7 Биосинтез белка (1160076)
Текст из файла
Лекция 7.Биосинтез белкаP A R TInformation Pathways789790Part IV Information PathwaysReplicationDNATranscriptionfRNATranslationfProteinThe central dogma of molecular genetics, showingthe general pathways of information flow via theprocesses of replication, transcription, and translation. The term "dogma" is a misnomer here. It wasintroduced by Francis Crick at a time when littleevidence supported these ideas. The "dogma" is nowa well-established principle.DNA molecules having identical nucleotide sequences.
The second istranscription, the process by which parts of the coded genetic message in DNA are copied precisely in the form of RNA. The third istranslation, in which the genetic message coded in messenger RNA istranslated on the ribosomes into a protein with a specific sequence ofamino acids.Part IV is devoted to an explanation of these and related processes.First (Chapter 23) we will examine the structure, topology, and packaging of chromosomes and genes. The processes that make up the central dogma will be elaborated in Chapters 24 through 26.
Then, as wehave done for biosynthetic pathways, we will turn to regulation andexamine how the expression of genetic information is controlled (Chapter 27).A major theme running through these chapters is the added complexity encountered in the biosynthesis of a macromolecule when thatmacromolecule contains information.
Assembling nucleic acids andproteins with the correct sequences of nucleotides and amino acids,respectively, represents nothing less than preserving the faithful expression of the template upon which life itself is based. The formationof phosphodiester bonds in DNA or peptide bonds in proteins might beexpected to be a trivial feat for cells, given the arsenal of enzymatic andchemical tools described in Part III of this book.
Nevertheless, theframework of patterns and rules established in the examination ofmetabolic pathways must be enlarged considerably when informationis added to the equation. Forming specific bonds and preventing sequence errors in these polymers has an enormous impact on the thermodynamics, chemistry, and enzymology of the synthetic processes.For example, formation of a peptide bond should require an input ofonly about 21 kJ, and relatively simple enzymes that catalyze comparable reactions are known.
To synthesize the correct peptide bond between two specific amino acids at a given point in a protein, however,the cell invests about 125 kJ in chemical energy and makes use of thecombined activities of over 200 RNA molecules, enzymes, and specialized proteins. Information is expensive.The dynamic interaction between nucleic acids and proteins is another central theme of Part IV. With the important exception of a fewcatalytic RNA molecules (discussed in Chapter 25), the processes thatmake up the pathways of cellular information flow are catalyzed andregulated by proteins. An understanding of these enzymes and proteins can have practical as well as intellectual rewards because theyform the basis of the development of recombinant DNA technology.This technology is making possible the prenatal diagnosis of geneticdisease; the production of a wide range of potent new pharmaceuticalagents; the sequencing of the entire human genome; the introductionof new traits into bacteria, plants, and animals for industry and agriculture; human gene therapy; and many other advances.
We finish ourtour of the information pathways, and indeed the entire book, in Chapter 28 with a look at this technology and its implications for the future.C H A P T E RProtein MetabolismProteins are the end products of most information pathways. A typicalcell requires thousands of different proteins at any given moment.These must be synthesized in response to the cell's current needs,transported (targeted) to the appropriate cellular location, and degraded when the need has passed. The protein synthesis pathway ismuch better understood than protein targeting or degradation, andcoverage in this chapter reflects that fact.Protein synthesis is the most complex of biosynthetic mechanisms,and understanding it has been one of the greatest challenges in thehistory of biochemistry. In eukaryotic cells, protein synthesis requiresthe participation of over 70 different ribosomal proteins; 20 or moreenzymes to activate the amino acid precursors; a dozen or more auxiliary enzymes and other specific protein factors for the initiation, elongation, and termination of polypeptides; perhaps 100 additional enzymes for the final processing of different kinds of proteins; and 40 ormore kinds of transfer and ribosomal RNAs.
Thus almost 300 differentmacromolecules must cooperate to synthesize polypeptides. Many ofthese macromolecules are organized into the complex three-dimensional structure of the ribosome to carry out stepwise translocation ofthe mRNA as the polypeptide is assembled.To appreciate the central importance of protein synthesis to everycell, it can be enlightening to consider the fraction of cellular resourcesthat are devoted to this process.
Protein synthesis can account for up to90% of the chemical energy used by a cell for all biosynthetic reactions.In E. coli, the numbers of different types of proteins and RNA molecules involved in protein synthesis are similar to those in eukaryoticcells. Both prokaryotic and eukaryotic cells contain thousands of copiesof each protein and RNA type per cell. When totaled, the 20,000 ribosomes, 100,000 related protein factors and enzymes, and 200,000tRNAs present in a typical bacterial cell (with a volume of 100 nm3) canaccount for more than 35% of the cell's dry weight.Despite this great complexity, proteins are made at exceedinglyhigh rates.
