chapter 11 lecture general, organic, and biological chemistry: an integrated approach laura frost,...

Chapter 11 Lecture

General, Organic, and Biological Chemistry: An Integrated Approach

Laura Frost, Todd Deal and Karen Timberlakeby Richard Triplett

© 2011 Pearson Education, Inc.

Nucleic Acids—Big Molecules with a Big Role

Chapter 11

Chapter 11 2© 2011 Pearson Education, Inc.

Chapter Outline

11.1 Components of Nucleic Acids

11.2 Nucleic Acid Formation

11.3 DNA

11.4 RNA and Protein Synthesis

11.5 Putting It Together: The Genetic Code and Protein Synthesis

11.6 Genetic Mutations

11.7 Viruses

11.8 Recombinant DNA Technology


Introduction

• DNA, deoxyribonucleic acid, is the molecule in our cells that stores and directs information responsible for cell growth and reproduction.

• DNA is found in the cell’s nucleus. It contains genetic information and is call the genome.

• A gene is one part of the genome, and contains information to make a particular protein for the cell.


Introduction

• DNA is long and stringy when isolated and can be seen with the naked eye.

• DNA and its counterpart ribonucleic acid, RNA, are made up of repeating building blocks called nucleotides.


11.1 Components of Nucleic Acids

• Nucleic acids are strings of molecules called nucleotides.

• Nucleic acids are created from a set of nucleotides in a given sequence.

• Each nucleotide has three basic components: 1. A nitrogenous base

2. A five-carbon sugar (pentose)

3. A phosphate functional group


11.1 Components of Nucleic Acids, Continued

• A nucleotide is shown as:

Nitrogenous Bases

• There are four nitrogenous bases in nucleic acids. Each contains either the purine ring or the pyrimidine ring.



• DNA contains two purines, adenine (A) and guanine (G), and two pyrimidines, thymine (T) and cytosine (C).

• RNA contains the same bases, except thymine is replaced with Uracil (U).



Ribose and Deoxyribose

• Nucleotides also contain five-carbon pentose sugars.

• RNA contains the pentose ribose (the “R” in RNA) and DNA contains the pentose deoxyribose (the “D” in DNA).

• Deoxyribose lacks the oxygen on carbon 2' of the pentose.



To distinguish between the carbons in the nitrogenous base from those in the sugar rings, a prime symbol (') is added to the carbons in the sugar ring.



Condensation of the Components

• A pentose and a nitrogenous base can join by a condensation reaction when a nitrogen in the base (N1 of pyrimidines and N9 of purines) bonds to the C1' of the pentose, forming a carbon-to-nitrogen glycosidic bond.

• When ribose condenses with the base adenine, a molecule called adenosine is formed.



Adenosine is referred to as a nucleoside because it lacks a phosphate group. All nucleosides are formed from condensation of the sugar pentose with a nitrogenous base.



• When a hydrogen phosphate (HPO42-) reacts

with the –OH on C5' of adenosine, a molecule known as a nucleotide is formed.

• The resulting molecule of this condensation is known as adenosine monophosphate, AMP.



Naming Nucleotides

• Nucleotides contain the name of the nucleoside and the number of phosphates present. An abbreviation is commonly used for the name.

• If deoxyribose is found in the nucleotide, a lower case d is inserted at the beginning of the abbreviation.



This table summarizes the names of the nucleosides and nucleotides found in RNA and DNA.



• Many nucleotides linked together form nucleic acids.

• Nucleotides are linked together through phosphodiester bonds, where the phosphate oxygens are connected between the 3' and 5' C’s of adjacent sugar molecules.

• The formation of a dinucleotide is shown on the next slide.


11.2 Nucleic Acid Formation, Continued



Primary Structure: Nucleic Acid Sequence

• A nucleic acid’s primary structure is indicated by its nucleotide sequence.

• The backbone of a nucleic acid consists of alternating sugar and phosphate with the bases dangling from the sugar.

• Phosphates are connected between the 3' carbon of one sugar and the 5' carbon of a neighboring sugar.



• The nucleotide sequence is designated by one-letter abbreviations.

