Compendium 12 Notes PDF

Compendium 12 Notes Lecture 1 Nucleic acids - First discovered in the nuclei of cells, found in all cells - Organic macromolecules (C,H,O,N,P) main information carrying molecules which direct the process of protein synthesis and determine the hereditary characteristics of an individu...

Compendium 12 Notes Lecture 1 Nucleic acids - First discovered in the nuclei of cells, found in all cells - Organic macromolecules (C,H,O,N,P) main information carrying molecules which direct the process of protein synthesis and determine the hereditary characteristics of an individual - Polynucleotides/polynucleotide chain -- a chain of repeating monomers called nucleotides - Nucleotides - A pentose sugars -- deoxyribose, ribose - A phosphate group - A nitrogenous base -- adenine, guanine, cytosine, thymine, uracil - Nucleoside = pentose sugar + nitrogenous base - Nucleotide = nucleoside + phosphate group - Sequence of nitrogenous bases caries the information - Two major classes -- deoxyribonucleic acid (DNA), Ribonucleic acid (RNA) DNA - DNA = deoxyribonucleic acid - Mainly found in the nucleus but also in the mitochondria - Contributes to the blueprint that codes for protein synthesis - Approximately 20 000 to 25 000 genes in the human genome - Only 1.5% of DNA is due to genes - 98.5% of DNA is non-coding -- regulatory sequences, introns, and non coding DNA -- e.g. repeat elements Structure of DNA - Double helix molecule (Watson and Crick 1953) - Double stranded polymer -- two nucleotide chains, antiparallel - Alternating sugar phosphate backbone - Pentose sugar -- deoxyribose - Complimentary nitrogenous bases from rungs of the ladder - Adenine -- thymine - Guanine -- cytosine - Nitrogenous bases are held together by very weak hydrogen bonds Organisation of DNA - Double strands of DNA in a twisted ladder - DNA is wrapped around proteins called histones - DNA and histones bundled together is called chromatin - Chromatin twists and condenses to form chromosomes - Each chromosome contains hundreds to thousands of genes Quantity of DNA - Each somatic human cell nucleus has 2 copies of each chromosome, one is inherited from the mother and one from the father - Somatic cells with 46 chromosomes (23 pairs) are said to have the full amount of DNA -- diploid - The maternal and paternal chromosomes of a pair are called homologous chromosomes (make a homologous pair) - Gametes (sperm and egg) only have one chromosome of each of each homologous pair (have 23 chromosomes), have half the normal amount of DNA (haploid) - Humans have 22 pairs of autosomal chromosomes and 1 pair of sex chromosomes - Women have 2x X chromosomes and men have one X and one Y - When cells are dividing, the chromatin condenses to form chromosomes and is easier to see and can be arranged next to their pair -- this kind of map is called a karyotype Karyotype - A map of chromosomes in a dividing cell - Male karyotype (22 autosomes + XY) - On each chromosome there are segments represented by colours, these segments represent a gene which controls the production of a protein - There are many genes coding for many different proteins on each chromosome - When comparing a homologous pair they will both have genes for the same thing which could code differently, in this case the dominant gene will be displayed - The two different genes are referred to as alleles RNA - RNA = ribonucleic acid - Single stranded polymer, self-complimentary sequences which forms folds, bulges and helices - Supports DNA during protein synthesis - Found in both the nucleus and the cytoplasm - Alternating sugar phosphate backbone - Pentose sugar -- ribose - Nitrogenous bases - Adenine -- uracil - Guanine -- cytosine - 3 types -- mRNA(messenger), tRNA(transfer), rRNA(ribosomal) - Different relative sizes, shapes and roles to play in protein synthesis - Messenger RNA carries the information from the DNA to the ribosome through the process of transcription - Transfer RNA brings the amino acids to the ribosome for production of proteins in translation - Ribosomal RNA the integral part of the ribosomes Terminology - Genetics: the study of heredity, where you look at the DNA, the chromosome and how the genes are expressed, how different genes express differently - Gene: segment of DNA that codes for a protein - Allele: alternative form of a gene - Genotype: the actual gene (AA, Aa, aa) - Phenotype: the persons appearance (blue eyes, brown hair) - Dominant and recessive alleles: any allele that is able to express its self in a single dose is a dominant allele but if it requires 2 doses of that allele for it to be expressed it is recessive - Sex linked traits: traits effected by genes on the sex chromosomes Lecture 2 Proteins - The most diverse biomolecules in the human body - Important macromolecules, at least 10 000 in our body - Contain carbon, hydrogen, oxygen and nitrogen bound by covalent bonds, may contain sulphur, phosphorus, iron and iodine - Long chain of amino acids (aa), linked to each other by peptide bonds - Made from 20 amino acids, each amino acid has specific properties due to its side chains (part of the amino acid not involved in linking to each other) - Essential amino acids (can't be synthesised in the body so must be