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Week 1: CH 1 - Intro to biology Biology: the study of life - Some different types of biologists - cell/ molecular biologist - Geneticists - Biochemists - Ecologists - Physiologists - Evolutionary biologists - Bioinformaticians What kinds of properties are un...

Week 1: CH 1 - Intro to biology Biology: the study of life - Some different types of biologists - cell/ molecular biologist - Geneticists - Biochemists - Ecologists - Physiologists - Evolutionary biologists - Bioinformaticians What kinds of properties are unique to life? Some properties The core theme in biology: evolution - Can you define “evolution”? - Darwin said “descent with modification Evolution is central (“nothing in biology makes sense except in the light of evolution” - theodosius dobzhansky) - What makes a strong argument for a particular position? - Evolution explains both the diversity and unity of life - Multiple independent lines of evidence support evolution - Natural selection is one of the main mechanisms of evolution, but is not synonymous with the word evolution Natural selection Darwin observed that - Individuals in a population vary in their traits, many of which are heritable - More offspring are produced than survive, and competition is inevitable - Species generally suit their environment Darwin inferred that - Individuals best suited to their environment are more likely to survive and reproduce - Over time, more individuals in a population will have these advantageous traits Evolution occurs because of the unequal reproductive success of individuals. In other words, the environment “selects” for beneficial traits Peppered moths and the industrial revolution What is important about this example of natural selection? “After the pollution from the industrial revolution started affecting trees, the lighter peppered moths were more susceptible to being eaten than the darker ones. This is because the darker moths had camouflage and lived longer, thus giving them more time to breed. Grouping species: the basic idea Taxonomy - branch of biology that names and classifies species into groups of increasing breadth Phenotype: how something looks Levels of classification There are 8 levels of classification, from lowest to highest is - Species - Genus - Family - Order - Class - Phylum - Kingdom - Domain Ways to memorize this: Donkey Kong Plays Chess Outside For G Sus Darwin and the tree of life “Darwin postulated that life on earth evolved from ancient species that diverged overtime - like tree branches from single trunk” The Three Domains of Life 3 domains - Domain Bacteria and domain Archaea compose the prokaryotes - Most prokaryotes are single - celled and microscopic - Domain Eukary includes all eukaryotic organisms Note: - Prokaryotic organism have prokaryotic cells: cells that don’t have a nucleus - Eukaryotic organism have eukaryotic cells: they do have a membrane bound nucleus Unity in the diversity of life A striking unity underlies the diversity of life; for example - DNA is the universal genetic language common to all organism - Unity is evident in many features of cell structure The architecture of cilia in eukaryotes Exploring: levels of biological organization Figure 1.4 1. The biosphere: the entire portion of earth is inhabited by life; the sum of all the planet’s ecosystem 2. Ecosystems: consists of all living things in a particular area; along with all the non-living components of the environment with which life interacts, such as soil, water, atmospheric gases, and light. 3. Communities: all organisms that inhabit a particular area; an assemblage of populations of different species living close enough together for potential interaction. 4. Population: consists of all the individual of species living within the bounds of a specified area 5. Organisms: individual living things 6. Organs: within an orgam, each tissue has a distinct arrangement and contributes particular properties organ function 7. Tissues: a group of cells that work together, performing a specialized function  8. Cells: is life’s fundamental unit of structure and function. - Some organisms consist of a single cell, which performs all the functions of life. Other organisms are multicellular and feature a division of labour among specialized cells 9. Organelles: any of several membrane enclosed structures with specialized functions; suspended in the cytosol of eukaryotic cells. 10. Molecules: a chemical structure consisting of two or more units called atoms Emergent properties - Emergent properties emerge from the arrangement and interaction of parts within a system - Emergent properties are not unique to life - For example, a box of bike parts is not that useful on its own Terms: Emergent properties: new properties that arise with each step upwards in the hierarchy of life, owing to the arrangement and interaction of parts as complexity increases. Aren’t unique to life Systems biology: an approach to studying biology that aims to model the dynamic behavior of whole biological systems based on a study of the interactions among systme’s parts Structure and function are correlated at all levels of biological organization - For example, a leaf is thin and flat, to maximize capture of sunlight The Cell: an Organism’s Basic Unit of Structure and Function - The cell is the lowest level of organization that can perform all activities are required for life Cell theory: was first developed in the 1800s based on the observations of many scientists. States that all living organism are made of cells, which are basic units of life Forms of cells All cells - Are enclosed by a membrane that regulates the passage of materials between the cell and its surroundings  - Use DNA as their genetic information Two main forms of cells Eukaryotic