Chapter 17: Nucleic Acids and Protein Synthesis

17.1: Components of Nucleic Acids

• Nucleic Acids
    * Deoxyribonucleic acid (DNA)
    * Ribonucleic acid (RNA)
• Nucleotides: These are the repeating monomer units.
• Each nucleotide has three components:
    * A base
    * A five-carbon sugar
    * A phosphate group
• The nitrogen-containing bases in nucleic acids are derivatives of pyrimidine or purine.
    * In DNA, the purine bases with double rings are adenine (A) and guanine (G); and the pyrimidine bases with single rings are cytosine (C) and thymine (T).
    * RNA contains the same bases, except thymine (T) is replaced by uracil (U).

• Ribose: The five-carbon sugar in RNA which gives the letter R in the abbreviation of RNA.
• Deoxyribose: The five-carbon sugar in DNA, is similar to ribose except that there is no hydroxyl group.
• Nucleosides: A combination of sugar and a base, is produced when the nitrogen atom in a pyrimidine or a purine base forms an N-glycosidic bond to carbon 1 of sugar, either ribose or deoxyribose.

• Nucleotides: These are nucleosides in which a phosphate group bonds to the —OH group on carbon 5 of ribose or deoxyribose.

Naming Nucleosides and Nucleotides

17.2: Primary Structure of Nucleic Acids

• Nucleic Acids: These are polymers of many nucleotides in which the 3′-hydroxyl group of the sugar in one nucleotide bonds to the phosphate group on the 5′-carbon atom in the sugar of the next nucleotide.
• Phosphodiester bond: The link between the sugars in adjacent nucleotides.
• Primary Structure of Nucleic Acid: It is this sequence of bases that carries the genetic information from one cell to the next.
    * In any nucleic acid, the sugar at the one end has an unreacted or free 5′-phosphate terminal end, and the sugar at the other end has a free 3′-hydroxyl group.

17.3: DNA Double Helix

• During the 1940s, biologists determined that the bases in DNA from a variety of organisms had a specific relationship: the amount of adenine (A) was equal to the amount of thymine (T), and the amount of guanine (G) was equal to the amount of cytosine (C).
• Eventually, scientists determined that adenine is always paired (1:1) with thymine, and guanine is always paired (1:1) with cytosine.
• In 1953, James Watson and Francis Crick proposed that DNA was a double helix that consisted of two polynucleotide strands winding about each other like a spiral staircase.
• Complementary Base Pairs: The pairs AT and GC;
    * These are the specific pairing of the bases occur because adenine and thymine form only two hydrogen bonds, while cytosine and guanine form three hydrogen bonds.

• DNA Replication
    * The strands in the original or parent DNA molecule separate to allow the synthesis of complementary DNA strands.
    * The process begins when helicase catalyzes the unwinding of a portion of the double helix by breaking the hydrogen bonds between the complementary bases.
    * The resulting single strands act as templates for the synthesis of new complementary strands of DNA.

17.4: RNA and the Genetic Code

• RNA: It makes up most of the nucleic acid found in the cell, is involved with transmitting the genetic information needed to operate the cell.
• RNA molecules are polymers of nucleotides as well.

• RNA differs from DNA in several important ways:
    * The sugar in RNA is ribose rather than the deoxyribose found in DNA.
    * In RNA, the base uracil replaces thymine
    * RNA molecules are single-stranded, not double-stranded.
    * RNA molecules are much smaller than DNA molecules.
• Ribosomal RNA (rRNA): The most abundant type of RNA is combined with proteins to form ribosomes.
    * Ribosomes, which are the sites for protein synthesis, consist of two subunits: a large subunit and a small subunit.
• Messenger RNA (mRNA): It carries genetic information from the DNA, located in the nucleus of the cell, to the ribosomes located in the cytoplasm.
• Transfer RNA (tRNA): The smallest of the RNA molecules interprets the genetic information in mRNA and brings specific amino acids to the ribosome for protein synthesis.
    * Anticodon: A series of three bases that complements three bases on mRNA.
    * Transcription: Genetic information for the synthesis of a protein is copied from a gene in DNA to make mRNA.
    * Translation: tRNA molecules convert the information in the mRNA into amino acids, which are placed in the proper sequence to synthesize a protein.

• Genetic Code: It consists of a series of three nucleotides in mRNA called codons that specify the amino acids and their sequence in the protein.

Genetic Codes of Amino Acid

17.5: Protein Synthesis

• Protein Synthesis
    * Once the mRNA is synthesized, it migrates out of the nucleus into the cytoplasm to the ribosomes.
    * In the translation process, tRNA molecules, amino acids, and enzymes convert the codons on mRNA to build a protein.
• Activation of tRNA: It occurs when aminoacyl–tRNA synthetase forms an ester bond between the carboxylate group of its amino acid and the hydroxyl group on the acceptor stem.