consumed in the diet) (9), non-essential aa (can be synthesised in the body from raw material) (5), conditional aa (not normally essential but can be required in times of illness or stress) (6) - Each amino acid has an amine group, a carboxyl group, a hydrogen atom and a side chain (R) - Some of the side chains are non-polar and hydrophobic (water fearing) while others are hydrophilic (water loving), or positively or negatively charged - Dipeptide -- 2 aa - Oligopeptide -- 3-10 aa - Polypeptide -- 10 or more aa - Protein -- 50 or more aa Functions of proteins +-----------------------------------+-----------------------------------+ | Role | Example | +===================================+===================================+ | Regulation | Enzymes control chemical | | | reactions. Hormones regulate many | | | physiological processes. For | | | example insulin effects glucose | | | absorption into cells | +-----------------------------------+-----------------------------------+ | Transport | Haemoglobin transports oxygen and | | | carbon dioxide in the blood. | | | Plasma proteins transport many | | | substances in the blood. Proteins | | | in plasma membranes control the | | | movement of materials into and | | | out of the cell | +-----------------------------------+-----------------------------------+ | Protection | Antibodies protect against | | | microorganisms and other foreign | | | substances | +-----------------------------------+-----------------------------------+ | Contraction | Actin and myosin in the muscle | | | are responsible for muscle | | | contraction. | | | | | | Flagella allows movement and so | | | do cilia | +-----------------------------------+-----------------------------------+ | Structure | Collagen fibres from a structural | | | framework in many parts of the | | | body. Keratin adds strength to | | | skin, hair and nails | +-----------------------------------+-----------------------------------+ | Energy | Proteins can be broken down for | | | energy, per unit of weight, they | | | yield as much energy as | | | carbohydrates do | +-----------------------------------+-----------------------------------+ | Communication | Cell to cell communication by | | | protein receptors on the cell | | | membrane and neurotransmitters | | | are also made up of proteins | +-----------------------------------+-----------------------------------+ - Recommended protein intake is 10-35% of total calories Protein structure - Interactions between side groups in a long chain, and the peptide bonds, affect the way a protein can fold and take shape - Primary - Sequence of amino acids linked by peptide bonds - Secondary - Protein folds to form secondary structures because the amino acids have different side chains - Two regular folding patterns: alpha helices (keratin) and beta pleated sheets (fibroin, silk) - Tertiary - The 3D shape is determined by the folding of the secondary structure, the a-helices and b-sheets fold to form unique structures which are held together by the bonds between amino acids that may be far apart in the actual polypeptide chain - Quaternary - Combined three-dimensional structure of two or more polypeptide chains - E.g., haemoglobin which consists of 2 alpha and 2 beta chains Types of proteins - Fibrous - Simple elongated polypeptide chains arranged in parallel fashion along a single axis - Are usually insoluble in water and stable - Provide mechanical support and tensile strength, more structural - Are abundant outside of the cell where they make up a lot of matrix in between cells - Less sensitive to changes in temperature, pH, ect. - E.g. collagen, keratin, myosin, elastin, actin - Globular - Polypeptide chain folds up into a compact shape, like a ball with a rough surface - Usually, water soluble - Mobile, chemically active - Play critical roles in nearly all biological processes, more functional - Sensitive to changes in temperature, pH, ect. - E.g., haemoglobin, myoglobin, insulin, most enzymes, antibodies - Membrane proteins - Histones and glucose transporters Lecture 3 The Proteome - The proteome of a cell is all the proteins that a cell makes and proteomics is the study of the proteins in a cell - All cells don't make all proteins. The proteome of a cell can be compared to another to see how they are different - Even though all cells are derived from the same parent cell so have the same DNA they produce different things by switching genes on or off - A muscle cell vs a skin cell - A melanoma vs a normal melanocyte - Cells are protein factories that constantly synthesise many different proteins - These proteins are used for cell functions or they can be exported - Intracellular use of extracellular use - The cell's DNA contains all the cell needs to make proteins Protein synthesis -- basic concept - The specific arrangement of amino acids determines the shape, properties and functions of a protein - Gene: a segment of DNA, that specifies the structure of a protein (there are various genes on a strand of DNA) - Genetic code: specific arrangement of nucleotides in DNA and RNA that determine the amino acid sequence of a particular protein - Gene expression: production of proteins form the information stored in DNA - Central dogma: a directional