cells has membrane-enclosed organelles Prokaryotic cell is simpler, usually smaller, no membrane-enclosed organelles Note: all other forms of life, including plants and animals, are composed of eukaryotic cells. Some organelles, such as DNA - containing nucleus, are found in the cells of all eukaryotes; other organelles are specific to particular cell types - The cell is the lowest level of organization that can perform all activities require for life Theme: expression and transmission of genetic information - Chromosomes contain most of a cell’s genetic material as DNA (deoxyribonucleic acid) How science is (often) done - The scientific process includes making observations, forming logical hypothesis, and testing them Forming and testing hypothesis - Observations can lead us to ask question - A hypothesis is a tentative answer to a well-framed question  - A scientific hypothesis leads to predictions that can be tested by observation or experimentation Example of hypothesis-based inquiry Can science be non-hypothesis-driven? Theories in science In the context of science, a theory is - Broader in scope than a hypothesis - General, and can lead to new testable hypotheses - Supported by a larger body of evidence than hypothesis Ch 5: Macromolecules All living things are made up of four classes of large biological molecules; 1. Carbohydrates (energy and building material) 2. Lipids (membranes, hormones, etc.) 3. Proteins (very wide range of functions) 4. Nucleic acids (store and express hereditary info) Macromolecule: a giant molecule formed by the joining of smaller molecules, usually by a dehydration reaction Note: all three, except for lipids, are chain-like molecules called polymers (from the greek-polys, many, and micross, part) Terms: Polymer: a long molecule consisting of many similar or identical building blocks linked by covalent bonds Covalent bond: a type of strong chemical bond in which 2 atoms share one or more pairs of valence electrons Monomers: the subunit that serves as the building block of a polymer. (In addition to forming polymers, some monomers also have other functions of their own.) The Synthesis of Polymers (repeating chain of monomers stuck together) A dehydration reaction occurs when two monomers bond together through the loss of a water molecule - Enzyme catalyzed fractions - When a bond forms between two monomers, each monomer contributes part of the water molecule that’s released during the ration. One monomer provides a hydroxyl group (-OH), while the other provides a hydrogen. This reaction is repeated as monomers are added to the chain one by one, making a polymer (AKA polymerization) Figure 5.2a The Breakdown of polymers - Disassembled into monomers by hydrolysis reactions, (essentially the reverse of a dehydration reaction - The bond between monomers is broken by the addition of a water molecule, with a hydrogen from water attaching to one monomer and the hydroxyl group attaching to the other Figure 5.2b Carbohydrates serve as fuel and building material - The simplest carbohydrates are monosaccharides (monomers), or single sugars - Polysaccharides are polymers composed of many sugar monomers Disaccharides: are double sugars, consisting of two monosaccharides joined by a covalent bond Sugars - Monosaccharides have molecular formulas that are usually multiples of CH₂0 - Glucose (C₆H₁₂0₆) Depending on the location of the carbonyl groups (C=O), a sugar is either an aldose (aldehyde sugar) or a ketose (ketone sugar). Ex: glucose is an aldose; fructose; an isomer of glucose, is a ketose Terms Aldose (aldehyde sugars): carbonyl group at end of carbon skeleton Ketose (ketone sugars): carbonyl group within carbon skeleton Carbonyl group: a functional group categorized by a carbon atom double bonded to an oxygen, found within a larger carbon based molecule Polysaccharides Polysaccharides are macromolecules, polymers with a few hundred to a few thousand monosaccharides joined by glycosidic linkages. - Some polysaccharides serve as storage material, hydrolyzed as needed to provide sugar for cells - Other polysaccharides serve as building material for structures that protect the cell or the whole organism - The architecture and function of a polysaccharide are determined by its sugar monomers and by the positions of its glycosidic linkages Storage polysaccharides - Glycogen is a storage polysaccharide in animals - Glycogen is mainly in liver and muscle cells - Hydrolysis of glycogen release glucose when the demand for energy increases - Starch, a storage polysaccharide of plants, consists entirely of glucose monomers Figure 5.6b Structural polysaccharides - Cellulose is a major component of plant cell walls - Cellulose is a polymer of glucose, but it’s glycosidic linkages differ from those of starch Glycosidic linkage: a covalent bond formed between two monosaccharides by a dehydration reaction - A disaccharide consists of two monosaccharides joined by a glycosidic linkage Figure 5.6c - Cellulose in human food passes through digestive tract as insoluble fibre (and is eliminated with the feces) - Some microbes have enzymes that digest cellulose - Herbivores, from cows to termites, have symbiotic relationships with these microbes - Chitin is found in arthropod exoskeletons - Provides structural support for fungal cell walls Figure 5.8 Lipids are a diverse group of molecules - Lipids are the one class of large biological molecules that does not form polymers - Unifying feature of hydrophobicity (due to non-polar hydrocarbons) - Biologically important lipids include fats, phospholipids, and steroids) Fats Fats are constructed from glycerol “head” and fatty acid “tails”, linked by an ester bond Glycerol: is an alcohol; each of its 3 carbons bears a hydroxyl group Fatty acid: a carboxylic acid with a long