HHP3550 Human Physiology Chapter 1: PDF Textbook

HHP:3550 Human Physiology CHAPTER 1 STRUCTURAL ORGANIZATION OF THE HUMAN BODY Cells, Tissues, Organs, & Organ Systems  LECTURE OUTLINE HHP:3550 I....

HHP:3550 Human Physiology CHAPTER 1 STRUCTURAL ORGANIZATION OF THE HUMAN BODY Cells, Tissues, Organs, & Organ Systems  LECTURE OUTLINE HHP:3550 I. Overview of Course Organization II. Introduction to Human Physiology III. Review of Structural Characteristics & Body Organization Important for Human Physiology I. Structure/Function Principles II. Tissue Types III. Organs IV. Organ Systems IV. Summary Chapter 1 - Introduction to the Human Body 2  I. OVERVIEW OF COURSE HHP:3550 ORGANIZATION ❑ UNIT 1: Foundational Concepts – Principles of Homeostasis (Ch. 1) – Chemical Composition of the Body: What Are We Made Of? (Ch. 2) – Overview of Eukaryotic Cells: Cell Membrane, Organelles (Ch. 3) – Proteins & The Human Body (Ch. 3) – Energy to Power Biological Activities (Ch. 3) – The Cell Membrane: Regulator of Transcellular Transport & Communication (Ch. 4- 5) Chapter 1 - Introduction to the Human Body 3  I. OVERVIEW OF COURSE HHP:3550 ORGANIZATION ❑ UNIT 2 – Nervous System (Ch. 6) ▪ Autonomic NS ▪ Somatic NS ▪ Sensory Systems (Ch. 7) – Muscular System (Ch. 9) ▪ Nervous System Control of Movement (Ch. 10) – Endocrine System (Ch. 11) Chapter 1 - Introduction to the Human Body 4  I. OVERVIEW OF COURSE HHP:3550 ORGANIZATION ❑ UNIT 3 – Cardiovascular (Ch. 12) – Immune System (Ch. 18) – Respiratory System (Ch. 13) Chapter 1 - Introduction to the Human Body 5  I. OVERVIEW OF COURSE HHP:3550 ORGANIZATION ❑ UNIT 4 – Renal System (Ch. 15) – Digestive System (Ch. 16) – Whole-Body Metabolism (also Ch. 16) – Reproductive Systems (Ch. 17) Chapter 1 - Introduction to the Human Body 6  II. INTRODUCTION TO HHP:3550 HUMAN PHYSIOLOGY ❑ Physiology is the study of how living organisms function ❑ Concept #1: Hierarchy of Structural Organization (Levels of Structural Organization) Molecules → cells → tissues →organs (functional units) → organ systems → organism ❑ Concept #2: Integrated Physiological Function: to understand physiology, we must understand how changes in function at each level lead to whole- body responses Chapter 1 - Introduction to the Human Body 7  II. INTRODUCTION TO HHP:3550 HUMAN PHYSIOLOGY ❑ Concept #3: Interrelationships between structure (anatomy) and function (physiology) – Review cell division and cell differentiation – Identify the four cell/tissue types: 1. Muscle cells 2. Neurons: cells of the Nervous System 3. Epithelial cells 4. Connective-tissue cells Chapter 1 - Introduction to the Human Body 8  III. REVIEW OF STRUCTURAL CHARACTERISTICS HHP:3550 TISSUES: MUSCLE TISSUE 1. Muscle Tissue Function: Mechanical force generation Chapter 1 - Introduction to the Human Body 9  III. REVIEW OF STRUCTURAL CHARACTERISTICS HHP:3550 TISSUES: NERVOUS TISSUE 2. Neuron Function: Communication via generation of electrical signals Chapter 1 - Introduction to the Human Body 10  III. REVIEW OF STRUCTURAL CHARACTERISTICS HHP:3550 TISSUES: EPITHELIAL TISSUE 3. Epithelial Tissue Functions: A. Barrier: covers internal, external surfaces ▪ Compartmentalization ▪ Structures – Basement membrane – Basolateral side – Apical (luminal) side – Tight junctions B. Selective secretion and absorption of ions, organic molecules C. Protection Chapter 1 - Introduction to the Human Body 11  III. REVIEW OF STRUCTURAL CHARACTERISTICS HHP:3550 TISSUES: EPITHELIAL TISSUE 3. Epithelial Tissue Functions: Note Structure: Function relationships Chapter 1 - Introduction to the Human Body 12  III. REVIEW OF STRUCTURAL CHARACTERISTICS HHP:3550 TISSUES: CONNECTIVE TISSUE 4. Connective Tissue Functions: A. To “connect”, anchor, support different parts of the body Chapter 1 - Introduction to the Human Body 13  III. REVIEW OF STRUCTURAL CHARACTERISTICS HHP:3550 TISSUES: CONNECTIVE TISSUE 4. Connective Tissue Functions: B. Formation of the extracellular matrix: collagen and elastin (protein) fibers, polysaccharides Scaffolding Cell signaling Chapter 1 - Introduction to the Human Body 14  III. STRUCTURAL CHARACTERISTICS ORGANS HHP:3550 ❑ Organ: discrete structure that performs a specific function – Organs often comprised of all 4 cell/tissue types – Example: Heart Chapter 1 - Introduction to the Human Body 15  III. STRUCTURAL CHARACTERISTICS ORGANS HHP:3550 ❑ Organ: discrete structure that performs a specific function – Functional Unit: “working unit” of an organ – Example: Nephrons in kidneys Chapter 1 - Introduction to the Human Body 16  III. STRUCTURAL CHARACTERISTICS ORGANS HHP:3550 ❑ Organ System: several organs working together to perform an overall function in an organism ❑ Multiple organ systems will work cooperatively to maintain overall organismal function ❑ For us, the ‘organism’ is the human body Chapter 1 - Introduction to the Human Body 17  SUMMARY – TERMS & CONCEPTS HHP:3550 Physiology Organ system Organ Integrated physiological function Functional unit of an organ Structural Organization/Hierarchy (concept): cells → tissues → functional units within organs → organ systems → organism (human body) 4 Tissue Types: muscle, neural, epithelium, and connective tissues Epithelial Cell Structures: basement membrane, basolateral side, apical (luminal) side, tight junctions Chapter 1 - Introduction to the Human Body 18  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to … 1. Define physiology, and describe the levels at which it can be studied 2. Explain the concept of integrated physiological function and how the function of the whole body can be attributed to numerous internal processes 3. Describe the organizational (structural) hierarchy of humans: cells → tissues → organs → organ systems → organism/whole-body 4. Identify the four cell/tissue types and the primary functions of each, with specific attention given to epithelial cell characteristics Chapter 1 - Introduction to the Human Body 19  HHP:3550 Human Physiology CHAPTER 1 STRUCTURAL ORGANIZATION OF THE HUMAN BODY FLUID COMPARTMENTS  LECTURE OUTLINE HHP:3550 I. Body Fluid Compartments A. Typical Values B. Electrolyte Composition C. Ion/Water Movement II. Summary Chapter 1 - Introduction to the Human Body 21  I. BODY FLUID COMPARTMENTS HHP:3550 ❑ Concept: Body fluids (water plus the substances dissolved in it) are localized into 2 (3) compartments: 1. Intracellular fluid compartment (ICF): ~2/3 body water 2. Extracellular fluid compartment (ECF): ~1/3 body water A. Plasma B. Interstitial fluid (and interstitium) 60-40-20 rule Chapter 1 - Introduction to the Human Body 22  I. BODY FLUID COMPARTMENTS HHP:3550 TYPICAL VALUES How much is this for the “average person”? USA F ~170lbs → 93.5bs fluid → 63lbs ICF → 32lbs ECF M ~200lbs → 120bs fluid → 80lbs ICF → 40lbs ECF Dependent on body composition Chapter 1 - Introduction to the Human Body 23  I. BODY FLUID COMPARTMENTS HHP:3550 ELECTROLYTE COMPOSITION ❑ Electrolyte Composition – What are the major ions of the ECF? – Major ions of the ICF? – Note distribution of positive, negative ions Chapter 1 - Introduction to the Human Body 24  I. BODY FLUID COMPARTMENTS HHP:3550 ION/WATER MOVEMENT Concept: Flux Across Fluid