- No category
Nucleic Acids & Proteins: Biomedical Engineering Presentation
advertisement
INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Presenter Sasha-Gay Wright INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 § Nucleic Acids and Proteins INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms Nucleic Acids One of the family of large molecules which includes deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Nucleic Acids Why that name? • Nucleic acids were so named because they were first found in the nucleus of cells, but they have since been discovered also to exist outside the nucleus and were also found to be slightly acidic. • The monomer of nucleic acid is called a nucleotide. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Nucleotide -This is one of the structural components, or building blocks, of DNA and RNA. -A nucleotide consists of a base, a molecule of sugar and a phosphate group. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Nucleotide How does DNA and RNA differ? 1. The pentose sugar Polymers that have deoxyribose (pentose sugar) are DNA molecules whereas polymers with ribose sugar make up RNA molecules. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Nucleotide INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Nucleotide How do they differ? 2. The base that is attached to the nucleotide can be one of five chemicals: adenine, thymine (DNA), guanine, cytosine and uracil (RNA). INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 The Bases The bases are categorized as Purine or Pyrimidine based on the rings in their structure. A and G are purine bases (contains two rings) while C, T and U are pyrimidine bases (contains one ring). INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms • Polynucleotide What is a Polynucleotide? A polynucleotide is a chain of nucleotides. RNA is a polynucleotide, and DNA is a pair of polynucleotides. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Polynucleotide To form a polynucleotide, the phosphate of one nucleotide binds to the pentose sugar of another via a phosphodiester bond. The reaction is catalyzed by an enzyme, polymerase. The Nitrogenous base binds to pentose sugar via a glycosidic bond. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Polynucleotide INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms • DNA DNA is a polymer of nucleotides which are joined through a backbone of alternating phosphate and deoxyribose sugar residues. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms DNA • Their nitrogen-containing bases occur in complementary pairs as determined by their ability to form hydrogen bonds between them (complementary base pairing). • A always pairs with T through two hydrogen bonds • G always pairs with C through three hydrogen bonds. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms DNA The spans of A:T and G:C hydrogen-bonded pairs are nearly identical, allowing them to bridge the sugarphosphate chains uniformly. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms DNA This structure, along with the molecule’s chemical stability, makes DNA the ideal genetic material. The bonding between complementary bases also provides a mechanism for the replication of DNA and the transmission of genetic information. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms DNA The double polynucleotide chains in DNA are said to be anti-parallel. This is because the two strands, though identical, run in opposite directions as determined by the orientation of the 5ʹ to 3ʹ phosphodiester bond. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms DNA The double helical structure of normal DNA takes a right-handed form called the B-helix. The helix makes one complete turn approximately every 10 base pairs. B-DNA has two principal grooves, a wide major groove and a narrow minor groove. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms DNA The double helical structure places the non-polar bases of DNA in the center of the double-stranded molecule, surrounded by the charged phosphate groups. This has two functional consequences; üThe double-helix structure, with negatively charged phosphates on the outside edges. Therefore, it allows the phosphates to be as far apart as possible. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Typical Phosphate molecule INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms DNA üThe cellular environment is aqueous and therefore polar, so surrounding the non-polar bases with charged phosphates maximizes the solubility of DNA under physiological conditions. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 • In order to fit within the nucleus, DNA is packed into tightly coiled structures called chromatin. • Chromatin condenses to form chromosomes during cell division. • Histones: The chief protein components of chromatin, acting as spools around which DNA winds, and playing a role in gene regulation. • Nucleosome: a structural unit of a eukaryotic chromosome, consisting of a length of DNA coiled around a core of histones. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 What is the purpose of DNA? üCarries a code that is used by the cell when making proteins. -The sequence of bases in the DNA molecules determines the sequence of Amino Acid that are strung together when a protein molecule is being made. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms Codon üA set of three adjacent nucleotides, also called triplet. Eg ATG üEach codon codes for a special Amino Acid. Eg. ATG codes for the A.A Methionine. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms Amino Acid What are Amino Acids? üAmino acid, any of a group of organic molecules that consist of a basic amino group (―NH2), an acidic carboxyl group (―COOH), and an organic R group (or side chain) that is unique to each amino acid INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 AMINO ACID BASIC STRUCTURE INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Polypeptide What are Polypeptides? üA linear organic polymer consisting of a large number of amino-acid residues bonded together in a chain, forming part of (or the whole of) a protein molecule. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DIPEPTIDE BASIC STRUCTURE INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms Gene üThe length of DNA that codes for making one polypeptide. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Key terms • RNA What is RNA? RNA is a single-stranded nucleic acid polymer of the four nucleotides A, C, G, and U joined through a backbone of alternating phosphate and ribose sugar residues. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Note • Ribose, found in RNA, is a "normal" sugar, with one oxygen atom attached to each carbon atom. • Deoxyribose, found in DNA, is a modified sugar, lacking one oxygen atom (hence the name "deoxy"). This difference of one oxygen atom is important for the enzymes that recognize DNA and RNA, because it allows these two molecules to be easily distinguished inside organisms. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Note • The 2ʹ-hydroxyl group on the ribose ring is a major cause of instability in RNA, because the presence of alkali leads to rapid cleavage of the phosphodiester bond linking ribose and phosphate groups. In general, this instability is not a significant problem for the cell, because RNA is constantly being synthesized and degraded. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA üMessenger RNA (mRNA) What is mRNA? mRNA delivers the information encoded in one or more genes from the DNA to the ribosome, a specialized structure, or organelle, where that information is decoded into a protein. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA üTransfer RNA (tRNA) tRNA carries individual amino acids into the ribosome for assembly into the growing polypeptide chain. The tRNA molecules contain 70 to 80 nucleotides and fold into a characteristic cloverleaf structure. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA üTransfer RNA (tRNA) Specialized tRNAs exist for each of the 20 amino acids needed for protein synthesis, and in many cases more than one tRNA for each amino acid is present. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA The amino acids are loaded onto the tRNAs by specialized enzymes called aminoacyl tRNA synthetases, usually with one synthetase for each amino acid. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA üRibosomal RNA (rRNA) What is rRNA? Ribosomal RNA (rRNA) molecules are the structural components of the ribosome. The rRNAs form extensive secondary structures and play an active role in recognizing conserved portions of mRNAs and tRNAs. They also assist with the catalysis of protein synthesis. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA üRibozymes Ribozymes (ribonucleic acid enzymes) are RNA molecules that are capable of catalyzing specific biochemical reactions, similar to the action of protein enzymes. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA üAntisense RNAs Most antisense RNAs are synthetically modified derivatives of RNA or DNA with potential therapeutic value. In nature, antisense RNAs contain sequences that are the complement of the normal coding sequences found in mRNAs (also called sense RNAs). INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA üAntisense RNAs Like mRNAs, antisense RNAs are single-stranded, but they cannot be translated into protein. They can inactivate their complementary mRNA by forming a double-stranded structure that blocks the translation of the base sequence. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA üAntisense RNAs Artificially introducing antisense RNAs into cells selectively inactivates genes by interfering with normal RNA metabolism. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Types of RNA üViral genomes Many viruses use RNA for their genetic material. Some common examples include poliovirus, human immunodeficiency virus (HIV), and influenza virus, all of which affect humans, and tobacco mosaic virus, which infects plants. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism The three main processes of DNA metabolism are; qReplication qRecombination qRepair These processes are carried out by specialized machinery within the cell. DNA must be replicated accurately in order to ensure the integrity of the genetic code. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Errors that creep in during replication or because of damage after replication must be repaired. Recombination between genomes is an important mechanism to provide variation within a species and to assist the repair of damaged DNA. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication DNA replication is a semiconservative process in which the two strands are separated and new complementary strands are generated independently, resulting in two exact copies of the original DNA molecule. Each copy thus contains one strand that is derived from the parent and one newly synthesized strand. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Prior to DNA replication, the chromatin loosens giving cell replication machinery access to the DNA strands. The replication process essentially takes place in four steps. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 1: Replication Fork Formation Before DNA can be replicated, the double stranded molecule must unwind and then be “unzipped” into two single strands. In order to unwind DNA, these interactions between base pairs must be broken. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 1: Replication Fork Formation This is performed by an enzyme known as DNA helicase. DNA helicase disrupts the hydrogen bonding between base pairs to separate the strands into a Y shape known as the replication fork. This area will be the template for replication to begin. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 Metabolism DNA Replication Step 1: Replication Fork Formation What keeps the fork open and prevents super coiling? 1. SSB: Single stranded binding proteins 2. Topoisomerase INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 1: Replication Fork Formation Recall : The polynucleotide runs from 5’to 3’ This directionality is important for replication as it only progresses in the 5' to 3' direction. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 1: Replication Fork Formation However, the replication fork is bi-directional; one strand is oriented in the 3' to 5' direction while the other is oriented 5' to 3’. The two sides are therefore replicated with two different processes to accommodate the directional difference. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 2: Primer Binding The leading strand is the simplest to replicate. Once the DNA strands have been separated, a short piece of RNA called a primer binds to the 3' end of the strand. The primer always binds as the starting point for replication. Primers are generated by the enzyme DNA primase. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 3: Elongation Enzymes known as DNA polymerases are responsible creating the new strand by a process called elongation. There are five different known types of DNA polymerases in bacteria and human cells. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 3: Elongation Replication proceeds in the 5' to 3' direction on the leading strand, this newly formed strand is continuous. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 3: Elongation The lagging strand begins replication by binding with multiple primers. Each primer is only several bases apart. DNA polymerase then adds pieces of DNA, called Okazaki fragments, to the strand between primers. This process of replication is discontinuous as the newly created fragments are disjointed. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 4: Termination Once both the continuous and discontinuous strands are formed, DNA Pol I (exonuclease) removes all RNA primers from the original strands. These primers are then replaced with appropriate bases. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 4: Termination DNA Pol III (exonuclease) “proofreads” the newly formed DNA to check, remove and replace any errors. Another enzyme called DNA ligase joins the Okazaki fragments together forming a single unified strand INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 4: Termination The ends of the linear DNA present a problem as DNA polymerase can only add nucleotides in the 5ʹ to 3ʹ direction. The ends of the parent strands consist of repeated DNA sequences called telomeres. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 4: Termination The ends of the linear DNA present a problem as DNA polymerase can only add nucleotides in the 5ʹ to 3ʹ direction. The ends of the parent strands consist of repeated DNA sequences called telomeres. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 4: Termination Telomeres act as protective caps at the end of chromosomes to prevent nearby chromosomes from fusing. A special type of DNA polymerase enzyme called telomerase catalyzes the synthesis of telomere sequences at the ends of the DNA. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Replication Step 4: Termination Once completed, the parent strand and its complementary DNA strand coils into the familiar double helix shape. In the end, replication produces two DNA molecules, each with one strand from the parent molecule and one new strand. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Replication-Enzymes review • DNA helicase Unwinds and separates double stranded DNA as it moves along the DNA. It forms the replication fork by breaking hydrogen bonds between nucleotide pairs in DNA. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Replication-Enzymes review • DNA primase A type of RNA polymerase that generates RNA primers. Primers are short RNA molecules that act as templates for the starting point of DNA replication. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism • DNA polymerases Synthesize new DNA molecules by adding nucleotides to leading and lagging DNA strands. (Proof reads & repairs) INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism Topoisomerase or DNA Gyrase Unwinds and rewinds DNA strands to prevent the DNA from becoming tangled or supercoiled. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 DNA Metabolism • DNA ligase Joins DNA fragments together by forming phosphodiester bonds between nucleotides. INTRODUCTION TO BIOMEDICAL ENGINEERING BMNG 1210 ANY QUESTIONS? ‘But because of his great love for us, God, who is rich in mercy, made us alive with Christ even when we were dead in transgressions—it is by grace you have been saved. EPHESIANS 2:4-5
0
advertisement
Related documents
Download
advertisement
Add this document to collection(s)
You can add this document to your study collection(s)
Sign in Available only to authorized usersAdd this document to saved
You can add this document to your saved list
Sign in Available only to authorized users