carbon chain. Can vary in length and in the # and location of double bonds; 3 fatty acids linked to a glycerol molecule form a fat molecule, aka a triacylglycerol or triglyceride  - Fats separate from water because the water molecules hydrogen bond to one another and exclude the fats Figure 5.9a - Saturated fatty acids do not have double bonds - Solid at room temperature - Mainly from animal sources Figure 5.10a  - Unsaturated fatty acids have one or more double bonds - Liquid at room temperature - Plant fats and fish fats are usually unsaturated Figure 5.10b - Major function of fat is energy storage - Humans and other mammals store their fat in adipose cells - Adipose tissue also cushions vital organs and insulates the body Fats and diet - A diet rich in saturated fats may contribute to cardiovascular disease - Some unsaturated fatty acids are synthesized in the human body, must therefore be supplied through the diet - Called essential fatty acids  - Essential fatty acids include omega-3 fatty acids, which are required for normal growth - May protect against cardiovascular disease Phospholipids: a major part of cell membranes In phospholipids, two fatty acids and a phosphate group are attached to glycerol - The two fatty acid tails are hydrophobic - The phosphate head group is hydrophilic - These molecules are “polar” - Spontaneously form a lipid bilayer Figure 5.11a and b Steroids - Steroids are lipids with a carbon skeleton consisting of four fused rings - Cholesterol is a component in animal cell membranes - Although cholesterol is an essential component of animal cell membranes, high levels in blood may contribute to cardiovascular disease Figure 5.12 Proteins Account for > 50% of the dry mass of most cells Protein functions include Speeding (catalyzing) chemical reactions - enzymes Structural support Storage Transport Cellular communications Movement Defense against foreign substance - antibodies Enzymes - Enzymes are a type of protein that act as catalysts to speed up chemical reactions - Ex: digestive enzymes catalyze the hydrolysis of bonds in food molecules (lipases, proteases, etc.) - Dead give away for an enzyme is the suffix -ase Proteins are polymers of amino acids All proteins are polymers constructed from the same set of 20 amino acid monomers - The bond between amino acids is called a polypeptide bond, so a polymer of amino acids is also called a polypeptide Amino acid monomers - Amino acids have carboxyl and amino groups on their ends - Amino acids differ in their properties due to differing side chains, called R groups Figure 5.1 Nonpolar amino acids Figure 5.14 Polar amino acids Figure 5.14 Electrically charged amino acids Figure 5.14 What do you think will be the behavior of the different groups of amino acids in water? Um Polypeptides (amino acid polymers) - Amino acids are linked by peptide bonds - A polypeptide (protein) is a polymer of amino acids - Highly variable in length… - FMRFamide - hormone used by invertebrates in mating (4 amino acids)  - Titin - mammalian muscle protein (36 000 amino acids) Figure 5.15 Finding primary sequences of proteins - Bioinformatics: “is a subdiscipline of bio and computer science concerned with the acquisition, storage, analysis,and dissemination of biological data, most often, DNA and amino acid sequences.” Protein structure and function A functional protein consists of one or more polypeptides folded precisely into a unique conformation (shape) Figure 5.16  - The sequence of amino acids determines a protein’s 3D structure - Protein structure determines its function Figure 5.17 All proteins share 3 superimposed levels of structure, known as primary, secondary, and tertiary structure. A fourth level, quaternary structure, arise when a protein consists of 2 or more polypeptide chains Protein structure and function Primary structure, the sequence of amino acids, is like the order of letters in a long word determined by inherited genetic information Figure 5.18a Secondary structure results from hydrogen bonds between repeating constituents - Typical secondary structures include: - A-helix - b-pleated sheet Figure 5.18b Tertiary structure is the overall shape (conformation) of a polypeptide, and is determined by interactions between R groups Figure 5.18 Protein Structure and Function: Tertiary Structure Interactions between R groups include hydrogen bonds, ionic bonds, hydrophobic interactions, and van der Waals interactions  Strong covalent bonds called disulfide bridges reinforce the protein’s structure Cysteine amino acid Figure 5.18 Quaternary structure Quaternary structure results when two or more polypeptide chains form one macromolecule Figure 5.18 Example of Quaternary Structure  - Hemoglobin is a globular protein consisting of four polypeptides: two alpha and two beta chains Figure 5.18 Sickle-Cell Disease: A Change in Primary Structure - A change in primary structure can affect a protein’s structure and function - Sickle-cell disease results from an amino acid substitution in hemoglobin Figure 5.19 What determines protein structure? In addition to primary structure, physical and chemical conditions can affect structure Alterations in pH, salt concentration, temperature, or other environmental factors can cause a protein to denature, or unravel ○ Denatured Proteins Are Biologically Inactive Denaturation: the weak chemical bonds and interactions within a protein may be destroyed, causing the protein to unravel and lose its native conformation (shape) Figure 5.20 Protein folding in the cell Folding often requires help: chaperonin proteins Most proteins probably go through several stages on their way to stable structure Many disease such as alzheimer’s, parkinson’s, and mad cow disease (MCD, a prion disease) are associated with misfolded proteins MCD is a “spongiform encephalopathy” Abnormal structure of the prion protein (PrPc, normal prion protein; PrPSc, abnormally shaped prion protein) What do proteins look like? - X ray crystallography can be used to determine a protein’s 3D structure - Useful video: https://www.youtube.com/watch?v=j4HgLf_eJoc What makes one cell type different from another? - They make different proteins: “differential gene expression” Nucleic acids store, transmit, and help express hereditary information - The amino acid sequence of a polypeptide is dictated by the sequence of a gene The roles of nucleic acids There are two types of nucleic acids - Deoxyribonucleic Acid(DNA) - Ribonucleic Acid(RNA) The link between the nucleic acids and proteins: The Central Dogma of Molecular Biology - Francis Crick “The central dogma of molecular biology describes the flow of genetic info in cells from DNA to messenger RNA (mRNA). It states that genes specify the sequence of mRNA molecules which in turn specify the sequence of proteins.” The structure and function of large biological molecules - You are looking at the organization of gene expression in eukaryotic cells. How is it different in a prokaryotic cell? Figure 5.23 The components of nucleic acids - Nucleic acids are polymers called polynucleotides - Each polynucleotides is made of monomers called nucleotides Figure 5.24a  - Nucleoside = nitrogenous base + sugar - Nucleotide = nucleoside + phosphate group Figure 5.24b There are two types of bases: - Pyrimidines (cytosine, thymine, uracil) have a single six membered ring - Purines (adenine, guanine) have six membered ring fused to a five membered ring - DNA has A, C, T, and G - RNA has A, C, U, and G Figure 5.24c  - In DNA, the sugar is deoxyribose - In RNA, the sugar is ribose Figure 5.24c2 Nucleotide polymers Adjacent nucleotides are joined by covalent bonds formed between - OH group on 3’ carbon of one nucleotide and phosphate on 5’ carbon on next Links create sugar-phosphate backbone with nitrogenous bases as appendages Sequence of bases in a DNA or mRNA polymer is unique for each gene DNA DNA molecules have two polynucleotides spiraling around an imaginary axis, forming a double helix In DNA double helix, two backbones run in opposite 5’→ 3’ directions from each other, an arrangement referred to as antiparallel One DNA molecule includes many genes Figure 5.25a1  DNA bases in opposite strands pair by hydrogen bonding: adenine (A) always with thymine (T), and guanine (G) always with cytosine (C) (“complementary base pairing”) Figure 5.25a RNA RNA molecules are usually single-stranded Complementary pairing can occur between two RNA molecules or within same molecule In RNA, thymine is replaced by uracil (U) so A and U pair Figure 5.25b Genes provide the instructions for the sequence of a protein Cracking the code: codon tables Example: If you had the following sequence of mRNA, what would be the corresponding primary structure of the protein (use single letter amino acid abbreviations)?  AAC GAA GCG CUA N E A L CH 6: The Cell Important tools to study cells - Microscopes - blenders/centrifuges Microscopy Three important parameters of microscopy Magnification- ratio of an object’s image size to its real size Resolution- measure of clarity of the image, distance between points Contrast, visible differences in parts of the sample The size range of cells Figure 6.2 Light microscopy Cells often need to be stained to see them Electron microscopy example: scanning electron microscopy - 3D imaging of surface of tracheal cilia Figure 6.3m Function: to move water relative to the cell in a regular movement of the cilia.This process can either result in the cell moving through the water, typical for many single-celled organisms, or in moving water and its contents across the surface of the cell. Electron Microscopy Example: Transmission Electron Microscopy Profile Fatin Section Of Cilia Specimen Figure 6.3n Cell Fractionation: blending and spinning In cell fractionation cells are broken open, and separated into component parts Centrifuges are used to separate organelles from one another by gradually increasing the centrifugation speed Figure 6.4 Cell Fractionation Functions of organelles can be studied once they are isolated from other components Prokaryotic and Eukaryotic Cells Basic features of all cells Plasma Membrane Semifluid Substance Called Cytosol Chromosomes(carry genes)  Ribosomes (makes proteins) Prokaryotic cells - No nucleus - DNA in an unbound region called the nucleoid - No membrane-bound organelles - Cytoplasm bound by plasma membrane Eukaryotic Cells - DNA in a nucleus bounded by membranous nuclear envelope Membrane-bound organelles - Cytoplasm Between Plasma Membrane And Nucleus - Eukaryotic cells are generally much larger than prokaryotic cells Plasma membrane a selective barrier Allows passage of oxygen, nutrients, and waste General structure of a biological membrane is a phospholipid bilayer Animal Cells Eukaryotic cells have internal membranes that partition the cell into organelles Figure 6.8 Plant Cells Plant and animal cells have mostly the same organelles Unique plant cell structures: Chloroplasts Large Central Vacuoles Cell Walls Plasmodesmata Figure 6.8e The Nucleus The nucleus contains most of the cell’s genes, and is usually most conspicuous organelle Nuclear envelope encloses nucleus Figure 6.9a The Nucleus Pores regulate entry and exit of molecules from nucleus Shape of the nucleus is maintained by nuclear lamina composed of protein Figure 6.9 - DNA and proteins of chromosomes are together called chromatin - Nucleolus within nucleus is the site of ribosomal RNA (rRNA) synthesis Ribosomes: Protein Factories Ribosomes are particles made of ribosomal RNA and protein Ribosomes carry out protein synthesis in two different locations: In The