• If a single nucleic acid strand is drawn horizontally, the 5' end of the nucleic acid is at the left end, and the 3' end is at the right end.


11.3 DNA

• Nucleic acid sequences, stored as DNA, code for cellular production of protein.

• The amount of adenine (A) is always equal to the amount of thymine (T), and the amount of cytosine (C) is always equal to the amount of guanine (G).

• The number of purines equals the number of pyrimidines.


11.3 DNA, Continued

Secondary Structure: Complementary Base

Pairing

• DNA’s secondary structure is described by the interaction of two nucleic acids to form a double helix as proposed by Watson and Crick in 1953.

• The double helix is described as a twisted ladder with the sugar–phosphate backbones making the rails and the bases dangling off the backbone, interacting to make the rungs in the center of the ladder.


11.3 DNA, Continued

The two strands are

antiparallel to each other,

with one strand going in

the 5' to 3' direction and

the other strand going in

the 3' to 5' direction.


11.3 DNA, Continued

• Each rung in the DNA ladder contains one base from each of the strands. The bases interact with each other through hydrogen bonding.

• All rungs are of the same length and consist of a purine and a pyrimidine. The pairs A–T and G–C are called complementary base pairs.

• Adenine forms two hydrogen bonds to thymine, and guanine forms three hydrogen bonds to cytosine. The DNA in one human cell contains about 3 billion of these base pairs.


11.3 DNA, Continued


11.3 DNA, Continued

Tertiary Structure: Chromosomes

• The compact structure of DNA, caused by the double helix twisting on itself, constitutes its tertiary structure. The further twisting of DNA is called supercoiling.

• The 3 billion base pairs of DNA in one human cell would stretch out as a double helix to about 6 feet in length.


11.3 DNA, Continued

• DNA in a human cell is separated into 46 pieces (23 from mother, 23 from father) that are supercoiled around proteins called histones.

• DNA pieces twist about histones and are packed into chromosomes. Chromosomes are an efficient package for large amounts of DNA information.


11.3 DNA, Continued



• RNA, like DNA, is a strand of nucleotides, and is responsible for protein synthesis.

• There are differences in the nucleotides of RNA and DNA.

• RNA does not contain thymine, instead it contains uracil. Uracil is complementary to adenine, and forms two hydrogen bonds with adenine.


11.4 RNA and Protein Synthesis, Continued

RNA Types and Where They Fit In

There are three types of RNA found in cells:1. Messenger RNA (mRNA)

2. Ribosomal RNA (rRNA)

3. Transfer RNA (tRNA)

• Messenger RNA and Transcription


11.4 RNA and Protein Synthesis, ContinuedMessenger RNA and Transcription

• The process of making protein requires two steps.• The first step is called transcription, which is a

process of making a gene copy from the DNA.• In transcription, DNA unwinds temporarily and a

complementary strand is made from one of the strands.

• This complementary copy is called the messenger RNA (mRNA).

• mRNA is a single strand of complementary bases of the original DNA, and copying is catalyzed by the enzyme RNA polymerase.

• mRNA travels to an organelle called the ribosome, where the mRNA sequence is processed into protein.



Ribosomal RNA and the Ribosome

• A ribosome is made up of ribosomal RNA (rRNA) and protein. It is the protein factory in the cell.

• Information in mRNA is interpreted into an amino acid sequence in the ribosome.



Ribosomal RNA and the Ribosome, Continued• Ribosomes are composed of two

rRNA/protein subunits called the small and large subunit.

• mRNA fits in a groove on the small subunit with the bases pointing toward the large subunit.



Transfer RNA and Translation• The second step in protein synthesis occurs

in the ribosome and is called translation.• Transfer RNA (tRNA) is the facilitator for this

process. • tRNA is T-shaped due to areas of hydrogen

bonding by complementary bases.• tRNA has a three-base sequence (triplet)

called an anticodon at its anticodon loop. • The anticodon hydrogen bonds to three

complementary bases on mRNA.



Transfer RNA and Translation, Continued• tRNA has a place on the opposite end of the

anticodon called the acceptor stem, where it can bind an amino acid through esterification.

