Physical Chemistry of Macromolecules comparing biopolymers with synthetic polymers. In polymer synthesis, let s look at the synthesis of peptides, amino acid by amino acid, and the desynthesis of peptides by sequencing, and bring this into our curriculum. 

While chemical synthesis is mostly an art, with specialized reactions for both inorganic and inorganic synthesis, the complexities of biochemistry have nurtured specialized instruments that can split or assemble biomolecules. An automated solid-phase peptide synthesizer was introduced by Merrifield15 in 1963 this allows for the facile synthesis of oligopeptides (up to 100 amino acid units) [2], The enzyme DNA polymerase I was discovered by Komberg16 in 1957 this allowed the assembly of DNA from fragments [3]. 

This is a crude simplification of a beautiful process and you should turn to a biochemistry textbook for more details. The actual building up of a strand of DNA obviously Involves a complex series of chemical reactions. The DNA Is then used to build up a complementary strand of RNA, which does have the 2 hydroxyl group, and the RNA then Instructs the cell on protein synthesis using three-nucleotide codes to Indicate different amino acids. Again, the details of this process are beyond the scope of this book, but the code Is not. 

Ugi, i., Marquarding, D., Urban, R. Synthesis of peptides by four-component condensation, in Chemistry and Biochemistry of Amino Acids, Peptides, and Proteins 6, 245-289 (1982). 

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