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.