The Genetic Code and Protein Biosynthesis

It is beyond the scope of this book to give a detailed account of the genetic code, how it was unraveled, and how more than a hundred types of macromolecules must interact to translate that code into the synthesis of a protein. But we can present a few of the main concepts. 

The genetic code is the relationship between the base sequence in DNA, or its RNA transcript, and the amino acid sequence in a protein. A three-base sequence, called a codon, corresponds to one amino acid. Because there are 4 bases in RNA (A, G, C, and U), there are 4 X 4 X 4 = 64 possible codons. However, there are only 20 common amino acids in proteins. Each codon corresponds to only one amino acid, but the code is degenerate that is, several different codons may correspond to the same amino acid. Of the 64 codons, 3 are codes for stop (UAA, UAG, and UGA) they signal that the particular protein synthesis is complete. One codon, AUG, serves double duty. It is the initiator codon, but if it appears again after a chain has been initiated, it codes for the amino acid methionine. The entire code is summarized in Table 18.2. 

How was the genetic code solved The first successful experiment was performed by Marshall Nirenberg in 1961 (Nobel Prize, 1968). Nirenberg added a synthetic RNA, polyuridine (an RNA in which all of the bases were uracil, U), to a 

The genetic code is the relationship between the base sequence in DNA and the amino acid sequence in a protein. A three-base sequence located on mRNA, called a codon, corresponds to one amino acid. 

First base (5 end) Middie base Third base (3 end)  

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The Genetic Code and Protein Biosynthesis A WORD ABOUT... 

As described above, DNA determines the structure of mRNA. The mRNA has 64 possible triplet codons. However, there are only 20 amino acids. The code is actually highly degenerate most amino acid residues are designated by more than one triplet. Only Trp and Met are designated by single codons. Table 14.7 (95) provides the genetic code of protein biosynthesis. Note that three combinations indicate a termination of the translation and the carboxyl end of the protein chain. 

Nucleic acids Polymers made of phosphate-linked sugars bearing the heterocyclic bases adenine (A), guanine (G), cytosine (C), and thymine (T) in DNA or uracil (U) in RNA contain the genetic code for protein biosynthesis... 

Although L-phenylalanine is a protein amino acid, and is known as a protein acid type of alkaloid precursor, its real role in biosynthesis (providing C and N atoms) only relates to carbon atoms. L-phenylalanine is a part of magic 20 (a term deployed by Crick in his discussion of the genetic code) and just for this reason should also be listed as a protein amino acid type of alkaloid precursor, although its duty in alkaloid synthesis is not the same as other protein amino acids. However, in relation to magic 20 it is necessary to observe that only part of these amino acids are well-known alkaloid precursors. They are formed from only two amino acid families Histidine and Aromatic and the Aspartate family . 

The intensive studies on the genetic code and on the proteins in recent years have led to a fairly good understanding of the mechanism of protein biosynthesis . The biosynthetic mechanism involved in the formation of peptides has not yet been studied in equal detail. Some physiologically active peptides like bradykinin and angiotensin are known to be derived from proteins by a specific enzymatic hydrolysis. Other peptides, like glutathione - , ophthalmic acid , the nucleotide-pentapeptide from Staph, aureus and y-polyglutamic acid have been shown to require for their synthesis only a soluble enzyme system. Their biosynthetic mechanism is therefore entirely different from that of the proteins. Such a different type of mechanism has also been demonstrated lately to be involved in the synthesis of peptide antibiotics. 

Nucleic ocid DNA or RNA. the nucleotide polymers that carry the genetic code and govern protein biosynthesis. 

Section 26.11 Three RNAs are involved in gene expression. In the transcription phase, a strand of messenger RNA (mRNA) is synthesized from a DNA template. The four bases A, G, C, and U, taken three at a time, generate 64 possible combinations called codons. These 64 codons comprise the genetic code and code for the 20 amino acids found in proteins plus start and stop signals. The mRNA sequence is translated into a prescribed protein sequence at the ribosomes. There, small polynucleotides called transfer RNA (tRNA), each of which contains an anticodon complementary to an mRNA codon, carries the correct amino acid for incorporation into the growing protein. Ribosomal RNA (rRNA) is the main constituent of ribosomes and appears to catalyze protein biosynthesis. 

Coenzymes such as NAD, NADP and coenzyme A are concentrated in the aqueous phase of the matrix. The matrix also contains the protein synthesizing system of the M. Vertebrate M. contain Ribosomes (see) of size 50-55S, whereas the M. of other eukaryotic organisms contain 70S ribosomes. The DNA of M. is circular, histone-free, and attains a length (in mammals) of 5 pm. It contains cistrons for ribosomal RNA and tRNA, and the genes for ATPases, for 2 of the 3 subunits of cytochrome 6, and for 4 of the 7 subunits of cytochrome oxidase. The biosynthesis of all the other mitochondrial constituents appears to be under the genetic control of the cell nucleus. The genetic code and tRNA complement of M. are different from those of the cytoplasm (see Genetic code). 

Once the broad outlines of DNA replication and protein biosynthesis were established scien tists speculated about how these outlines af fected various origins of life scenarios A key question concerned the fact that proteins are re quired for the synthesis of DNA yet the synthesis of these proteins is coded for by DNA Which came first DNA or proteins How could DNA store genetic infor mation if there were no enzymes to catalyze the polymerization of its nucleotide components How could there be proteins if there were no DNA to code for them ... 

In marked contrast to the ribosomal biosynthesis of peptides and proteins where a biological production line interprets the genetic code of mRNA, many natural peptides are known to be synthesized by a... 

Fig. 20.2. Simplified scheme describing the central dogma in molecular biology. DNA is replicated and passed from one generation to the next. For protein biosynthesis, DNA sequence is first transcribed into complementary messenger RNA (mRNA) sequence which, by means of the adapter molecule transfer RNA (tRNA), is translated into protein sequence. The translation follows the genetic code where a nucleotide triplet (e.g., AGC) codes for an amino acid (e.g., serine) [522]...

By analogy to the terms co- and posttranslational modifications of peptides and proteins to define these transformations in the in vivo biosynthesis, chemical manipulations at least theoretically can be carried out in a co- or postsynthetic manner. While nature exploits the sequence- and even conformation-dependent regioselectivity of enzymes to expand the molecular and functional diversity of peptides and proteins beyond the genetic code,P l synthetic chemical reactions are insufficient for the required selectivity even with the most advanced conjugation techniques. Therefore, the tactics usually employed involves a cosynthetic approach, i.e. synthesis of polypeptide chains with annino acid derivatives or... 

The years 1961-65 wimessed a cascade of discoveries in the relationship between information stored in DNA and the structure and biosynthesis of proteins. In 1961, Marshall W. Nirenberg (1927- ), National Institutes of Health (NIH) in Bethesda, added polyuridylic acid (a synthetic pseudo-RNA) to cell-free preparations of mRNA-depleted E. coli ribosomes, mixed with enzymes and 18 different amino acids. The ribosomes used polyuridylic add in place of their own mRNA and synthesized the polypeptide polyphenylalanine. The first entry into the genetic code was therefore UUU in RNA coding for phenylalanine in protein. 

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