In the study of biology, one finds that seemingly simple processes are often some of the most complicated processes. For example, why is an individual's skin a certain colour? Why are their eyes a particular colour, and why is their hair straight or curly? These variations are the results of an important process known as protein synthesis. Protein synthesis refers to the production of amino acid polymers within the cells. What are the substances required for synthesis? Where in the cell does it take place, how does it occur, and what happens if something in the process goes wrong? All of these questions will be answered in this paper.
In order to appreciate the magnitude of the complexity of protein synthesis, it is useful to briefly examine protein role and structure. Proteins have been said to be one of the most important biochemical molecules. Proteins are the basic substances for the major structural components of biological tissue. Yet, proteins are not the most basic of all substances. They are natural polymer molecules, made up of amino acids. There are twenty-six amino acids found in the body, with the number of acids themselves in a protein ranging from two to several thousand. The sequence and number of amino acids determines which protein is formed and the way it will function. But what determines this information? 7
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The biochemical molecule that determines everything in the process of protein synthesis is DNA. DNA is short for Deoxyribonucleic Acid. DNA is shaped as a double helix, and one of the main and most important functions of DNA is to initiate and control protein synthesis. DNA itself resides in the nucleus of a cell. DNA is composed of sequences of nucleotides, which themselves are made up of a sugar, a phosphate, and a nitrogen base. The nitrogen bases make up the rungs of the DNA's twisted-ladder like structure, with the sugar and phosphate forming the backbone of the helices.4 There are four nitrogen bases that are used in DNA, and they can be classified as either purine or pyrimidine.7
Purine bases have both a six and five member ring. Pyrimidines have only the six member ring. The two purines are known as adenine and guanine. The two pyrimidines are called cytosine and thymine. It should be noted that that another pyrimidine called uracil takes the place of thymine in RNA (RNA itself will be analyzed shortly). In DNA the bases form base pairs using hydrogen bonding. A purine on one helix will bond with the corresponding pyrimidine on the other helix. Adenine corresponds to thymine, while guanine corresponds to cytosine. The sequence of nucleotides provides the code which determines the amino acids to be linked together for a specific protein. However, the DNA remains in the nucleus of the cell. Therefore, a messenger is required to bring the information in the DNA to the organelles that perform the required protein synthesis. 4, 7
Another substance that is crucial to the process of protein synthesis is RNA. RNA is short for Ribonucleic Acid and is located in a cell's cytoplasm. There are three types of RNA , of which one, called mRNA, is the "messenger" which brings the DNA information out of the nucleus to other organelles. It carries the codes contained in the DNA that specify the particular sequence of amino acids that must be built in order to form proteins. Transfer RNA, or tRNA, is another form of RNA. In the process of protein synthesis, tRNA will read the codes in the mRNA. It then uses this information to select the correct amino acid to be used in the construction of the protein. Lastly, ribosomal RNA, or rRNA, binds with proteins to form ribosomal subunits, which attach to the mRNA.
What has just been described are some of the basic chemicals involved in protein synthesis. But there is the process of protein synthesis itself. This will now be examined in detail. The first step in this process is known as transcription, and refers to the process of mRNA encryption off of DNA. The second step of the process is called translation. This refers to the processing of the information on the mRNA to form proteins.
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First in transcription, DNA within the nucleus unwinds, with a specific enzyme named RNA polymerase aiding the process. The nucleotides from RNA, coming from a pool within the nucleus, join with one strand of the DNA that has been unzipped. The base of the DNA nucleotide determines which RNA nucleotide attaches to it, as described previously in the discussion of base pairs. The RNA polymerase then joins the RNA nucleotides together. The end result is a molecule of mRNA. However, this mRNA is known as primary mRNA, which has not yet been processed to become mature mRNA.