A complete polypeptide chain of 100 residues is synthesizedin a n £ . coli cell at 37 °C in about 5 s. The synthesis of the thousands ofdifferent proteins in each cell is tightly regulated so that only the required number of molecules of each is made under any given set ofmetabolic circumstances. To maintain the appropriate mix and concentration of proteins in a cell, the targeting and degradative processesmust keep pace with synthesis. Research is gradually unraveling theChapter 26 Protein Metabolism893extraordinary set of biochemical processes that shepherd each proteinto its proper location in the cell and selectively degrade proteins nolonger required.Protein Synthesis and the Genetic CodeThree major advances in the 1950s set the stage for our present knowledge of protein biosynthesis.
In the early 1950s Paul Zamecnik and hiscolleagues designed a set of experiments to investigate the question:Where in the cell are proteins synthesized? They injected radioactiveamino acids into rats, and at different time intervals after the injectionthe liver was removed, homogenized, and fractionated by centrifugation. The subcellular fractions were then examined for the presence ofradioactive protein. When hours or days were allowed to elapse afterinjection of the labeled amino acids, all the subcellular fractions contained labeled proteins. However, when the liver was removed andfractionated only minutes after injection of the labeled amino acids,labeled protein was found only in a fraction containing small ribonucleoprotein particles.
These particles, earlier discovered in animal tissuesby electron microscopy, were thus identified as the site of protein synthesis from amino acids; later they were named ribosomes (Fig. 26-1).The second advance was made by Mahlon Hoagland and Zamecnik; they found that when incubated with ATP and the cytosolic fraction of liver cells, amino acids became "activated." The amino acidswere attached to a special form of heat-stable soluble RNA, later calledtransfer RNA (tRNA), to form aminoacyl-tRNAs. The enzymes catalyzing this process are the aminoacyl-tRNA synthetases.The third major advance occurred when Francis Crick asked: Howis the genetic information that is coded in the 4-letter language of nucleic acids translated into the 20-letter language of proteins? Crickreasoned that tRNA must serve the role of an adapter, one part of thePaul ZamecnikFigure 26-1 Electron micrograph and schematicdrawing of a portion of a pancreatic cell, showingribosomes attached to the outer (cytosolic) face ofthe endoplasmic reticulum.
The ribosomes are thenumerous small dots bordering the parallel layersof membranes.894Part IV Information PathwaysAmino acidmoleculeFigure 26-2 Crick's hypothesis of the adapterfunction of tRNA. Today we know that the aminoacid is covalently bound at the 3' end of the tRNAand that a specific nucleotide triplet elsewhere inthe tRNA molecule interacts with a specific tripletcodon in the mRNA through hydrogen bonding ofcomplementary bases.Amino acidbinding siteAdapter (tRNA)mRNANucleotide tripletcoding for anamino acidtRNA molecule binding a specific amino acid and some other part ofthe tRNA recognizing a short nucleotide sequence in the mRNA codingfor that amino acid (Fig.
26-2). This idea was soon verified. The tRNAadapter "translates" the nucleotide sequence of an mRNA into theamino acid sequence of a polypeptide. The overall process of mRNAguided protein synthesis is often referred to simply as translation.These developments soon led to recognition of the major stages ofprotein synthesis and ultimately to the elucidation of the genetic codewords for the amino acids. The nature of this code is the focus of thediscussion that follows.The Genetic Code Has Been SolvedBy the 1960s it had long been apparent that at least three nucleotideresidues of DNA are required to code for each amino acid. The four codeletters of DNA (A, T, G, and C) in groups of two can yield only 4 2 = 16different combinations, not sufficient to code for 20 amino acids.
Butfour bases in groups of three can yield 4 3 = 64 different combinations.Early genetic experiments conclusively proved not only that the genetic code words or codons for amino acids are triplets of nucleotidesbut also that the codons do not overlap and there is no punctuationbetween codons for successive amino acid residues (Figs. 26-3, 26-4).Figure 26—3 The triplet, nonoverlapping code. Evidence for the general nature of the genetic codecame from many types of experiments, includinggenetic experiments on the effects of deletion andinsertion mutations.
Характеристики
Тип файла PDF
PDF-формат наиболее широко используется для просмотра любого типа файлов на любом устройстве. В него можно сохранить документ, таблицы, презентацию, текст, чертежи, вычисления, графики и всё остальное, что можно показать на экране любого устройства. Именно его лучше всего использовать для печати.
Например, если Вам нужно распечатать чертёж из автокада, Вы сохраните чертёж на флешку, но будет ли автокад в пункте печати? А если будет, то нужная версия с нужными библиотеками? Именно для этого и нужен формат PDF - в нём точно будет показано верно вне зависимости от того, в какой программе создали PDF-файл и есть ли нужная программа для его просмотра.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