• Each one of the 20 amino acids has one or more tRNAs that can transfer it to the ribosome for incorporation into a growing protein chain.



Transfer RNA and Translation, Continued


11.5 Putting It Together: The Genetic Code and Protein Synthesis

The Genetic Code

• A given triplet in mRNA contains a base sequence, transcribed from DNA, that translates to a specific amino acid. This triplet is called a codon.

• For example, the sequence UUU in a mRNA specifies the amino acid phenylalanine, GGG specifies glycine, and CGC specifies arginine.


11.5 Putting It Together: The Genetic Code and Protein Synthesis, Continued

• The tripeptide produced from the mRNA codons UUUGGGCGC is Phe–Gly–Arg.

• The genetic code assigns all 20 amino acids to codons of mRNA. There are 64 possible codon combinations from the four bases A, G, C, and U.



• The three codons UGA, UAA, and UAG are stop signals for protein synthesis.

• The triplet AUG serves two purposes in protein synthesis.

1. It represents the start codon initiating protein synthesis if it is at the 5' end of an mRNA.

2. It codes for the amino acid methionine if it is found elsewhere in mRNA.



Protein Synthesis

In review, protein synthesis involves:• Transcription, during which a complementary

copy of DNA, called mRNA, is created by RNA polymerase. mRNA travels out of the nucleus to the ribosome.

• tRNA activation, during which a tRNA synthetase attaches the correct amino acid to the acceptor stem of the tRNA.



In review protein synthesis involves:• Translation:

– Protein synthesis starts with the start codon.

– Activated tRNA, with methionine attached, enters the ribosome and hydrogen bonds to mRNA.

– The second activated tRNA, matching the next codon on mRNA, enters. The two amino acids join.

– The first tRNA leaves and the tRNA with the dipeptide attached shifts into the first position, a shifting called translocation.

– This process continues over and over until a protein chain emerges.



In review protein synthesis involves:• Termination:

– Eventually the ribosome encounters a stop

codon, and protein synthesis stops.

– The protein chain is released.

– The initial amino acid methionine is often

removed from the beginning of the chain.

– The protein chain folds into its tertiary

structure that makes it a biologically active

protein.



A change in a DNA nucleotide sequence is called a mutation. What happens to protein synthesis after a mutation?• No change in protein sequence. Only 2.5% of

DNA encodes for genes. The rest is “junk” DNA. These types of mutations are called silent mutations.

• A change in protein sequence occurs, but it has no effect on protein function. For example, a mutation may occur that results in an amino acid that has similar polarity and size to that of the original amino acid.


11.6 Genetic Mutations, Continued

A change in protein sequence occurs that affects protein function. For example, a mutation could occur that involves replacing a nonpolar amino acid with a polar amino acid. The structure and function of the resulting protein could change. A codon could be mutated to a stop codon. Bases could be inserted or deleted in a DNA strand.



Sources of Mutations

• Sometimes errors occur at random when DNA replicates itself. This is called a spontaneous mutation.

• Mutagens, like environmental agents or radiation can cause mutations.

• Sodium nitrite, used as a preservative in processed meats like hot dogs and bologna, is a chemical mutagen.



• Sodium nitrite, in the presence of amines, forms a compound known as a nitrosamine, known to cause cancer in animals.

• Mutations in somatic cells affects only the individual organism and can cause conditions like cancer.

• Mutations in germ cells (sperm or egg cells) can be passed on to future generations and can cause genetic diseases.


11.7 Viruses

• Viruses are small particles containing from 3 to 200 genes that can affect any type cell.

• Viruses are not considered cells because they cannot make their own proteins or energy.

• Viruses have their own nucleic acid, but use a host cell’s ribosome and RNA to make its proteins.


11.7 Viruses, Continued

• Viruses are very small and have a variety of shapes.

• Viruses contain a nucleic acid (DNA or RNA) enclosed in a protein coat called a capsid.

• Many viruses contain an additional coat called an envelope surrounding the capsid.



Viruses infect cells when an enzyme in the protein coat makes a hole in the host cell, allowing viral nucleic acid to enter and mix with the host cell material.



• If viral DNA is present, the host cell begins to replicate this DNA.