The DNA carries the genes of the particular organism. However, not all of the nucleotides within the DNA code for parts of genes. These sections of DNA are known as introns. The parts of the DNA that are part of the genes are known as exons. Because only the exons are part of the genes, it is only that information that is used to form proteins. Since mRNA contains all of the information of the DNA, it includes both the introns and exons. Therefore, the mRNA must undergo processing before it leaves the nucleus, to remove the introns from the mRNA while keeping the exons. However, there cannot be gaps in a strand of mRNA. So the parts of the mRNA that are not to be removed, the exons, are joined to form a strand of mRNA that is not broken.
However, the mRNA strand cannot split itself. The work of splitting the mRNA is left to enzymes called ribozymes, which are made up of RNA themselves! Therefore, RNA based enzymes split the RNA and stitch the exons back together. The processing of mRNA usually and ordinarily consolidates the exons of genes. However, the splicing of mRNA in some specific cases results in only some exons being consolidated. Because of this process, a different kind of mRNA can be produced. This different mRNA will allow the cell to produce related but different proteins. In either case, the mRNA leaves the nucleus and travels to the endoplasmic reticulum in the cytoplasm.
At this point, translation takes place. In this step, the sequence of amino acids in a protein coded for by the specific patterns of nucleotides in the mRNA is determined. The mRNA nucleotides are organized into specific sequences called codons. Each codon is made up of a specific sequence of three nucleotides. Each combination of nucleotides codes for a specific amino acid. Because there are twenty-six amino acids and only four bases, it is clear that three bases are required to code for an amino acid. There are sixty-four different codons possible (three nucleotide groups, four possibilities for each group). Hence, there may be more than one codon for a particular amino acid.
The mRNA codons have corresponding tRNA anticodons. An example illustrating the relationship between codon and anticodon follows: If the codon is ACC, the correct anticodon will be UGG. This codes for the amino acid threonine. The pattern of the codons codes for a specific anticodon that is in turn linked to a specific amino acid. Since amino acids build proteins, this coding is very important.
Amino acids are brought to the ribosomes by the tRNA. The tRNAs are single stranded nucleic acids, which fold back on themselves to form a boot shape. This shape is the result of base pairing within the single strand. For each of the twenty amino acids found in proteins there are distinct tRNAs. An amino acid connects to the tRNA at the toe of the boot. An anticodon is located at the opposite end of the tRNA. It is still in question as to how the specific amino acids connect to their specific tRNA molecules. It is also in question as to how the mRNA and tRNA are transported to the ribosomal subunits.
Chain initiation refers to the first amino acid attached to its tRNA being associated with the mRNA initiation codon. There is a particular codon, AUG, that codes for the beginning of a protein. This codon codes for the amino acid methionine, which universally represents the start of a protein. A small ribosomal subunit, a large ribosomal subunit, an initiator tRNA (carrying methionine), and an mRNA join together. The small ribosomal subunit attaches to the mRNA in the area around the location of the AUG. The tRNA with the anticodon UAC attaches to the AUG codon. The tRNA is able to do this because it has a protein, eIF-2, that enables it to identify the AUG codon. Then the small ribosomal subunit pairs up with the large ribosomal subunit. 1, 2, 3, 4, 5, 6
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The process which forms ribosomal subunits is crucial to the process of protein synthesis itself as well. It starts with rRNA. Because the rRNA is found in the ribosomes, it is known as structural RNA. rRNA is produced in the nucleolus within eukaryotic cells. Within the nucleolus it joins with proteins that were built in the cytoplasm, causing the creation of two ribosomal subunits. One subunit is large (60S), and the other is small (40S). The subunits each contain several different proteins, as well as an rRNA molecule. Ribosomes have two binding sites for two tRNA, and they are called binding sites because the codon of mRNA is bound to the anticodon of tRNA.
The next step in the process of protein synthesis is chain elongation. The tRNA that is first at the binding site has a peptide attached to it in most cases. The reason for this is because the initiator tRNA transfers its own amino acid to a tRNA-amino acid complex
that comes to the second binding site. Now the ribosome moves, resulting in the tRNA that was at the second binding site being at the first binding site. This process is known as translocation.