Cytosol (free cytosolic ribosomes) On The Surface Of The endoplasmic reticulum (ER-bound ribosomes) Figure 6.10a Components of endomembrane system - Nuclear Envelope - Endoplasmic Reticulum(ER) - Golgi Apparatus - Lysosomes - Vacuoles - Plasma Membrane - These components are either continuous, or are connected indirectly via vesicles The Endoplasmic Reticulum (ER): Biosynthetic Factory - ER accounts for more than half of total membrane in many eukaryotic cells - The ER membrane is continuous with the nuclear envelope Figure 6.11a Two distinct structural regions of ER - SmoothER, which lacks ribosomes - RoughER, surface is studded with ribosomes Figure 6.11b Functions of Smooth ER The smooth ER - Synthesizes Lipids - Metabolizes Carbohydrates - Detoxifies Drugs And Poisons Stores Calcium Ions The smooth ER and Chronic Alcohol Abuse Functions of Rough ER The rough ER synthesize glycoproteins (proteins modified with covalently linked carbohydrates) Site for synthesis of proteins to be secreted from the cell Produces Transport Vesicles, which distribute lipids and proteins to other components of the endomembrane system The ER is a “membrane factory” for the cell The rough ER stress response Clogged up proteins in the ER due to incomplete/incorrect protein folding Accumulation of misfolded/unfolded proteins poses a cytotoxic risk to the cell Halts translation Two modes of dealing with rER stress Short-term: Increased synthesis of factors that help fold proteins (e.g., chaperone proteins) and slow down translation Long-term: Kill the cell to minimize damage The Golgi Apparatus: Shipping and Receiving Centre Golgi apparatus consists of flattened membranous sacs called cisternae The Golgi Apparatus Golgi apparatus functions Modifies products of the IR Manufacture Certain Macromolecules Sorts And Packages Materials Into Transport Vesicles Lysosomes: Digestive Compartments Lysosome is a membrane-bound compartment of hydrolytic enzymes that can digest macromolecules Lysosomes are very acidic environments, but contain protein enzymes. Do you see a problem here? Lysosomes Some cells can engulf another cell by phagocytosis; forming a food vacuole Figure 6.13a Also recycle the cell’s own organelles and macromolecules through autophagy Figure 6.13b Vacuoles Vacuoles are components of the endomembrane system (derived from ER and Golgi) that perform different functions depending on cell type Food Vacuoles Are Formed By Phagocytosis Contractile Vacuoles,found in many freshwater protists, pump excess water out of cells Central Vacuoles, found in many mature plant cells, hold organic compounds and water Plant cells generally have one large central vacuole, that occupies the majority of the cell’s volume Figure 6.14 Mitochondria and Chloroplasts Change Energy from one Form to Another Mitochondria are the site of cellular respiration, a metabolic process that uses oxygen to generate ATP Chloroplasts, found in plants and algae, are the site of photosynthesis, converting sunlight into sugars The Evolutionary Origins of Mitochondria and Chloroplasts derived from prokaryotes Endosymbiotic Theory Mitochondria and chloroplasts resemble bacteria in numerous ways Contain Free Ribosomes Grow and reproduce independently in cells using prokaryotic-like mechanisms Contain Their Own Genome Endosymbiotic Theory Early ancestor of eukaryotes engulfed an oxygen-using non- photosynthetic prokaryote, evolved into mitochondria A second endosymbiotic event involved a photosynthetic prokaryote being engulfed by a eukaryote containing mitochondria This Endosymbiont Evolved Into A Chloroplast Mitochondria Have a smooth outer membrane and an inner membrane folded into cristae Figure 6.17 Mitochondria are in nearly all eukaryotic cells More on reactions in the cellular respiration chapter! Chloroplasts: Capture of Light Energy Chloroplasts contain the green pigment chlorophyll and enzymes that permit photosynthesis Found in leaves and other green organs of plants and in algae The Cytoskeleton The cytoskeleton is a network of fibres extending throughout cytoplasm It organizes the cell’s structure Figure 6.20 Cytoskeleton Organizes Structures and Activities in Cells The cytoskeleton is composed of three types of structures Microtubules Microfilaments Intermediate Filaments Roles of the Cytoskeleton: Support and Motility Cytoskeleton interacts with motor proteins to produce movement Inside the cell, vesicles can travel along cytoskeleton “highways” Figure 6.21 Microtubules Table 6.1a Microtubules Are Hollow Rods Made Of Proteins Called Tubulin Functions: Shaping the cell Guiding movement of organelles Separating chromosomes during cell division Microtubules and Centrosomes Important microtubule function is chromosome separation during cell division In many cells (including animals), microtubules grow out from a centrosome (“microtubule-organizing centre”) near the nucleus Cilia and Flagella Microtubules control the beating of cilia and flagella, locomotor appendages of some cells Cilia and flagella differ in their beating patterns Figure 6.23 Cilia and Flagella have a similar structure Animation: Cilia and Flagella Right-click slide / select “Play” Microfilaments Table 6.1b Microfilaments are solid rods built as a twisted double chain of actin subunits  Structural role is to bear tension, resisting pulling forces within cell Microfilaments (Actin Filaments) Microfilaments that function in cellular motility contain the protein myosin in addition to actin In muscle cells, thousands of actin filaments are arranged parallel to one another Intermediate Filaments Table 6.1c larger than microfilaments but smaller than microtubules Composed of different proteins, including keratin Support cell shape and fix organelles in place The Extracellular Matrix (ECM) of Animal Cells Animal