Compartments Chapter 1 - Introduction to the Human Body 25  I. BODY FLUID COMPARTMENTS HHP:3550 ION/WATER MOVEMENT ❑ Concept: Steady state vs. Equilibrium Barriers for compartmentalization Chapter 1 - Introduction to the Human Body 26  SUMMARY - TERMINOLOGY HHP:3550 Fluid Compartments: intracellular, ICF extracellular, ECF: plasma, interstitium Concept of steady state values for physiological function, versus being in equilibrium Chapter 1 - Introduction to the Human Body 27  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Identify the two main fluid compartments; next, describe the location of the plasma and interstitial volumes 2. Provide reasonable numbers for the proportion of body water within the intracellular fluid compartment and the extracellular fluid compartment, including the plasma volume 3. Identify the major ions located within the extracellular fluid compartment and compare to the ions composition of the intracellular fluid compartment 4. Explain the concept of compartmentalization and recognize the importance of barriers between compartments that maintain the differences in composition of the various body fluids 5. Explain why “steady state” is not synonymous with “equilibrium” Chapter 1 - Introduction to the Human Body 28  HHP:3550 Human Physiology CHAPTER 1 HOMEOSTASIS & HOMEOSTATIC CONTROL SYSTEMS CHARACTERISTICS OF HOMEOSTASIS  LECTURE OUTLINE HHP:3550 I. Characteristics of Homeostasis A. Definition B. Example C. Integrated Function II. Feedback and Feedforward Control A. Negative Feedback B. Positive Feedback C. Feedforward Regulation III. Summary Chapter 1 - Introduction to the Human Body 30  I. CHARACTERISTICS OF HOMEOSTASIS HHP:3550 DEFINITION ❑ Homeostasis – The process by which physiological variables are kept relatively “stable” despite imposed challenges ▪ Examples of variables that are regulated, and specific challenges to maintaining stability for each variable? Chapter 1 - Introduction to the Human Body 31  I. CHARACTERISTICS OF HOMEOSTASIS HHP:3550 DEFINITION ❑ Homeostasis – The process by which physiological variables are kept relatively “stable” despite imposed challenges ▪ What does “stable” mean? Chapter 1 - Introduction to the Human Body 32  I. CHARACTERISTICS OF HOMEOSTASIS HHP:3550 EXAMPLE ❑ Homeostasis – Example: blood glucose regulation ▪ If glucose not regulated, what are the consequences? ▪ Challenges to regulation? ▪ What are the components of the system that keeps blood glucose in homeostasis (Sect 1.5 & 1.6)? Chapter 1 - Introduction to the Human Body 33  I. CHARACTERISTICS OF HOMEOSTASIS HHP:3550 EXAMPLE (CONT.) ❑ Homeostasis – Example: blood glucose regulation (cont.) ▪ Set point: regulated physiological range ▪ Steady state vs. equilibrium ▪ Steady state achieved by balancing inputs and outputs ▪ In this case, what is input? Output? Chapter 1 - Introduction to the Human Body 34  I. CHARACTERISTICS OF HOMEOSTASIS HHP:3550 INTEGRATED FUNCTION ❑ Each variable can be regulated independently, but regulation of one may influence regulation of another ▪ Integrated physiological function! Regulating body temp… …affects fluid balance Chapter 1 - Introduction to the Human Body 35  II. FEEDBACK AND FEEDFORWARD CONTROL HHP:3550 NEGATIVE FEEDBACK ❑ Homeostatic control systems utilize feedback or feed-forward control to regulate physiological variables around set point 1. Negative Feedback System: a change in a variable away from its set point initiates a response bringing it back towards its set point ▪ Organism-level example: body temperature regulation Chapter 1 - Introduction to the Human Body 36  II. FEEDBACK AND FEEDFORWARD CONTROL HHP:3550 POSITIVE FEEDBACK ❑ Homeostatic Control Systems 2. Positive Feedback System: a change in a variable away from set point causes a chain of events that further increase the change ▪ Example: childbirth ▪ Variables that are very low-level under “normal” conditions ▪ Serves homeostasis in a global sense How? Chapter 1 - Introduction to the Human Body 37  II. FEEDBACK AND FEEDFORWARD CONTROL HHP:3550 FEEDFORWARD REGULATION ❑ Homeostatic Control Systems 3. Feedforward Regulation: the body adjusts a variable prior to any actual change, in anticipation of future needs ▪ Examples? – Ventilation at the onset of exercise – Salivation prior to a meal ▪ Pros and Cons? Chapter 1 - Introduction to the Human Body 38  SUMMARY - TERMINOLOGY HHP:3550 Homeostasis dynamic constancy set point steady state (vs. equilibrium) negative feedback positive feedback feedforward regulation Chapter 1 - Introduction to the Human Body 39  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Define homeostasis, dynamic constancy of physiological variables, set point, steady state, and equilibrium 2. Explain the integrated nature of homeostatic control systems; i.e., how can regulation of one variable affect regulation of another? 3. Explain how negative feedback, positive feedback, and feedforward systems are similar and how they are different Chapter 1 - Introduction to the Human Body 40  HHP:3550 Human Physiology CHAPTER 1 HOMEOSTASIS & HOMEOSTATIC CONTROL SYSTEMS What Does a Homeostatic Control System Look Like?  LECTURE OUTLINE HHP:3550 I. Components of Homeostatic Control Systems A. Overview B. Homeostatic Reflexes C. Local Homeostatic Responses II. Intercellular Chemical Messengers A. Hormones B. Neurotransmitters C. Paracrine, Autocrine Agents III. Summary Chapter 1 - Introduction to the Human Body 42  I. COMPONENTS OF CONTROL SYSTEMS HHP:3550 OVERVIEW Homeostatic control systems regulate variables via reflexes and/or local responses; in both cases, cells must communicate with one another Chapter 1 - Introduction to the Human Body 43  I. COMPONENTS OF CONTROL SYSTEMS HHP:3550 HOMEOSTATIC REFLEXES 1. Homeostatic Reflexes: unlearned control systems linking stimuli with one (or more) responses, mediated by a reflex arc – *Components of Reflex Arc 1. Stimulus 2. Receptor 3. Afferent Pathway 4. Integrating Center 5. Efferent Pathway 6. Effector(s) 7. Response(s) Chapter 1 - Introduction to the Human Body 44  I. COMPONENTS OF CONTROL SYSTEMS HHP:3550 HOMEOSTATIC REFLEXES (EXAMPLE) ❑ Remember: – Homeostasis is integration ▪ Multiple stimuli, multiple effectors Chapter 1 - Introduction to the Human Body 45  I. COMPONENTS OF CONTROL SYSTEMS HHP:3550 LOCAL HOMEOSTATIC RESPONSES 2. Local Homeostatic Responses – Like a reflex, links a stimulus to a response – Unlike a reflex, occurs entirely within a local area ▪ No afferent pathway, no integrating center, no efferent pathway ▪ Example: Hyperemia Chapter 1 - Introduction to the Human Body 46  II. INTERCELLULAR CHEMICAL MESSENGERS HHP:3550 OVERVIEW ❑ Both reflexes and local responses require cellular communication, accomplished via intercellular chemical messengers – General process by which cells “talk” to one another? ❑ Important things to keep in mind regarding intercellular chemical messengers… – Categorized by which cells release them and where they are released (see coming slides) – Same messenger can play multiple roles Chapter 1 - Introduction to the Human Body 47  II. INTERCELLULAR CHEMICAL MESSENGERS HHP:3550 CLASSES OF MESSENGERS (HORMONES) ❑ Classes of Intercellular