• Viral DNA produces viral RNA, which makes protein for the virus.

• Completed virus particles are assembled and released from the cell to infect more cells.

• This process occurs by a process called budding.



Vaccines are inactive forms of the virus that boost the immune response by causing the body to produce antibodies against the virus.



Retroviruses

• A virus that contains RNA as the nucleic acid is called a retrovirus.

• Once this RNA gets inside the cell, it makes viral DNA through a process known as reverse transcription.

• The complementary strands of viral DNA join the host DNA to make replicate virus particles.



HIV-1 and AIDS

• HIV-1 is a retrovirus responsible for AIDS.

• HIV-1 infects white cells known as T4 lymphocytes, which are part of the human immune system.

• Without the T4 lymphocytes, a person is unable to fight off infections like skin cancer, sarcomas, and pneumonia.



• Current AIDS therapies involve drugs that attach HIV-1 at the points of reverse transcription and viral protein synthesis.

• AZT, azidothymidine, is the first drug approved as an AIDS therapy. If it is incorporated into viral DNA by reverse transcriptase, transcription will not occur.

• Protease inhibitors are another class of drugs that have been approved to treat HIV-1.



• Protease inhibitors target a protein called HIV protease, which is responsible for clipping the viral proteins down to size for viral assembly.

• Protease inhibitors are competitive inhibitors that block the active site of HIV protease.

• Other drugs being developed are those that will block insertion of HIV-1 RNA into the host cell, and inhibitors that will block the enzyme involved in incorporating viral DNA into host DNA.



• Scientists have been finding ways to manipulate DNA to produce proteins needed as medicines, proteins helpful in crop resistance to pests, and proteins capable of positive identification of individuals.

• Recombinant DNA, also known as genetic engineering or gene cloning, involves recombining DNA from two different sources.

• This is done by inserting a higher organism’s gene into bacteria whose life cycle is shorter.


11.8 Recombinant DNA Technology, Continued

Using a shorter life cycle organism like bacteria allows for the production of large amounts of a desired protein more quickly.


11.8 Recombinant DNA Technology, ContinuedSteps involved in recombining DNA are as follows:

• Step 1. Identify and isolate a gene of interest, known as donor DNA. Removal is done with enzymes called restriction enzymes that recognize specific DNA sequences four to eight bases in length.

• Step 2. Insert donor DNA into the organism DNA using a vector. A vector is a transporter for the donor DNA. A common vector found in bacteria is a piece of circular DNA called a plasmid. Vector DNA is incorporated into the bacterial DNA as the bacteria grow.

• Step 3. Express the incorporated gene in the new organism. Bacteria will produce the protein coded for by the incorporated gene. This is called expression. The new protein can be isolated and purified.



Therapeutic Proteins

• The human insulin gene was the first application of recombinant DNA technology. It was incorporated into a bacteria called Escherichia coli.

• Insulin produced in this manner eliminated many of the side effects that occurred from the use of pig and cow insulin.



Genetically Modified Crops

• Recombinant technology is used to insert genes into crop and food plants offering many growth advantages.

• Cotton was the first crop that was modified by recombinant technology. By this method, cotton was made resistant to Roundup®, a weed killer.



• Another example of genetically modified crops is the Freedom II yellow squash.

• This squash contains genes to replicate viral coat proteins, allowing it to be resistant to viral infections.



Genetic Testing

• The entire human genome has been sequenced during a project known as the human genome project (HGP).

• Human genome contains over 3 billion base pairs and an estimated 20,000 to 25,000 genes.

• Because of HGP, genes responsible for many genetic diseases can be identified.



• Through genetic testing, a person’s DNA can be screened for mutated genes.

• These tests can assist couples planning to have children, identify paternity, and predict certain cancers, Alzheimer’s disease, and Huntington’s disease.



Nuclear Transplantation—Cloning an Organism

• Clone means to make an exact copy.

• Cloning an organism creates a genetic copy of the original organism.

• Cloning involves taking nuclear DNA from an adult cell and transplanting it into an egg whose DNA has been removed.



• This egg cell acts like a fertilized egg and will begin to divide, forming an embryo. This embryo can be transplanted and allowed to develop.