cells lack cell walls but have an elaborate extracellular matrix (ECM) Functions of the ECM Support Adhesion Movement Regulation The ECM of Animal Cells Made of glycoproteins such as collagen, proteoglycans, and fibronectin bind to receptor proteins in plasma membrane called integrins integrins are “transmembrane proteins” Ch. 7: Membranes - Phospholipids are the most abundant lipid in the plasma membrane Phospholipids are amphipathic molecules, containing hydrophobic and hydrophilic regions - Membranes also contain proteins Fluid Mosaic model Fluid mosaic model: a membrane is a fluid structure with a “mosaic” of proteins embedded in it Testing the fluid mosaic model Cholesterol and membrane fluidity The steroid cholesterol has different effects on membrane fluidity at different temperatures At warm temperatures, it limits movement of phospholipids, preventing the membrane from becoming too fluid At cool temperatures, it maintains fluidity by preventing tight packing Figure 7.5b Membrane Proteins and Their Functions Peripheral proteins are bound to the surface of the membrane Integral proteins penetrate the hydrophobic core, and are embedded in the membrane Integral proteins that span the membrane are called transmembrane proteins Aquaporins: Water channels Is it possible to roughly predict how a membrane protein is laid out across the membrane? If so, how? Bioinformatics and Hydropathy plots Aquaporins (AQPs): are a family of membrane water channels that basically function as regulators of intracellular and intercellular water flow.... AQP facilitates osmotic water transport across plasma membranes and thus transcellular fluid movement. The passive diffusion of one substance across a membrane Figure 7.10a Passive transport - Substances diffuse down their concentration gradient - Requires no energy Effects of Osmosis on Water Balance Osmosis is the diffusion of water across a selectively permeable membrane Water diffuses across a membrane from the region of lower solute concentration to the region of higher solute concentration until the solute concentration is equal Figure 7.11 Water Balance of Cells Isotonic solution: solute concentration is the same as that inside the cell; no net water movement across the plasma membrane Hypertonic solution: solute concentration is greater than that inside the cell; cell loses water Hypotonic solution: solute concentration is less than that inside the cell; cell gains water Water Balance of Cells Figure 7.12 Active Transport Active transport moves substances against their concentration gradients Active transport requires energy, usually in the form of ATP Active transport is performed by specific proteins embedded in membranes e.g. Na+/K+ pump Ch. 8 Metabolism ​ - Metabolism is the total chemical reactions undertaken in a cell ​ - Catabolic vs. anabolic reactions ​ - The cell extracts energy stored in sugars and other energy- containing organic molecules, and applies energy to perform work Organization of the Chemistry of Life into Metabolic Pathways Metabolic pathways begin with a specific molecule (substrate or reactant) and end with a product Each step is catalyzed by a specific enzyme Figure 8.1 Forms of Energy - Energy is the capacity to cause change - Energy exists in various forms, some of which can perform work - Energy can be converted from one form to another (First Law of Thermodynamics) - Kinetic energy is energy associated with motion - Heat (thermal energy) is kinetic energy associated with random movement of atoms or molecules - Potential energy is energy that matter possesses because of its location or structure - Chemical energy is potential energy available for release in a chemical reaction The Laws of Energy Transformation An isolated system is unable to exchange energy or matter with its surroundings Example:liquid in a thermos In an open system, energy and matter can be transferred between the system and its surroundings Organisms are open systems The Second Law of Thermodynamics During every energy transformation, some energy is unusable, and often lost as heat Second law of thermodynamics Every energy transfer transformation increases entropy (disorder) of universe Figure 8.3b Entropy Biological Order and Disorder Cells create ordered structures from less ordered materials Requires the input of energy Order as a Characteristic of Life Evolution of more complex organisms does not violate the second law of thermodynamics Entropy (disorder) may decrease in an organism, but universe’s total entropy increases Figure 8.4 Free-Energy Change, DG Living system’s free energy is energy that can do work Enzymes facilitate metabolism Lower the energy requirements needed to start a chemical reaction Enzymes are specific for their substrates The specific shape of an enzyme permits this Complimentary fit with its substrate The fit isn’t initially perfect: the Induced-fit model How might you experimentally demonstrate that substrates alter the conformation of their enzymes? Genetic disorders and mutated enzyme genes Phenylketonuria (PKU) PKU Newborns with PKU have musty smelling urine PKU, untreated, can lead to severe mental deficits, seizures, etc Deficits in the enzyme phenylalanine hydroxylase Substrate is amino acid called phenylalanine, converting it into another amino acid (tyrosine) Testing for PKU is routinely done shortly after birth Treatment is dietary Ch.9 Cellular respiration Living cells require energy from outside sources Some animals obtain energy by eating plants, others eat organisms that eat plants The stages of cellular respiration include glycolysis, pyruvate oxidation, the citric acid or Krebs cycle, and oxidative phosphorylation. Krebs cycle produces the most ATP (adenosine triphosphate, an energy-carrying molecule found in the cells of all living things. ATP