flow of information from DNA -\> RNA -\> protein - Gene expression involves two steps - Transcription - Occurs in the nucleus - A copy of a small part of the stored information in DNA (gene) is produced - DNA -\> mRNA - Translation - Occurs in the cytoplasm - The copied information is converted into a protein - mRNA -\> protein Transcription - transcription factors recruit the enzyme RNA polymerase which polymerises messenger RNA - polymerisation: two molecules combine to form a larger molecule - double helix structure - sugar-phosphate backbone - 2 polynucleotide chains - Nitrogenous bases - The two strands are complimentary through base pairing - One of the strands is the coding strand (contains the gene sequence) and the other is the template strand - The template strand is used to produce RNA 1. DNA uncoils/unzips separating 2. RNA polymerase -\> messenger RNA (mRNA) -- RNA polymerase attaches to the promoter region and starts synthesising messenger RNA by reading the nitrogenous bases and brings in the complimentary nitrogenous base or nucleotide with a complimentary nitrogenous base - Adenine pairs with Thymine - Guanine pairs with cytosine - In RNA thymine is replaced by uracil - The process continues till a the terminator region is reached - There are special signals/sequences in DNA which indicate where a gene starts and stops 3. mRNA exits the nucleus through a nuclear pore to the cytoplasm Translation - the mRNA finds a ribosome for protein synthesis, either bound to the rough endoplasmic reticulum or free in the cytoplasm - the ribosome can only read 3 nitrogenous bases (one codon) at a time and pairs those with their corresponding transfer RNA molecule by bringing them to the site - the transfer RNA has 2 binding sites - one with a set of 3 nitrogenous bases (anticodon) - one for a corresponding amino acid - as the ribosome continues moving along the mRNA reading bases it the amino acids bind together through peptide bonds and the tRNA detaches from its amino acid and returns to the cytoplasm to pick up the specific amino acid and get ready for the next process in case it is required again - polyribosome context: once one ribosome has moved down the mRNA a little, another ribosome can attach to the same mRNA and this can happen with multiple ribosomes so that it can make multiple copies of the protein - once the stop codon is reached, the polynucleotide chain is released codons and amino acids - there are 64 possible codons in mRNA and only 20 are naturally occurring amino acids - information carried in the mRNA is called the genetic code and a codon represents a specific amino acid during translation - there are 4 nitrogenous bases - Adenine - Guanine - Cytosine - Uracil - some amino acids are specified by only one codon - e.g, methionine, also the start codon (AUG) hence all chains start with methionine - others are specified by up to 6 different codons - e.g. Leucine (UUA, UUG, CUU, CUC, CUG, CUA) - DNA code is 'degenerate' meaning several code words have the same meaning - Three codons do not code for an amino acid but the termination of of the peptide chain - Stop codons -- UAG, UAA, UGA Translation summary - mRNa carries genetic information from the nucleus to the ribosomes - the sequence is read by the translational machinery in the ribosomes, in lots of 3 nucleotide (nucleotide triplets = codon) - translation starts at the start codon (AUG) of each gene in the mRNA - each codon codes for a specific amino acid - as each codon is read, a tRNA with a specific complimentary sequrnce (anticodon) binds to the triplet - the tRNA carries the amino acid specified by the codon - amino acids are joined together by the peptide bonds, in the sequence specified by the mRNA, to make a peptide/protein post translational modification - the chemical modification of a protein following translation - it is one of the last steps in protein synthesis - after translation proteins can be modified by attaching other functional grpups which can change ir extend its functions - e.g lipids (lipoproteins) carbohydrates (glycoproteins) - amino acids may be cleaved of the end of the protein or polypeptide can be cut in half e.g. insulin - other modifications such as phosphorylation are a common way of controlling the behaviour of a protein, for instance activating or inactivating an enzyme - proteins can not be produced in active form because if they are produced in active form they will start digesting the cell in which they are produced - proteins are activated when they reach their destination Lecture 4 Cells - somatic cell: - a biological cell forming the body of a multicellular organism - most cells - 46 chromosomes (diploid number) - Mitosis - E.g. epithelial cells, muscle cells and neurons - germ cell: - cells that give rise to gametes - located in the gonads (ovaries and testes) - diploid -- 46 chromosomes - meiosis - gamete cell: - cells that fuse during sexual reproduction - sperm or egg (spermatocyte or oocyte) - 23 chromosomes (haploid number) Cell life cycle - Cells spend the majority of their life in interphase - Interphase: the phase between cell divisions. Ongoing normal cell activities - E.g. makes hormones, transmits action potentials, and contracts. Replication