• Dolly the sheep, the first cloned animal, was born in 1996 after many attempts to implant an embryo.

• Since Dolly, many other animals including the cow, horse, monkey, deer, and cat have been cloned.


Chapter Summary11.1 Components of Nucleic Acids

• DNA and RNA are nucleic acids. They are made up of strings of nucleotides.

• A nucleotide is made up of three components: 1. A nitrogenous base

2. A five-carbon sugar3. A phosphate

• Deoxyribose is the sugar in DNA, and ribose is the sugar in RNA.


Chapter Summary, Continued


• The nitrogenous bases, adenine, thymine, cytosine, and guanine are present in DNA. In RNA, thymine is replaced by uracil.

• Nucleotides are named as the nucleoside plus the number of phosphates.

• Condensation reactions link the components of nucleosides, as well as those of nucleotides.




• The primary structure of each nucleic acid is its unique sequence.

• Nucleic acids form when nucleotides undergo condensation, linking sugar to phosphate.

• The 3' –OH on the sugar of a nucleotide condenses with the 5' phosphate of a neighboring nucleotide.




• The backbone of a nucleic acid consists of a sugar–phosphate to sugar–phosphate.

• The nitrogenous bases dangle from the backbone.

• Each nucleic acid has a single 5' to 3' end.



11.3 DNA

• A DNA molecule resembles a twisted ladder.

• DNA consists of two strands of nucleic acid running antiparallel to each other with their bases facing inward.

• Bases interact with one another through hydrogen bonding.



11.3 DNA, Continued

• Adenine forms two hydrogen bonds with thymine, and cytosine forms three hydrogen bonds with guanine.

• DNA is found in the nucleus of cells and is compacted into a tertiary structure called a chromosome.

• DNA supercoils itself around the protein histone.




• RNA differs from DNA in that it contains the base uracil instead of thymine, which hydrogen bonds to adenine.

• There are three types of RNA involved in transforming the DNA information into protein. They are:

1. Messenger RNA (mRNA)

2. Ribosomal RNA (rRNA)

3. Transfer RNA (tRNA)




• mRNA transcribes a complementary copy of DNA and takes it to the ribosome.

• Ribosomes are the site of protein synthesis. They consist of rRNA and protein.

• tRNA carries a specific amino acid to ribosomes. tRNA has two features: the anticodon at one end and the acceptor stem at the other end.



11.5 Putting It Together: The Genetic Code and

Protein Synthesis

• The genetic code is a series of base triplet sequences on mRNA specifying the amino acid sequence in a protein.

• The codon AUG signals the start of transcription and the codons UAG, UGA, and UAA signal it to stop.




Protein Synthesis, Continued

• Protein synthesis begins with transcription, where mRNA makes a complementary copy of a DNA gene.

• tRNA is activated by adding an amino acid to the acceptor stem.

• Translation involves bringing activated tRNA to the ribosome.




Protein Synthesis, Continued

• At the ribosome, peptide bonds are formed until a stop codon is reached.

• The polypeptide becomes a functional protein when it is released from the ribosome.




• Alterations of base sequences in DNA are called mutations.

• Some mutations are silent and do not affect protein synthesis, and some may change the amino acid sequence, but not the protein function.

• Some mutations change protein sequence, structure, and functions.




• Some mutations occur during DNA replication and are random.

• Some mutations are caused by mutagens in the environment. A mutation in a germ cell can be inherited causing a genetic disease.



11.7 Viruses

• Viruses contain DNA or RNA and a protein coat called a capsid.

• Viruses containing RNA are called retroviruses.

• HIV-1 is a retrovirus. Several drugs have been developed to slow down HIV-1 infection in AIDS patients.




• Recombinant DNA technology involves isolating a gene of interest from an organism and incorporating it into a second organism for the purpose of expressing a specific protein.

• The host organism can produce the protein of interest during transcription and translation.




• Recombinant DNA technology, gene cloning, has provided medicinal proteins, resistant crops, and identification of genetic diseases.

• Organism cloning involves making an exact copy of an organism.

chapter 11 lecture general, organic, and biological chemistry: an integrated approach laura frost,...

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