captures chemical energy obtained from the breakdown of food molecules and releases it to fuel other cellular processes.) Life Is Work Energy flows into an ecosystem in the form of sunlight and ultimately leaves as heat Photosynthesis generates organic molecules and O2, which are used in cellular respiration Cells use chemical energy stored in organic molecules to generate ATP, which powers cellular work Energy Flow and Chemical Recycling in Ecosystems Figure 9.2 Cellular respiration overview Key points Complex organic molecules contain potential energy in covalent bonds between their atoms  Catabolic pathways of Cellular Respiration release stored energy by breaking them down to simpler products Rearranging chemical bonds to release energy involves electron transfer Catabolic Pathways and Production of ATP cellular respiration is usually associated with the sugar glucose: C6H12O6 + 6 O2 ® 6 CO2 + 6 H2O + Energy (ATP + heat) Redox Reactions: Oxidation and Reduction Transfer of electrons during chemical reactions releases energy stored in organic molecules The energy of these electrons are ultimately used to synthesize ATP The Principle of Redox Chemical reactions that transfer electrons between reactants are called oxidation-reduction reactions, or redox reactions In oxidation, a substance loses electrons, or is oxidized In reduction, a substance gains electrons, or is reduced (“reduced”, because the amount of positive charge is reduced by the addition of a negatively charged electron) “LEO GER” Non-biological example During cellular respiration, glucose is oxidized, and O2 is reduced The Stages of Cellular Respiration Harvesting of energy from glucose occurs in three stages: - Glycolysis (breaks down glucose into two molecules of pyruvate(a.k.a.,pyruvic acid)) - Pyruvate Oxidation And The Citric Acid Cycle (or Krebs cycle) (complete breakdown of glucose) - Oxidative Phosphorylation (accounts for 90% of ATP synthesis) For each molecule of glucose broken down to CO2 and water by respiration, the cell makes up to 32 ATP Glycolysis Harvests Chemical Energy by Oxidizing Glucose to Pyruvate - Glycolysis = “splitting of sugar” - Breaks down glucose into molecules of pyruvate 10-step pathway Occurs In Cytosol Spending money (ATP) to make money (ATP) during glycolysis Figure 9.8 A Closer Look at Glycolysis Figure 9.9 Citric Acid Cycle Completes Energy-Yielding Oxidation of Organic Molecules In presence of O2, pyruvate enters the mitochondrion (in eukaryotic cells) where oxidation continues - Pyruvate oxidation links glycolysis and the citric acid cycles and involves 3 reactions: - One carbon is released as CO2 - NAD+ is reduced to form NADH - Acetate is linked to coenzyme A to form Acetyl-CoA Oxidation of Pyruvate to Acetyl CoA, the Step Before the Citric Acid Cycle Figure 9.10 The Citric Acid Cycle The acetyl group from acetyl-CoA enters the citric acid cycle (also called Krebs cycle) to complete the breakdown of pyruvate to CO2 eight steps, each catalyzed by a specific enzyme NADH and FADH2 produced during the cycle carry high-energy electrons extracted from food to the electron transport chain During glycolysis, pyruvate oxidation and the citric acid cycle, most of the energy extracted from organic molecules is transferred to NADH and FADH2  Both donate electrons to the electron transport chain, which powers ATP synthesis via oxidative phosphorylation Electron Transport The electron transport chain is located in the inner mitochondrial membrane (cristae) Most of the chain’s components include proteins Electron carriers alternate between reduced and oxidized states as they accept and donate electrons Free-Energy Change During Electron Transport Electrons give up free energy as they move through the chain in a stepwise fashion, and are ultimately donated to O2, forming H2O Figure 9.13 The Pathway of Electron Transport Electrons from NADH and FADH2 are passed through a series of electron carriers, including cytochromes, ultimately to O2 The ETC does not generate ATP directly It breaks the large free-energy drop from NADH and FADH2 to O2 into smaller steps that release energy in manageable amounts Chemiosmosis: The Energy-Coupling Mechanism The energy that is released during electron transfer through the ETC is used to pump H+ (proton) from the mitochondrial matrix to the intermembrane space, generating a gradient H+ then flow down their concentration gradient back across the inner membrane, through ATP synthase ATP synthase uses the flow of H+ to drive phosphorylation (adding a phosphate group) of ADP to form ATP This process is called chemiosmosis, the use of energy in a H+ gradient to drive cellular work ATP Synthase, a Molecule Motor Chemiosmosis Couples the Electron Transport Chain to ATP Synthesis Figure 9.16 Chemiosmosis Couples the Electron Transport Chain to ATP Synthesis Energy stored in the H+ gradient across the inner mitochondrial membrane couples the redox reactions of the electron transport chain to ATP synthesis ATP Yield Per Molecule of Glucose at Each Stage of Cellular Respiration Figure 9.17 The Catabolism of Different Organic Molecules from Food Figure 9.20 Chapter 11: Cellular Communication External signals are converted to internal responses within the cell Overview: Cellular Messaging Cells communicate to each other via chemical signals interpret signals they receive vital and universal Cellular Messaging For example, the fight-or-flight response is triggered by a signalling molecule called epinephrine Figure 11.1 Communication in yeast yeast have two mating types, a and a Cells of different mating types locate each other via secreted factors specific to each type Figure 11.2 Evolution of Cell Signalling Pathway similarities suggest that they started with ancestral prokaryotes Local and Long-Distance