Chemical Messengers 1. Hormones Chapter 1 - Introduction to the Human Body 48  II. INTERCELLULAR CHEMICAL MESSENGERS HHP:3550 CLASSES OF MESSENGERS (HORMONES) ❑ Classes of Intercellular Chemical Messengers 1. Hormones 2. Neurotransmitters Chapter 1 - Introduction to the Human Body 49  II. INTERCELLULAR CHEMICAL MESSENGERS HHP:3550 CLASSES OF MESSENGERS (HORMONES) ❑ Classes of Intercellular Chemical Messengers 1. Hormones 2. Neurotransmitters 3. Paracrine agents 4. Autocrine agents Chapter 1 - Introduction to the Human Body 50  SUMMARY - TERMINOLOGY HHP:3550 homeostatic reflex local homeostatic response hormone Neurotransmitter paracrine/autocrine agents Chapter 1 - Introduction to the Human Body 51  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Define a homeostatic reflex, identify the components of a reflex arc, and explain how reflex arcs contribute to homeostasis 2. Compare and contrast reflexes and local homeostatic responses; describe the role that each plays in homeostasis of the organism 3. Explain how intercellular chemical messengers can contribute to homeostasis; identify and define the four different types Chapter 1 - Introduction to the Human Body 52  HHP:3550 Human Physiology CHAPTER 1 HOMEOSTASIS & HOMEOSTATIC CONTROL SYSTEMS Organism-Level Processes Related to Homeostasis  I. ORGANISM-LEVEL HOMEOSTATIC PROCESSES HHP:3550 OVERVIEW Homeostatic processes function at all physiological levels, but understanding how these processes are integrated at the organismal-level is ultimately the key to understanding human physiology. Chapter 1 - Introduction to the Human Body 54  LECTURE OUTLINE HHP:3550 I. Organism-Level Homeostatic Processes A. Evolution of Homeostatic Control Systems B. Biological Rhythms C. Balance of Substances in the Body II. Summary Chapter 1 - Introduction to the Human Body 55  I. ORGANISM-LEVEL HOMEOSTATIC PROCESSES EVOLUTION OF HOMEOSTATIC CONTROL SYSTEMS HHP:3550 ❑ Different homeostatic control systems have been acquired through evolution Different species have evolved different systems to deal with similar challenges/environments Chapter 1 - Introduction to the Human Body 56  I. ORGANISM-LEVEL HOMEOSTATIC PROCESSES EVOLUTION OF HOMEOSTATIC CONTROL SYSTEMS HHP:3550 ❑ These evolved systems possess the ability to change in response to chronic conditions – Examples? – Characteristics of these changes? ❑ We will not get bogged down in the specific terminology (i.e. adaptation/acclimatization) that the textbook uses to describe this acquisition and change Chapter 1 - Introduction to the Human Body 57  I. ORGANISM-LEVEL HOMEOSTATIC PROCESSES HHP:3550 BIOLOGICAL RHYTHMS Chapter 1 - Introduction to the Human Body 58  I. ORGANISM-LEVEL HOMEOSTATIC PROCESSES HHP:3550 BIOLOGICAL RHYTHMS ❑ Type of feedforward regulation ❑ Circadian rhythms cycle once every 24 hours Examples: Wakefulness, body temperature, various hormones 24-Hour Time Period ❑ Hypothalamus is the location of the primary pacemaker for these rhythms Chapter 1 - Introduction to the Human Body 59  I. ORGANISM-LEVEL HOMEOSTATIC PROCESSES HHP:3550 BALANCING SUBSTANCES IN THE BODY Chapter 1 - Introduction to the Human Body 60  I. ORGANISM-LEVEL HOMEOSTATIC PROCESSES HHP:3550 BALANCING SUBSTANCES IN THE BODY ❑ Many systems balance addition and removal of a given substance from a pool within the body – Note mechanisms for net gain and net loss – Examples of substances that are regulated? Chapter 1 - Introduction to the Human Body 61  I. ORGANISM-LEVEL HOMEOSTATIC PROCESSES BALANCING SUBSTANCES IN THE BODY (EXAMPLE) HHP:3550 Example: Sodium Chapter 1 - Introduction to the Human Body 62  I. ORGANISM-LEVEL HOMEOSTATIC PROCESSES BALANCING SUBSTANCES IN THE BODY (CHANGES) HHP:3550 ❑ Loss > gain = negative balance ❑ Gain > loss = positive balance ❑ Loss = gain = stable balance Chapter 1 - Introduction to the Human Body 63  SUMMARY - TERMINOLOGY HHP:3550 biological rhythm (& circadian rhythms) hypothalamus (a body structure) substance pool negative/positive/stable net balance Chapter 1 - Introduction to the Human Body 64  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Understand that homeostatic control systems are acquired through evolution, and these systems can be modified due to chronic changes in stimuli/environment 2. Explain the concept of biological rhythms and provide examples; identify the structure that typically coordinates biological rhythms 3. Define the “pool “ of a substance as the amount available for use and recognize that the substance can be added to or removed from the pool Chapter 1 - Introduction to the Human Body 65  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 4. Understand that the balance of substances in the body depends upon the relative rates of net gain and net loss 5. Identify mechanisms for net gain of a substance (i.e., how the amount of a substance found in the body can increase); next, identify mechanisms for net loss of a substance (i.e., how the amount of a substance can be reduced) 6. Describe how changing inputs and outputs of the substances can induce negative, positive, or stable balance Chapter 1 - Introduction to the Human Body 66  HHP:3550 Human Physiology CHAPTER 2 A Physiologist’s View of Chemistry Principles  GENERAL PRINCIPLES OF PHYSIOLOGY HHP:3550 Physiological processes are dictated by the laws of chemistry and physics Vitamin C (Ascorbic Acid) Chemical Structure Chapter 2 - Chemicals of Life 68  LECTURE OUTLINE HHP:3550 I. Atoms and Elements II. Molecules III. Solutions IV. Classes of Organic Molecules - Introduction V. Summary Chapter 2 - Chemicals of Life 69  I. ATOMS AND ELEMENTS HHP:3550 Atom: the smallest freely existing unit of matter Chemistry Physiology Atomic Human body is Structure: composed of Nucleus: protons (+), elements neutrons Atomic variants can be Orbitals (shells): measured and used electrons (-) clinically Atomic number Electrons in orbitals are important in forming Atomic mass molecular bonds Chapter 2 - Chemicals of Life 70  I. ATOMS AND ELEMENTS HHP:3550 COMPOSITION OF THE HUMAN BODY ❑ The human body is composed of 24 essential elements – Major elements* – Mineral elements ▪ Calcium, potassium, sodium ▪ Trace (mineral) elements Chapter 2 - Chemicals of Life 71  I. ATOMS AND ELEMENTS: ATOMIC VARIANTS HHP:3550 ISOTOPES AND RADIOISOTOPES ❑ Variants of many elements exist based upon PET scan using neutron # Fluoro-deoxyglucose – Isotopes – Examples: 1H, 2H, 3H 12C, 13C, 14C – Radioisotopes tend to be unstable ▪ Cancer treatments ▪ Diagnostic medicine ▪ Examples: doubly-labeled water (2H218O), 18F- FDG Chapter 2 - Chemicals of Life 72  I. ATOMS AND ELEMENTS: ATOMIC VARIANTS HHP:3550 IONS ❑ If an atom gains or loses an electron, it becomes an ION Ion: atom that gains or loses one or more electrons in order to achieve a full outer shell, resulting in a net charge Cations, anions Electrolyte: ion in solution Chapter 2 - Chemicals of Life 73  I. ATOMS AND ELEMENTS: ATOMIC VARIANTS HHP:3550 IONS: PRACTICAL CONNECTION ❑ We Exercise = We Sweat Sweat causes water, electrolyte losses from the body Disrupts homeostasis Chapter 2 - Chemicals of Life 74  II. MOLECULES & MOLECULAR BONDS HHP:3550 OVERVIEW