• Initiation and Chain Elongation
    * The first codon in mRNA is a start codon, AUG, which forms hydrogen bonds with methionine–tRNA.
    * Another tRNA hydrogen bonds to the next codon, placing a second amino acid adjacent to methionine.
    * A peptide bond forms between the C-terminal of methionine and the N-terminal of the second amino acid
    * Translocation: The initial tRNA detaches from the ribosome, which shifts to the next available codon.
    * During chain elongation, the ribosome moves along the mRNA from codon to codon, so that the tRNAs can attach new amino acids to the growing protein chain.
    * Sometimes, polysome translates the same strand of mRNA to produce several copies of the protein at the same time.

• Chain Termination
    * Stop codons: These are encountered which the termination of protein synthesis and the release of the protein chain from the ribosome.

17.6: Genetic Mutations

• Mutation: A change in the nucleotide sequence of DNA.
    * Such a change may alter the sequence of amino acids, affecting the structure and function of a protein in a cell.
    * If a mutation occurs in a somatic cell, the altered DNA will be limited to that cell and its daughter cells.
    * If the mutation causes uncontrolled growth, cancer could result.
    * If a mutation occurs in a germ cell, then all the DNA produced in a new individual will contain the same genetic change.
    * When a mutation severely alters the function of structural proteins or enzymes, the new cells may not survive or the person may exhibit a genetic disease.

• Point Mutation: The replacement of one base in the template strand of DNA with another.
• Silent Mutation: This occurs if a substitution gives a codon for the same amino acid, and there is no change in the amino acid sequence in the protein.
• Frameshift Mutation: A base is inserted into or deleted from the normal order of bases in the template strand of DNA.
• Genetic Disease: It is the result of a defective enzyme caused by a mutation in its genetic code.

Normal DNA and protein synthesis

Substitution of one base

Frameshift mutation caused by the deletion of a base

List of some Common Genetic Diseases

• Galactosemia: The transferase enzyme required for the metabolism of galactose-1-phosphate is absent, resulting in the accumulation of galactose-1-phosphate.
    * It leads to cataracts and mental retardation.
• Cystic fibrosis: It is caused by a mutation in the gene for the protein that regulates the production of stomach fluids and mucus
    * It is one of the most common inherited diseases in children, in which thick mucus secretions make breathing difficult and block pancreatic function.
• Down syndrome: It is the leading cause of mental retardation, occurring in about 1 of every 800 live births; the mother’s age strongly influences its occurrence.
    * Mental and physical problems, including heart and eye defects, are the result of the formation of three chromosomes, usually under number 21, instead of a pair.
• Familial hypercholesterolemia: It occurs when there is a mutation of a gene on chromosome 19, which produces high cholesterol levels.
    * This usually lead to early coronary heart disease in people 30 to 40 years old
• Muscular dystrophy: It is caused by a mutation in the X chromosome.
    * This muscle-destroying disease appears at about age 5, with death by age 20, and occurs in about 1 of 10 000 males.
• Huntington’s disease: It affects the nervous system, leading to total physical impairment.
    * It is the result of a mutation in a gene on chromosome 4, which can now be mapped to test people in families with a history of HD.
• Sickle-cell anemia: It is caused by a defective form of hemoglobin resulting from a mutation in a gene on chromosome 11.
    * It decreases the oxygen-carrying ability of red blood cells, which take on a sickled shape, causing anemia and plugged capillaries from red blood cell aggregation.
• Hemophilia: It is the result of one or more defective blood-clotting factors that lead to poor coagulation, excessive bleeding, and internal hemorrhages.
• Tay–Sachs disease: It is the result of defective hexosaminidase A, which causes an accumulation of gangliosides and leads to mental retardation, loss of motor control, and early death.

17.7: Viruses

• Viruses
    * These are small particles of 3 to 200 genes that cannot replicate without a host cell
    * It does not have the necessary material such as nucleotides and enzymes to make proteins and grow.
    * The only way a virus can replicate is to invade a host cell and take over the machinery and materials necessary for protein synthesis and growth.
• Viral Infection
    * It begins when an enzyme in the protein coat of the virus makes a hole in the host cell, allowing the viral nucleic acids to enter and mix with the materials in the host cell.
    * If the virus contains DNA, the host cell begins to replicate the viral DNA in the same way it would replicate normal DNA.

• Reverse Transcription
    * It is a process that occurs once inside the host cell, it must first make viral DNA.
    * Retrovirus: A virus that contains RNA as its genetic material.
    * Reverse transcriptase: An polymerase enzyme in a retrovirus that uses the viral RNA template to synthesize complementary strands of DNA.
    * Provirus: A newly formed DNA that integrates with the DNA of the host cell.

• Acquired Immune Deficiency Syndrome
    * HIV-1 Virus: Known to be the AIDS-causing agent.
    * HIV: A retrovirus that infects and destroys T4 lymphocyte cells, which are involved in the immune response.
    * AIDS is characterized by opportunistic infections such as:
      * Pneumocystis carinii
      * Kaposi’s sarcoma
    * Treatment of AIDS often combines reverse transcriptase inhibitors with protease inhibitors such as saquinavir, indinavir, fosamprenavir, nelfinavir, and ritonavir.