Another ribosome may attach to the mRNA after the first ribosome has already translocated down the mRNA. The first ribosome at this point has already done some initial translation of the mRNA. It is possible for several ribosomes to be translating the same strand of mRNA at the same time. These ribosomes would form a structure that is known as a polyribosome.
Translocation occurs multiple times during the process of chain elongation. Each time translocation occurs the ever growing polypeptide is moved to the new amino acid that has arrived, being attached to it by a peptide bond. The moving of the polypeptide to the new amino acid requires a ribozyme and energy. The ribozyme is part of the larger ribosomal subunit. The tRNA molecule picks up a new amino acid at the end of translocation and then goes back to the ribosome. Once the amino acid is removed from the tRNA, the tRNA detaches.
This whole cycle, which includes complementary base pairing of the new tRNA, transfer of peptide chain, and translocation is done at a very rapid rate. For example, the cycle is done 15 times every second in Escherichia coli bacteria.
At the end of the process of protein synthesis chain termination occurs. The action of the termination occurs when a codon that does not code for an amino acid, known as a stop codon, is reached. There are three known stop codons, known as UAA, UAG, and UGA. The polypeptide that was in involved in the protein synthesis is removed enzymatically from the last tRNA by a particular release factor. The ribosome now separates into its two subunits while the tRNA and polypeptide leave.
Under ideal circumstances, the above process of protein synthesis perfectly without any errors. However, problems can occur during protein synthesis, given undesirable circumstances. They can start with "bad genes." Sometimes the DNA is not defective simply because it is inherited. Sometimes outside circumstances can affect the DNA. Radiation is a good example. If a person is exposed to enough radiation, the radiation changes their DNA composition. Mutations can occur as an error in the system. As a result, organisms can develop abnormalities within a few months, a few years, or a few decades. Also, since the DNA is damaged, the individual's offspring also have defective DNA. The effects of Nagasaki, Hiroshima, and Chernobyl have shown this.
However, nuclear bomb or power plant fallout is not the only external force that can mutate DNA. Too much UV light from sources such as the sun can also cause DNA mutations. That is one of the reasons people war sunscreen at the beech. Heavy metals such as plutonium or radium can also give off radiation that can hurt the genetics of an organism. All of these different sources of radiation have been known to distort the genetic code enough to cause fatal cancers and mutations within the individual and their offspring.
There can also be genes that have been wrongly turned "on" or "off." As a result, they either code for something the body does not need, or they do not code for something the body does require. As a result, different proteins are produced than what is required.
Sometimes these problems are fairly isolated and are of no consequence. The individual does not notice anything wrong, and neither does anyone they associate with. An example of mutation that is fairly benign is that of albinism, in which the genes in an individual do not produce pigment. As a result the person's external appearance is that of being totally white. This may be virtually unnoticed if the individual resides with a very light skinned, blond haired population. However, if this individual lives in rural Tanzania, the pigment problem causes the individual to be shunned by his/her tribe and clan, which leaves them vulnerable.
At other times, what these defective genes code for is critical, and the results are devastating for the individual. For example, defective DNA can cause brain damage, resulting in mental disabilities. Other times, the bad genes affect the physical external part of the body. This can include an extra amount of toes, arms, legs, fingers, or a lack of these. Another example of a protein synthesis malfunction which has severe implications to the individual would be that of cystic fibrosis. The malfunction of protein
synthesis affects the organism's lungs, shortening their lifespan by about 60%-70%. Familial cancers are another example of seemingly simple processes gone awry.
As shown, the process of protein synthesis a critical process in organisms, from cells to human beings. It codes for traits unique to the specific organism, like hair and eye colour. It also codes for traits generically of the particular species. These traits can include blood types and hormones. Protein synthesis is at the root of all of an organism's functions and appearance. It has life or death effects. The process is incredibly sophisticated, and there is still much research to be done on it. 8