Molecule: two or more atoms bonded together Chapter 2 - Chemicals of Life 75  II. MOLECULES HHP:3550 TYPES OF MOLECULAR BONDS ❑ Atoms within a molecule can be held together by covalent bonds (non-polar or polar) or ionic bonds Polar vs. non-polar covalent bonds Chapter 2 - Chemicals of Life 76  II. MOLECULES & MOLECULAR BONDS HHP:3550 COVALENT BONDS ❑ Molecules containing many polar bonds behave differently from molecules containing many non- polar bonds Examples of polar molecules? Examples of nonpolar molecules? Chapter 2 - Chemicals of Life 77  II. MOLECULES & MOLECULAR BONDS HHP:3550 HYDROGEN BONDS Hydrogen bonds – attraction between a partially positive H in one molecule with a partially negative atom in another molecule – Strength? – Significance? Chapter 2 - Chemicals of Life 78  II. MOLECULES & MOLECULAR BONDS HHP:3550 MOLECULES AS IONS ❑ Molecules, just like atoms, can gain or lose electrons to become ions – Electron from a H can be captured, releasing a H+ and forming an anion – Alternately, a molecule can bind a H+, becoming a cation Chapter 2 - Chemicals of Life 79  II. MOLECULES & MOLECULAR BONDS HHP:3550 FREE RADICALS ❑ Free radicals: molecules with an unpaired electron in outermost orbital – Formed naturally within body – Can be formed due to exposure to radiation or toxins – Reactive oxygen species (ROS) – Oxidative stress leads to damage of macromolecules Chapter 2 - Chemicals of Life 80  II. MOLECULES & MOLECULAR BONDS HHP:3550 FREE RADICALS ROS can lead to oxidative stress and damage to macromolecules, but they are also important signaling molecules ROS trigger pathways leading to many positive adaptations within the body Cell Signal. 2012 May; 24(5): 981–990. Chapter 2 - Chemicals of Life 81  III. SOLUTIONS & PH HHP:3550 OVERVIEW ❑ The majority of your body is made up of water, and “physiology” occurs within an aqueous environment – Solvent: liquid component of a mixture – Solute: substance dissolved in liquid – Solution: solvent + solutes – Example: blood glucose concentration Chapter 2 - Chemicals of Life 82  III. SOLUTIONS & PH HHP:3550 SOLUBILITY IN WATER ❑ Molecular solubility: how well a solute will dissolve in a solvent – Polar, ionic molecules dissolve in water: hydrophilic, lipophobic – Non-polar compounds are generally insoluble in water: hydrophobic, lipophilic – Compounds with a polar region and a non-polar region are amphipathic Chapter 2 - Chemicals of Life 83  III. SOLUTIONS & PH HHP:3550 SOLUBILITY IN WATER ❑ Physiological implications … – Transport in blood – Movement of molecules across cell membranes Chapter 2 - Chemicals of Life 84  III. SOLUTIONS & PH HHP:3550 WATER AS A REAGENT In addition to being the solvent of the body, water (H20) is also reagent involved in making and breaking covalent bonds Molecules Monomers (Polymers) Chapter 2 - Chemicals of Life 85  III. SOLUTIONS & PH HHP:3550 ACIDITY & ALKALINITY ❑ When a H atom loses an electron, it becomes a single, free proton (H+) [H+] relates to acidity, measured by pH pH = -log [H+] ❑ Other “Fun Facts”: – Intracellular Fluid pH ≈ 7.2 – Extracellular Fluid pH ≈ 7.4 Chapter 2 - Chemicals of Life 86  III. SOLUTIONS & PH HHP:3550 ACIDITY & ALKALINITY ❑ Physiological Significance of pH – Signaling mechanism – Impacts proteins (including enzymes) – Example: acidosis during exercise alters enzyme activity of metabolic pathways to increase ATP production – Disruption of acid-base balance challenges homeostasis: buffering systems Chapter 2 - Chemicals of Life 87  IV. CLASSES OF ORGANIC MOLECULES HHP:3550 OVERVIEW What are we made of? Body composition classification schemes Chapter 2 - Chemicals of Life 88  IV. CLASSES OF ORGANIC MOLECULES HHP:3550 OVERVIEW ❑ Living organisms are comprised of carbon- containing molecules ❑ 4 categories of macromolecules in the human body 1. Carbohydrates 2. Lipids 3. Proteins 4. Nucleic acids Chapter 2 - Chemicals of Life 89  SUMMARY - TERMINOLOGY HHP:3550 Atomic Terminology: atom, element, isotope, ion (cation, anion), electrolyte, Molecular Terminology: molecule, covalent bond, ionic bond, polarity, nonpolar bond, polar bond, hydrogen bond, free radical (ROS), oxidative stress Solution Terminology: solute, solvent, solution, solubility, concentration, hydrophobic (lipophilic), hydrophilic (lipophobic), amphipathic, pH Chapter 2 - Chemicals of Life 90  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Describe the three subatomic particles that constitute the atom, their atomic locations, and how each one contributes to atom function 2. Explain the relationship between the number of electrons within the outermost orbital and atomic stability 3. Describe what isotopes are and how they can be used in medicine 4. List the four major elements that comprise human body; identify the major cations and anions that are found in the human body 5. Identify the two types of chemical bonds that can form molecules Chapter 2 - Chemicals of Life 91  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 6. Describe the differences between polar and non-polar covalent bonds, and provide common examples of each 7. Provide examples of polar molecules, nonpolar molecules, and ionic molecules; describe how a molecule’s polarity affects its interaction with other molecules 8. Explain how a hydrogen bond differs from true chemical bonds (e.g. covalent and ionic), and explain why hydrogen bonds are important in biochemistry 9. Explain how the terms solute, solvent, solution, solubility, and concentration are related to one another Chapter 2 - Chemicals of Life 92  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 10. Understand that water is the solvent of the body and is polar; understand how polar, non-polar, and amphipathic substances will react when mixed with water 11. Understand how pH relates to H+ concentration in solution and what it means to be acidic or basic 12. List the four classes of organic macromolecules found in the human body Chapter 2 - Chemicals of Life 93  HHP:3550 Human Physiology CHAPTER 2 Carbohydrates  LECTURE OUTLINE HHP:3550 I. Carbohydrates A. Function B. Structure C. Practical Example II. Summary Chapter 2 - Chemicals of Life 95  I. CARBOHYDRATES HHP:3550 FUNCTION ❑ Carbohydrates make up only 1% of body weight ❑ Function: cellular energy production – Adenosine triphosphate, ATP – Especially important… ▪ During exercise ▪ As the primary energy substrate in certain tissues Examples: » Nervous system » Retina » Red blood cells Chapter 2 - Chemicals of Life 96  I. CARBOHYDRATES HHP:3550 FUNCTION ❑ To Review (and Preview): – Carbohydrates as part of the extracellular matrix (glycocalyx), aiding in cell recognition and cell signaling ▪ Note glycoprotein, glycolipid structures Chapter 2 - Chemicals of Life 97  I. CARBOHYDRATES HHP:3550 STRUCTURE ❑ Structure: Cn(H2O)n – Most CHO contain a hydroxyl – (OH) group ▪ Polar or non-polar? – Subunits = monosaccharides 1. Glucose (6 C) 2. Galactose (6 C) 3. Fructose (5 C) Chapter 2 - Chemicals of Life 98  I. CARBOHYDRATES HHP:3550 STRUCTURE ❑ Disaccharides – 2 monosaccharides linked via dehydration reactions – Hydrolysis reactions? ❑ Polysaccharides Chapter 2 - Chemicals of Life 99  II. CARBOHYDRATES