of DNA and preparation for division - The first phase consists of regular metabolism - The second phase includes DNA replication - The third phase is preparation for the division - Mitosis: a series of events that leads to the production of 2 somatic cells by division of one mother cell into two daughter cells. These cells are genetically identical. - Prophase - metaphase - anaphase - telophase - cytokinesis: division of cell cytoplasm chromosomes and chromatin - chromatin: DNA complexed with proteins (histones) - during cell division, chromatin condenses into pairs of chromatids called chromosomes. Each pair of chromatids is joined by a centromere Chromosomes - humans: - 23 pairs of chromosomes - 46 diploid number - 22 autonomic pairs - One sex determining pair - XX -- female - XY -- male - A karyotype is a map of chromosomes - To get this a cell must be stained and photographed during metaphase - Homologous: pairs of chromosomes -- where one is from the father and one is from the mother (gametes) - Locus: the location of a gene on a chromosome - Allele: different forms of the same gene, the same locus will be found on the other homologous chromosome DNA Replication - Interphase: DNA replication occurs. Each chromosome becomes doubled, consisting of 2 identical strands of DNA - During interphase, the number of chromosomes is not increased but the amount of DNA is - The cell is getting ready to divide Structure of a meiotic chromosome 1. The DNA of a chromosome is dispersed as chromatin 2. The DNA molecule unwinds, and each strand of the molecule is replicated 3. During mitosis, the chromatin from each replicated DNA strand condenses to form a chromatid, the chromatids are joined at the at the centromere to form a single chromosome 4. The chromatids separate to form 2 new, identical chromosomes. The chromosomes will unwind to form chromatin in the nuclei of the two daughter cells Mitosis - Mitosis produces 2 identical daughter cells - Mitosis is happening all the time, during wound healing, skin renewal, ect. - Prophase: chromatin condenses to form chromosomes, centrioles migrate to either end of the cell, spindle fibres attach to centromeres - Metaphase: chromosomes are aligned at the nuclear equator - Anaphase: spindle fibres separate the chromatids, 2 identical sets of chromosomes are moved to separate ends of the cell, cytokinesis begins - Telophase: the nuclear envelope reforms around each set of chromosomes, chromosomes decondense into chromatin, cytokinesis continues - Cytokinesis: cytoplasmic division Centrioles and spindle fibres - 2 centrioles located in the centrosome - Centre of microtubule (spindle fibre) formation - Before cell division, centrioles divide and move to either end of the cel and organise spindle fibres Mitosis -- IPMAT - Can be remembered by "I Pay My Annual Taxes" - Interphase is th time between cell divisions. DNA is present as thin threads of chromatin in the nucleus. DNA replication occurs during the 'S' phase of interphase and organelles other than the nucleus and centrioles duplicate during interphase - In prophase the chromatin condenses into chromosomes. Each chromosome consists of two chromatids joined at the centromere. The centrioles move to opposite ends of the cell, and the nucleus and the nuclear envelope disappear. Microtubules form near the centrioles and project in all directions, some of the microtubules end blindly and are called astral fibres. Others, known as spindle fibres, project towards an invisible line known as the equator and overlap with fibres from the opposite side - In metaphase the chromosomes align in the center of the cell in association with the spindle fibres. Some spindle fibres are attached to kinetochores in the centromere of each chromosome - In anaphase, the chromatids separate, and each chromatid is then refered to as a chromosome. Thus when the centromeres divide, the chromosome number is double and there are two identical sets of chromosomes. The chromosomes assisted y the spindle fibres move towards the centrioles at each end of the cell. Separation of the chromatids signals to the beginning of anaphase, and by the time anaphase has ended, the chromatids have reached the poles of the cell. Cytokenuisis begins during anaphase and cleavage furrow forms around the cell - In telophase, migration of each set of chromosomes is complete, the chromosomes unravel to form chromatin threads, the nuclear envelope forms and cytokinesis continues to form two cells - Mitosis is complete and a new interphase begins. The chromosomes have unravelled to form chromatin, cell division has produced two daughter cells each with DNA which is identical to the parent cell's DNA Mitosis example - Skin -- keratinised stratified squamous epithelium - Constantly regenerating from the basal layer - High abrasion; skin, gastrointestinal tract -- oral cavity and anus, female reproductive system -- cervix and vagina - Normal growth: in utero (pregnancy), puberty. Wound healing, red blood cells, mitosis inhibitors used in cancer treatment -- stop tumour growth - Brain, heart, skeletal muscle -- slow growth Meiosis - Germ cells divide and produce gametes - Specialised for sexual reproduction - DNA replication followed by 2 cell divisions - Produces 4 genetically different daughter cells - Gametes are haploid - Only one homolog from each homologous pair - Resulting gametes (egg/sperm) unite to form a zygote -- a new genetically unique human being - The process: 1. Early prophase 1: the duplicated chromosomes become viable chromatids 2. Middle prophase 2: homologus choromsomes synapse to form tetrads. crossing over may occur at this stage (where homologus pairs of chromosomes come together and form tetrads, the process is called synapsis, the chromasomes swap a bit of DNA) 3. Metaphase 1: homologous chromosomes align at the center of the cell and random assortment (which chromosome ends up on which side is random) of homologous chromosomes occurs 4. Anaphase 1: homologous chromosomes move apart to opposite sides of the cell 5. Telophase 1: new nuclei form and the cell divides 6. Prophase 2: there is no DNa replication before the start of meiosis 2, it starts with two non identical cells both with 23 chomosomes and the DNA is replicated 7. Metaphase 2: chromosomes align along the center of the cell 8. Anaphase 2: chromatids separate and each is now called a chromosome 9. Telophase 2: new nuclei form around the chromosomes. Cells divide to form 4 daughter gamete cells with a haploid number of chomosomes (n) Homologous crossing over - Prophase 1: homologous chromosomes line up next to each other. DNA is exchanged between the adjacent homologous chromatids. Sister chromatid strands of each chromosome are no longer identical resulting in an exchange of genetic material between mother and father chromosomes - This causes new gene combinations and genetic variation Spermatogenesis - Meiosis occurring in the gonads - 4 functional sperm cells per division - Non identical with 23 chromosomes - Lifelong process in the testes Oogenesis - The ovaries make gametes (oocytes) via meiosis - At birth the ovaries contain all the oocytes they will ever have -- stalled in prophase 1 - 1 functional oocyte per division - 3 polar bodies produced - Non identical with 23 chromasomes Tutorial 2\. the difference between a protein, peptide and polypeptide is that a protein is made up of more than 50 amino acids, a polypeptide is made up of 10-50 amino acids and a peptide is 2 or more 3\. DNA codes for proteins +-----------------------------------+-----------------------------------+ | DNA | RNA | +===================================+===================================+ | 2 strands (template and coding) | 1 strand | | | | | Double helix shaped molecule | One long strand maybe folded | | | structure | +-----------------------------------+-----------------------------------+ | Deoxyribose | Ribose | +-----------------------------------+-----------------------------------+ | Thymine, guanine, cytosine, | Guanine, cytosine, adenine, | | adenine | uracil | +-----------------------------------+-----------------------------------+ | longer | Shorter | +-----------------------------------+-----------------------------------+ 2\. mRNA is made in the nucleus through the process of transcription 3\. 3 amino acid base codes code for one amino acid 4. mRNA Carries codes from the DNA in the nucleus to the ribosomes for protein synthesis ------ ----------------------------------------------------------------------------------------------------- tRNA Connects anticodons to the mRNA and ensures the correct amino acids are joined in the correct order rRNA Joins the amino acids together during translation with peptide bonds 5\. The start codon is AUG, methionine, all proteins start with this 6. DNA **coding** strand CTG ACT CCT GAG GAG AAG ------------------------- --------- ----------- --------- --------------- --------------- -------- DNA **template** strand GAC TGA GGA CTC CTC TTC mRNA CUG ACU CCU GAG GAG AAG Amino acid Leucine Threonine proline Glutamic acid Glutamic acid Lysine 7\. genes turn on and off so that a cell can specialise to their function +-----------------------------------+-----------------------------------+ | Interphase | Normal metabolic activities (90% | | | of the time) | +===================================+===================================+ | Mitosis | Prophase: chromatids condense to | | | be chromosomes, Cell membrane | | | starts to disappear, centrioles | | | move to either side of the cell | | | and spindle fibres form | | | | | | Metaphase: the chromosomes line | | | up at the equator and the spindle | | | fibres attach at the centromere | | | | | | Anaphase: sister chromatids are | | | pulled apart | | | | | | Telophase: chromosomes unravel | | | and become chromatins again and | | | the nuclear envelope starts to | | | form, microtubules start to | | | disappear | +-----------------------------------+-----------------------------------+ | cytokinesis | Cytoplasm divides forming two | | | identical daughter cells | +-----------------------------------+-----------------------------------+ Mitosis stages interphase Prophase metaphase Anaphase Telophase Mitosis complete ---------------- ------------ ---------- ----------- ---------- ----------- ------------------ Answer A C F D E B 1. To produce the haploid cells (reductional division) 2. For genetic variation within the human population 3. No, they are variable 4. One copy