Signalling Animal and plant cells have cell junctions that allow local signalling by directly passing signalling molecules between adjacent cells Figure 11.4a Local signalling may also be achieved in animal cells by direct contact, or cell-cell recognition Figure 11.4b Signalling Animal cells can communicate using local regulators (travel only short distances) - Examples:Paracrine Signalling(e.g.growth hormones,and Synaptic signalling (e.g. neurotransmitters) Figure 11.5a,b In long-distance signalling, plants and animals use chemicals called hormones - Called Endocrine signalling in animals; uses circulatory system Figure 11.5c The Three Stages of Cell Signalling Earl Sutherland discovered how epinephrine acts on cells He suggested cells receiving signals went through three processes 1. Reception 2. Transduction 3. Response Overview of Cell Signaling 1. Reception:the target cell detect signalling molecule that binds to a receptor at the cell surface 2. Transduction:reception signal causes receptor to initiate a signal transduction pathway (usually a series of steps) 3. Response:the transduced signal triggers specific response in the target cell Figure 11.6 Reception Binding between signal molecule (ligand) and receptor (typically transmembrane proteins) is highly specific A conformational change in a receptor is often the initial transduction of signal How could you detect this experimentally? Cell-Surface Transmembrane Receptors Hydrophilic signal molecules bind cell- surface receptor proteins that span the plasma membrane There are three main types of membrane receptors - G Protein-coupled receptors(GPCRs) - Receptor Tyrosine Kinases(RTKs) - on Channel Receptors Receptors in the Plasma Membrane G protein-coupled receptors (GPCRs) are the largest family of cell-surface receptors (a.k.a., 7TM or “serpentine” receptors) - Abnormal Receptors Are Often Associated With Diseases Determiningtheirstructuremayleadtobetterdrugs Cell-Surface Transmembrane Receptors A GPCR is a plasma membrane receptor that works with a G protein  G protein acts as an on/off switch: If GDP is bound to protein, it is inactive G Protein Is Active When bound to GTP Figure 11.8 G proteins alpha, beta, gamma subunits comprise a G protein How epinephrine works Epinephrine is in a class of medications called alpha- and beta-adrenergic agonists (sympathomimetic agents). It works by relaxing the muscles in the airways and tightening the blood vessels. (Aka, adenylyl cyclase) (cAMP) (Kinases phosphorylate substrates) Activates Phosphorylase kinase Activates Glycogen phosphorylase Glycogen breakdown to glucose 213 Cell-Surface Transmembrane Receptors Receptor tyrosine kinases (RTKs) are membrane receptors that attach phosphates to tyrosines can trigger multiple signal transduction pathways Abnormal function associated with many cancers RTKs Figure 11.8 Ligand will cause RTKs to “dimerize” Trans Autophosphorylation – RTKs phosphorylating themselves! RTK mutations and cancer E.g., HER2 receptor Overly active in some breast cancers Mutations most often in kinase domain Ion channels Ligand-gated ion channel receptor acts as gate when it changes shape allows specific ions, such as Na+ or Ca2+, through a channel Figure 11.8 Intracellular Receptors Intracellular receptor proteins are found in the cytosol or nucleus Small or hydrophobic chemical messengers readily cross the membrane and activate these receptors Intracellular Receptors E.g., steroid and thyroid hormones in animals An activated hormone-receptor complex can act as transcription factor, turning on specific genes Small Molecules and Ions as Second Messengers Ligands are “first messengers” Second messengers are small, nonprotein molecules or ions, that freely diffuse inside the cell  initiated by GPCRs and RTKs Cyclic AMP (cAMP) and calcium (Ca2+) ions are common second messengers Cyclic AMP The bacterium that causes cholera, Vibrio cholerae, produces a toxin that modifies a G protein so that it is stuck in its active form causes intestinal cells to secrete large amounts of salt What would the water inside these cells do in this situation? Calcium Ions Ca2+ is an important second messenger because cells can regulate its concentration Figure 11.13 Calcium Ions Signal relayed by a signal transduction pathway may trigger an increase in calcium in cytosol Many enzymes are calcium-dependent DAG and IP3 Pathways leading to release of Ca2+ involve IP3 and DAG as additional second messengers Figure 11.14 Nuclear and Cytoplasmic Responses Many signalling pathways regulate protein synthesis by turning genes on or off Final activated molecule in signalling pathway may be a transcription factor Figure 11.15 Regulation of the Response A response to a signal might not necessarily be simply “on” or “off” There are four aspects of regulating, or fine-tuning, of a response to consider  1. Amplification of the signal (and thus the response) 2. Specificity of the response 3. Overall efficiency of response, enhanced by scaffolding proteins (linked to the cytoskeleton) 4. Termination of the signal Signal Amplification Enzyme cascades amplify the cell’s response At each step, the number of activated products is much greater than in the preceding step The Specificity of Cell Signalling and Coordination of the Response Different cells produce different collections of proteins These different proteins allow cells to detect and respond to different signals Also means that the same signal can lead to different responses in different cell types Pathway branching and “cross-talk” further help the cell coordinate incoming signals Figure 11.17 Termination of the Signal Inactivation mechanisms are an essential aspect of cell signalling If ligand concentration falls, fewer receptors will be bound Unbound receptors revert to an inactive state