HHP:3550 STRUCTURE ❑ Disaccharides ❑ Polysaccharides: – Linked monosaccharides – Function: CHO storage ▪ Starch: primary plant polysaccharide ▪ Glycogen: primary animal polysaccharide – Storage sites: liver, skeletal muscle – Note extensive branching – Benefit? Chapter 2 - Chemicals of Life 100  I. CARBOHYDRATES HHP:3550 PRACTICAL EXAMPLES How does the figure below relate to the topic of carbohydrates? Chapter 2 - Chemicals of Life 101  I. CARBOHYDRATES HHP:3550 SUMMARY ❑ Living organisms are comprised of carbon- containing molecules ❑ 4 categories of (organic) macromolecules in the human body 1. Carbohydrates 2. Lipids 3. Proteins 4. Nucleic acids Chapter 2 - Chemicals of Life 102  SUMMARY - TERMINOLOGY HHP:3550 macromolecule adenosine triphosphate, ATP extracellular matrix: glycocalyx monosaccharides: glucose, galactose, fructose disaccharides polysaccharide: glycogen Chapter 2 - Chemicals of Life 103  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. List the four classes of organic macromolecules found in the human body 2. Describe the structures and functions of carbohydrates 3. Understand that monosaccharides are the subunits of carbohydrates, and these can be combined to form disaccharides and polysaccharides 4. Identify glucose as an important monosaccharide and glycogen as an important polysaccharide in the human body Chapter 2 - Chemicals of Life 104  HHP:3550 Human Physiology CHAPTER 2 Lipids  LECTURE OUTLINE HHP:3550 I. Lipids A. Functions B. Structure C. Sub-Classes II. Summary Chapter 2 - Chemicals of Life 106  I. LIPIDS HHP:3550 STRUCTURE ❑ Structure: mostly C and H atoms linked by covalent bonds – Polar or non-polar? – Water solubility? Chapter 2 - Chemicals of Life 107  I. LIPIDS HHP:3550 SUB-CLASSES ❑ 4 Lipid Sub-Classes: 1. Fatty Acids (FA): long C chain with attached H, COOH at one end ▪ Saturated versus unsaturated fatty acids ▪ Functions: ATP synthesis, building blocks for other lipids Chapter 2 - Chemicals of Life 108  SO WHAT ARE… HHP:3550 …TRANS FATS? 1. Fatty Acids (FA): – Hydrogenation of fatty acids – creates atypical FA structure – Pros: food palatability, shelf life – Cons: alters blood cholesterol Chapter 2 - Chemicals of Life 109  I. LIPIDS HHP:3550 SUB-CLASSES ❑ 4 Lipid Sub-Classes: 2. Triglycerides: “fats”; primary storage form of lipids in the body (body fat) ▪ 3 FAs linked to glycerol (3-C sugar alcohol) ▪ FAs within a TG can be saturated or unsaturated Chapter 2 - Chemicals of Life 110  I. LIPIDS HHP:3550 SUB-CLASSES ❑ 4 Lipid Sub-Classes: 3. Phospholipids: glycerol + 2 FAs + 1 phosphate group + a nitrogen (N) -containing molecule ▪ How would we describe resulting polarity? ▪ Function: primary component of plasma membranes Chapter 2 - Chemicals of Life 111  I. LIPIDS HHP:3550 SUB-CLASSES ❑ 4 Lipid Sub-Classes: 4. Steroids ▪ Structure: 4 interconnected rings of C atoms, a few hydroxyls (OH) ▪ Derived from ▪ cholesterol ▪ Non-polar Solubility in body fluids? Chapter 2 - Chemicals of Life 112  I. LIPIDS HHP:3550 SUB-CLASSES ❑ 4 Lipid Sub-Classes: 4. Steroids ▪ Functions: – Important component of plasma membranes – Component of steroid hormones » Examples? Chapter 2 - Chemicals of Life 113  I. LIPIDS HHP:3550 SUMMARY ❑ Living organisms are comprised of carbon- containing molecules ❑ 4 categories of macromolecules in the human body 1. Carbohydrates 2. Lipids 3. Proteins 4. Nucleic acids Chapter 2 - Chemicals of Life 114  SUMMARY - TERMINOLOGY HHP:3550 fatty acid, FA unsaturated FA triglyceride, TG phospholipid cholesterol saturated FA trans fats glycerol steroid molecules Chapter 2 - Chemicals of Life 115  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Identify and describe the structures/functions for each of the four subclasses of lipids 2. Differentiate between saturated, unsaturated, and trans fatty acids 3. Comment upon the general polarity of lipids and solubility in body fluids Chapter 2 - Chemicals of Life 116  HHP:3550 Human Physiology CHAPTER 2 Proteins  LECTURE OUTLINE HHP:3550 I. Protein Overview A. Prevalence and Composition B. Function C. Amino Acids II. Protein Shape A. Importance B. Primary, Secondary, Tertiary, and Quaternary Structure C. Denaturation Summary Chapter 2 - Chemicals of Life 118  I. PROTEIN OVERVIEW HHP:3550 PREVALENCE AND COMPOSITION ❑ Proteins make up 17% of body weight and ~50% of the organic material in the body – Large macromolecules – Contain C, H, O, N, and possibly S Insulin (~6 kDa) Chapter 2 - Chemicals of Life 119  I. PROTEIN OVERVIEW HHP:3550 FUNCTIONS ❑ Proteins are critical to all physiological processes – Regulate gene expression (transcription factors, RNA polymerase, ribosomal proteins) – Mediate movement of solutes across plasma membranes (ion channels and transporter proteins) – Accelerate the rate of specific chemical reactions (enzymes) – Participate in cell signaling (hormones, neurotransmitters, autocrine/paracrine agents) – Support, connect, and strengthen cells, tissue, and organs (structural proteins) – Protect against pathogens (cytokines and antibodies) Chapter 2 - Chemicals of Life 120  I. PROTEIN OVERVIEW HHP:3550 AMINO ACIDS Proteins are composed of amino acid subunits, and all living organisms use the same 20 amino acids Chapter 2 - Chemicals of Life 121  I. PROTEIN OVERVIEW HHP:3550 AMINO ACIDS (STRUCTURE) ❑ Amino acids have the same general structure but differ in their side chains (i.e. R groups) ▪ Central Carbon connected to… ▪ H ▪ Carboxyl group ▪ Amino group ▪ Side chain (R) Chapter 2 - Chemicals of Life 122  I. PROTEIN OVERVIEW HHP:3550 AMINO ACIDS (PEPTIDE BONDS) ❑ Amino acids linked together by peptide bonds to form polypeptides ▪ < 50 AAs with biological function = peptide ▪ > 50 AAs with characteristic shape and function = protein Chapter 2 - Chemicals of Life 123  II. PROTEIN SHAPE HHP:3550 IMPORTANCE Protein shape (and its ability to change) is the basis of all physiological function Protein shape determined by different levels of structure (primary, secondary, tertiary, and quaternary) Chapter 2 - Chemicals of Life 124  II. PROTEIN SHAPE HHP:3550 PRIMARY STRUCTURE Primary structure: the # and types of amino acids and their specific order Chapter 2 - Chemicals of Life 125  II. PROTEIN SHAPE HHP:3550 SECONDARY STRUCTURE ❑ Secondary structure: local folding – α-helices, β pleated sheets, and random coiled regions – Hydrogen bonds between amino and carboxyl groups Chapter 2 - Chemicals of Life 126  II. PROTEIN SHAPE HHP:3550 TERTIARY STRUCTURE ❑ Tertiary structure: global, 3D folding – Due to interactions between side chains ▪ H bonds ▪ Ionic bonds ▪ Hydrophobic bonds ▪ Covalent (disulfide) bonds ▪ van der Waals forces Chapter 2 - Chemicals of Life 127  II. PROTEIN SHAPE HHP:3550 QUATERNARY STRUCTURE ❑ Quaternary structure: the combination of multiple polypeptides to make a single protein – Also due to interaction of side-chains – Results in Multimeric protein – Example: Hemoglobin Chapter 2 - Chemicals of Life 128  II. PROTEIN SHAPE HHP:3550 DENATURATION ❑ Denaturation: loss of 3D shape and therefore biological function What causes protein “unfolding”? Chapter 2 - Chemicals of Life 129  II. PROTEIN SHAPE HHP:3550 DENATURATION (PROTEIN CHAPERONES) ❑ Denaturation: loss of 3D shape and therefore biological function Can proteins ever be repaired? Chapter 2 - Chemicals of Life 130  I. PROTEINS HHP:3550 SUMMARY ❑ Living organisms are comprised of carbon- containing molecules ❑ 4 categories of macromolecules in the human body 1. Carbohydrates 2. Lipids 3. Proteins 4. Nucleic acids Chapter 2 - Chemicals of Life 131  SUMMARY - TERMINOLOGY HHP:3550 amino acid, side chain peptide bond, polypeptide, protein primary structure, secondary structure, tertiary structure, quaternary structure multimeric protein denaturation, protein chaperones, heat shock proteins Chapter 2 - Chemicals of Life 132  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Detail the general roles played by proteins within physiology 2. Describe the structural components of amino acids and how they bond together to form polypeptides 3. Explain how protein shape is determined by primary, secondary, tertiary, and quaternary structure; explain why protein shape is so important 4. Define denaturation and explain its consequences 5. Describe the role of protein chaperones in determining and preserving protein shape Chapter 2 - Chemicals of Life 133  HHP:3550 Human Physiology CHAPTER 2 Nucleic Acids  LECTURE OUTLINE HHP:3550 I. Nucleic Acids A. Overview B. 2 Classes C. Nucleotides II. Deoxyribonucleic Acid (DNA) III. Ribonucleic Acid (RNA) Chapter 2 - Chemicals of Life 135  I. NUCLEIC ACIDS HHP:3550 OVERVIEW ❑ Nucleic acids make up 2% of body weight and 8% of organic material in the human body ❑ Function: Responsible for storage and expression of genetic information What does this mean? Chapter 2 - Chemicals of Life 136  I. NUCLEIC ACIDS HHP:3550 TWO CLASSES ❑ There are two classes of nucleic acic ▪ Deoxyribonucleic Acid (DNA): ▪ Stores genetic information ▪ Stable molecule ▪ Cell nuclei ▪ Ribonucleic Acid (RNA): ▪ Short-lived molecule ▪ Involved in decoding information from DNA into instructions for protein assembly, as well as assembling the protein Chapter 2 - Chemicals of Life 137  I. NUCLEIC ACIDS HHP:3550 NUCLEOTIDES ❑ Both DNA and RNA are made up of repeating units called NUCLEOTIDES – Nucleotide = Sugar + Phosphate + Base ▪ Identify each component in the figures below – Nucleotides connected by sugar-phosphate bonds Chapter 2 - Chemicals of Life 138  I. NUCLEIC ACIDS HHP:3550 NUCLEOTIDES (PURINES VS. PYRIMIDINES) ❑ Specific nucleotides determined by the base – 5 different bases ▪ Purines (double rings) – Adenine (DNA & RNA) – Guanine (DNA & RNA) – “Pure As Gold” ▪ Pyrimidines (single ring) – Cytosine (DNA & RNA) – Thymine (only DNA) – Uracil (only RNA) – “C-U-T the Py” Chapter 2 - Chemicals of Life 139  II. DEOXYRIBONUCLEIC ACID (DNA) HHP:3550 DNA CHARACTERISTICS (SUGARS AND BASES) ❑DNA Sugar = deoxyribose ❑ DNA Bases: – Purines: A and G – Pyrimidines: C and T Chapter 2 - Chemicals of Life 140  II. DEOXYRIBONUCLEIC ACID (DNA) HHP:3550 DNA CHARACTERISTICS (DOUBLE HELIX) ❑ DNA exists as 2 strands of nucleotides coiled into a double helix How are the 2 strands held together? Chapter 2 - Chemicals of Life 141  II. DEOXYRIBONUCLEIC ACID (DNA) HHP:3550 DNA CHARACTERISTICS (DOUBLE HELIX) DNA exists as 2 strands of nucleotides coiled into a double helix What are the advantages of this double- helix configuration? Chapter 2 - Chemicals of Life 142  II. DEOXYRIBONUCLEIC ACID (DNA) HHP:3550 DNA CHARACTERISTICS (DOUBLE HELIX) ❑ DNA exists as 2 strands of nucleotides coiled into a double helix When must the double-helix be separated? Chapter 2 - Chemicals of Life 143  III. RIBONUCLEIC ACID (RNA) HHP:3550 RNA CHARACTERISTICS (SUGAR AND BASES) ❑RNA Sugar = Ribose ❑ RNA Bases: – Purines: A and G – Pyrimidines: U (replaces T) and C Chapter 2 - Chemicals of Life 144  III. RIBONUCLEIC ACID (RNA) HHP:3550 RNA CHARACTERISTICS (SINGLE STRAND) ❑ RNA exists as a single strand Can base-pair with itself or other molecules of DNA or RNA – Not as stable as DNA ▪ Why is this a good thing? Chapter 2 - Chemicals of Life 145  I. NUCLEIC ACIDS HHP:3550 SUMMARY ❑ Living organisms are comprised of carbon- containing molecules ❑ 4 categories of macromolecules in the human body 1. Carbohydrates 2. Lipids 3. Proteins 4. Nucleic acids Chapter 2 - Chemicals of Life 146  SUMMARY - TERMINOLOGY HHP:3550 Nucleotide DNA RNA Chapter 2 - Chemicals of Life 147  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Identify the structural components of nucleotides 2. Compare and contrast DNA and RNA, considering the sugar unit, the bases associated with each molecule, and their overall configurations 3. Explain how the strands of DNA held together, and describe the functional consequences of the double-helix configuration Chapter 2 - Chemicals of Life 148  HHP:3550 Human Physiology CHAPTER 3 CELL STRUCTURE Overview of Eukaryotic Cells  CHAPTER 3 HHP:3550 Week 2 Cell Structure Protein Synthesis, Degradation, and Secretion Interactions between Proteins and Ligands Chemical Reactions and Enzymes Week 3 Metabolic Pathways Chapter 3 150  LECTURE OUTLINE HHP:3550 I. Overview of Eukaryotic Cells II. Plasma Membrane Characteristics III. Cellular Organelles Chapter 3 151  I. OVERVIEW OF EUKARYOTIC CELLS HHP:3550 ❑ The functional unit of living organisms is the cell – Multicellular organisms are made of eukaryotic cells ▪ Nucleus ▪ Organelles ▪ Compart- mentalization: plasma membranes – Prokaryotic cells lack these structures Chapter 3 152  I. OVERVIEW OF EUKARYOTIC CELLS HHP:3550 ❑ General Principles of Physiology: Structure is a determinant of function – coevolved – All of the cells below are found in the human body share many of the same intracellular structures adaptations of cellular structure to meet functional needs Chapter 3 153  I. OVERVIEW OF EUKARYOTIC CELLS HHP:3550 ❑ The plasma membrane surrounding the cell is the cell membrane – Organelles: membrane- bound structures that perform specific functions – Cytoplasm: everything inside cell membrane except the nucleus – Cytosol: fluid inside the cell membrane but outside of the organelles Chapter 3 154  I. OVERVIEW OF EUKARYOTIC CELLS HHP:3550 ❑ Plasma Membrane Functions 1. Selective barrier: surrounding whole cell, organelles, nucleus ▪ Compartmentalization ▪ Movement of molecules between compartments – Selectivity – Regulation Chapter 3 155  I. OVERVIEW OF EUKARYOTIC CELLS HHP:3550 ❑ Plasma Membrane Functions 2. Sensors of chemical messengers, cell signaling ▪ Remember the 4 intercellular signaling molecules? Chapter 3 156  I. OVERVIEW OF EUKARYOTIC CELLS HHP:3550 ❑ Plasma Membrane Functions 3. Cellular support: anchors cells to adjacent cells and to extracellular matrix (ECM) ▪ Glycoproteins in ECM bind to proteins in plasma membrane ▪ Provide sites for transmission of forces Chapter 3 157  II. PLASMA MEMBRANE CHARACTERISTICS HHP:3550 ❑ Plasma Membrane Structure – Double layer of phospholipids ▪ What is special about phospholipids? ▪ Where are they in this figure? ▪ Function? Chapter 3 158  II. PLASMA MEMBRANE CHARACTERISTICS HHP:3550 ❑ Plasma Membrane Structure – Few chemical bonds link the phospholipids ▪ Fluid structure ▪ Cholesterol adds stability to cell membrane – Where in this figure? Chapter 3 159  II. PLASMA MEMBRANE CHARACTERISTICS HHP:3550 ❑ Proteins in the Cell Membrane 1. Integral Proteins: embedded within cell membrane ▪ Amphipathic ▪ Transmembrane proteins: can form channels, transmit chemical signals from ECF → ICF Chapter 3 160  II. PLASMA MEMBRANE CHARACTERISTICS HHP:3550 ❑ Proteins in the Cell Membrane 2. Peripheral Proteins: attached to inside or outside ▪ Functions: enzyme activity, cell shape and motility Chapter 3 161  II. PLASMA MEMBRANE CHARACTERISTICS HHP:3550 ❑ Proteins in the Cell Membrane 3. Glycocalyx: glycoproteins ▪ Function: cell recognition Chapter 3 162  II. PLASMA MEMBRANE CHARACTERISTICS HHP:3550 What types of connections hold cells together to form tissues? Do these connections have any other functions? Chapter 3 163  II. PLASMA MEMBRANE CHARACTERISTICS HHP:3550 ❑ Cell Membrane Junctions – Physical connections between cells 1. Desmosome ▪ Membranes of adjacent cells linked by strong fibers in isolated spots ▪ Holds cells firmly together, structural support ▪ Important in areas subjected to stretch – Example: skin Chapter 3 164  II. PLASMA MEMBRANE CHARACTERISTICS HHP:3550 ❑ Cell Membrane Junctions 2. Tight Junctions ▪ Membranes joined with no space between them, connections go all the way around cell ▪ Restricts molecular diffusion between cells – Water, small ions may still pass through ▪ Paracellular vs. transcellular pathways Chapter 3 165  II. PLASMA MEMBRANE CHARACTERISTICS HHP:3550 ❑ Cell Membrane Junctions 3. Gap Junctions ▪ Protein channels link cytosol of adjacent cells ▪ Allows small molecules and ions to pass between cells – Examples: Na+, K+ ▪ Allows rapid electrical communication between cells Chapter 3 166  III. CELLULAR ORGANELLES HHP:3550 What are the specific intracellular structures associated with eukaryotic cells? What do they “do”? Chapter 3 167  III. CELLULAR ORGANELLES HHP:3550 ❑ What Are Cellular Organelles? – Plasma membrane-bound structures that perform specific cellular functions – Learning Objective: provide a 3–5-word description of the major function accomplished by each organelle Chapter 3 168  III. CELLULAR ORGANELLES HHP:3550 1. Nucleus: “Command Center” ❑ Fun Facts: – Largest cellular organelle – Most cells contain one nucleus – Exceptions: ▪ Skeletal muscle cells ▪ Red blood cells Chapter 3 169  III. CELLULAR ORGANELLES HHP:3550 1. Nucleus – Functions: ▪ Stores genetic information in the form of DNA ▪ “Blueprints” for protein synthesis – Structures: ▪ Nucleolus: site of ribosomal RNA synthesis ▪ Chromatin: DNA ▪ Nuclear envelope, nuclear pores: allow passage of mRNA into cytoplasm Chapter 3 170  III. CELLULAR ORGANELLES HHP:3550 2. Ribosomes – Function: protein assembly by connecting amino acids ▪ Fun Fact: up to 10 million per cell 1. Free ribosomes release proteins into cytosol 2. Bound ribosomes: attached to endoplasmic reticulum, release proteins into this organelle Chapter 3 171  III. CELLULAR ORGANELLES HHP:3550 3. Endoplasmic Reticulum (ER) ▪ Large, continuous space enclosed by membranes 1. Rough ER: contain ribosomes, involved in packaging of proteins 2. Smooth ER: lipid synthesis, Ca2+ handling Chapter 3 172  III. CELLULAR ORGANELLES HHP:3550 4. Golgi Apparatus – Series of flattened, membranous sacs – Function: protein modification – Also packages proteins into vesicles 1. Intracellular transport 2. Secretory vesicles: fuse with cell membrane → release contents Chapter 3 173  III. CELLULAR ORGANELLES HHP:3550 5. Mitochondria – Produce most of the cell’s energy (ATP) – “Powerhouse of the cell” 1. Inner, outer mitochondrial membranes 2. Mitochondrial matrix ▪ Consume O2 ▪ Produce CO2, heat, and H20 – Fun Fact: in response to endurance exercise training, mitochondria grow in size & number Chapter 3 174  III. CELLULAR ORGANELLES HHP:3550 6. Lysosomes – Contain acidic fluid and digestive enzymes – Break down bacteria, damaged cells, and cellular debris Chapter 3 175  III. CELLULAR ORGANELLES HHP:3550 7. Peroxisomes – Contain enzymes that oxidize organic molecules ▪ Hydrogen peroxide (H2O2)– a free radical ▪ Lipids, alcohol, some toxins Chapter 3 176  III. CELLULAR ORGANELLES HHP:3550 8. Cytoskeleton – Generally proteins – Not a membrane-enclosed organelle, but important for overall cell function 1. Helps cell maintain and change shape 2. Produce cell movements 3. Important in DNA segregation 3 types based upon size: during cell division Microfilament (actin) Intermediate filament Microtubules Chapter 3 177  SUMMARY - TERMINOLOGY HHP:3550 ❑ Structures Associated with Eukaryotic Cells: cell membrane (plasma membrane, plasmalemma) nucleus organelle cytoplasm, cytosol extracellular matrix integral protein peripheral protein glycocalyx glycoproteins desmosome tight junction gap junction paracellular pathway transcellular pathway endoplasmic reticulum (rough, smooth) vesicle mitochondria ribosomes Peroxisomes cytoskeleton Golgi apparatus Lysosomes 1 Chapter 3 178 7  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Define the terms plasma membrane, organelle, cytoplasm, and cytosol 2. List three functions of the cell membrane 3. Describe the structure of the cell membrane, including the roles of phospholipids, cholesterol, and integral and peripheral membrane proteins 4. Review what the glycocalyx is, where it is located relative to cells, and its primary function 5. Describe how the amphipathic nature of phospholipids results in the formation of a fluid bilayer Chapter 3 179  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 6. Describe the function and structure of desmosomes, tight junctions, gap junctions as specialized membrane junctions that join adjacent cells 7. Describe the basic structures and functions of the following cellular organelles: nucleus, ribosomes, rough endoplasmic reticulum, smooth endoplasmic reticulum, Golgi apparatus, mitochondria, lysosomes, peroxisomes, and the cytoskeleton Chapter 3 180  HHP:3550 Human Physiology CHAPTER 3 WHAT DO PROTEINS DO? Protein Synthesis: Transcription and Translation  LECTURE OUTLINE HHP:3550 I. Genetic Code II. Protein Synthesis A. Transcription B. Translation C. Mutation III. Summary Chapter 3 182  I. GENETIC CODE HHP:3550 REVIEW ❑ Remember: Proteins are involved in all physiological processes ❑ How are proteins made? – The genetic code provides the instructions for protein synthesis – Genetic code stored in DNA – Code transferred from DNA → RNA (transcription) – Code within RNA used to assemble proteins (translation) Chapter 3 183  I. GENETIC CODE HHP:3550 REVIEW ❑ Remember: – DNA/RNA are nucleic acid polymers made up of repeating nucleotides – A nucleotide = sugar + phosphate + base – Specific base determines the nucleotide ▪ DNA Bases? ▪ RNA Bases? – The specific number and order of amino acids in a protein is encoded within the sequence of nucleotides in DNA and RNA Chapter 3 184  I. GENETIC CODE HHP:3550 TERMINOLOGY ❑ Genome: all genetic information coded in the DNA of a cell – Human Genome contains ~ 3 billion nucleotides and ~20,000 genes found within 46 chromosomes (23 pairs) ❑ Chromosome: a single DNA molecule and its associated packaging proteins (histones) Chapter 3 185  I. GENETIC CODE HHP:3550 TERMINOLOGY ❑ Gene: a sequence of DNA nucleotides within a chromosome that codes for a single, specific protein ❑ Proteome: the specific proteins produced by a given cell at a given time ‒ How many genes does a human cell have? ‒ How many proteins within a typical human cell proteome? Chapter 3 186  I. GENETIC CODE HHP:3550 TERMINOLOGY ❑ Triplet: sequence of 3 DNA nucleotides within a gene that codes for a specific amino acid – Most amino acids associated with >1 triplet ▪ How many possible triplets? ▪ How many amino acids? – 3 triplet sequences serve as “stop” signals Chapter 3 187  I. GENETIC CODE HHP:3550 SUMMARY (ANALOGY) ❑ If the human genome is a cookbook… – Each recipe would be a. – Recipes would be described with words, that is ____. – These words would be written with letters, that is _______. – All of the food that a given kitchen makes using the cookbook would correspond to the. Chapter 3 188  II. PROTEIN SYNTHESIS HHP:3550 OVERVIEW ❑ Now that we understand the genetic code, we will discuss the specifics of … – How the code gets transferred to a temporary messenger nucleic acid (Transcription) – How that temporary messenger is used to assemble a protein (Translation) – How the assembled protein can be modified post- translation – What happens if errors are introduced into the genetic code (Mutations) Chapter 3 189  II. PROTEIN SYNTHESIS HHP:3550 OVERVIEW ❑ TRANSCRIPTION = copying directions for how to make a protein FROM a gene within the DNA TO a temporary “messenger” nucleic acid – Temporary messenger = Messenger RNA (mRNA) ▪ Information from a single gene for a single protein ▪ Information carried to cytoplasm Chapter 3 190  II. PROTEIN SYNTHESIS HHP:3550 TRANSCRIPTION ❑ Transcription: primary RNA transcript synthesis – RNA polymerase binds to promoter sequence on gene, leading to… ▪ DNA strands separating ▪ Assembling of free nucleotides to form RNA transcript Chapter 3 191  II. PROTEIN SYNTHESIS HHP:3550 TRANSCRIPTION ❑ Transcription: primary RNA transcript synthesis (cont.) – When synthesizing RNA transcript, specificity of base-pairing maintains code: ▪ A→U ▪ T→A ▪ C→G ▪ G→C ▪ 1 DNA triplet codes for a specific RNA codon Chapter 3 192  II. PROTEIN SYNTHESIS HHP:3550 TRANSCRIPTION ❑ Transcription: splicing primary RNA transcript – Once primary RNA transcript (aka pre mRNA) is completed, must be processed by Spliceosomes – Exons are kept in ▪ EXpressed RegiONS – Introns are spliced out ▪ 98.5% of code consists of introns – Final product is mRNA, which travels to cytoplasm to be translated Chapter 3 193  II. PROTEIN SYNTHESIS HHP:3550 TRANSLATION ❑ TRANSLATION is the process by which polypeptides are assembled in the cytoplasm from the instructions encoded within the mRNA – Assembly requires… ▪ Ribosomes ▪ Transfer RNA (tRNA) ▪ Initiation factors … which will be discussed in turn Chapter 3 194  II. PROTEIN SYNTHESIS HHP:3550 TRANSLATION ❑ Ribosomes – Within cytoplasm Ribosomes are the organelle responsible for assembling the polypeptides ▪ Ribosomes can be “free”, or bound to RER ▪ 2 subunits: 1 large, 1 small Chapter 3 195  II. PROTEIN SYNTHESIS HHP:3550 TRANSLATION ❑ Transfer RNA (tRNA) – Transfer RNA (tRNA) links mRNA to a specific amino acid (AA) for assembly ▪ tRNA binds covalently to a specific AA ▪ tRNA contains an anticodon to bind to the mRNA codon Chapter 3 196  II. PROTEIN SYNTHESIS HHP:3550 TRANSLATION ❑ Protein Assembly (Initiation) – The first step of protein assembly, Initiation, occurs when tRNA containing AA methionine binds to small sub-unit – Large sub-unit then binds – Slowest of 3 steps – Initiation factors required Chapter 3 197  II. PROTEIN SYNTHESIS HHP:3550 TRANSLATION ❑ Protein Assembly (Elongation) – Following initiation, Elongation occurs – New tRNA with linked AA moves into place – New AA linked to existing polypeptide chain via peptide bond – 2 to 3 AA added per second Chapter 3 198  II. PROTEIN SYNTHESIS HHP:3550 TRANSLATION ❑ Protein Assembly (Termination) – When ribosome reaches “stop” codon, protein assembly Termination occurs – Polypeptide chain is released – Ribosome disassembles – mRNA persists for a time, can be translated multiple times (even simultaneously) Chapter 3 199  II. PROTEIN SYNTHESIS HHP:3550 TRANSLATION ❑ Post-Assembly Modification – Polypeptides can be cut to form multiple, smaller proteins – Lipids or carbohydrates can be covalently bonded to the protein to affect its stability/function Chapter 3 200  II. PROTEIN SYNTHESIS HHP:3550 SUMMARY OF TRANSLATION & TRANSCRIPTION ❑ Watch CONNECT Video: “How Translation Works” ❑ Review Table 3.2 in text Chapter 3 201  II. PROTEIN SYNTHESIS HHP:3550 MUTATION ❑ Mutation: any change in nucleotide sequence within DNA – Caused by breaking of DNA with subsequent errors in reformation – An element that increases the rate of mutations is known as a Mutagen Chapter 3 202  II. PROTEIN SYNTHESIS HHP:3550 MUTATION ❑ Mutation: any change in nucleotide sequence in DNA – Change in nucleotides can potentially cause a change in the assembled protein 1° structure – Leads to change in shape, and in turn potentially a change in cellular (and organismal) function – Read Clinical Case Study on p. 42 Chapter 3 203  SUMMARY - TERMINOLOGY HHP:3550 ❑ Terminology associated with the genetic code: genome, chromosome, gene, triplet, proteome ❑ Structures/molecules associated with proteins: triplet, mRNA, RNA polymerase, promoter sequence, codon, spliceosomes, exons, introns, tRNA, anticodon ❑ Processes related to protein synthesis: transcription, translation, initiation, elongation, termination, mutation Chapter 3 204  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Describe the relationship between the genetic code and the synthesis of proteins 2. Define the terms: genome, chromosome, gene, triplet, and proteome 3. Discuss transcription of DNA to mRNA, the factors that influence it, and how this process fits into protein synthesis; define introns, exons, and spliceosomes 4. Discuss translation of mRNA into a protein by the ribosomes; understand the role of tRNA, and the relationship between a DNA triplet, an mRNA codon, and a tRNA anticodon 5. Explain how translation is initiated and terminated Chapter 3 205  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 6. Know the slowest step of translation, and how this step is regulated 7. Describe post-translational modifications that can be made to proteins 8. Discuss how the location of protein assembly differs between proteins destined for the cytoplasm and those destined for secretion 9. Detail the regulation of protein synthesis, discussing regulation of both transcription and translation 10. Discuss how protein degradation rates can influence cellular concentrations of a protein, and factors that influence degradation Chapter 3 206  SUMMARY – CHALLENGE QUESTION HHP:3550 – Starting with the DNA triplet C-A-T, determine: ▪ the corresponding mRNA codon ▪ the tRNA anti-codon ▪ the amino acid Chapter 3 207  HHP:3550 Human Physiology CHAPTER 3 WHAT DO PROTEINS DO? Protein Regulation & Secretion  LECTURE OUTLINE HHP:3550 I. Regulation of Protein Content A. Regulation of Synthesis B. Protein Degradation II. Protein Secretion III. Summary Chapter 3 209  I. REGULATION OF PROTEIN CONTENT HHP:3550 REGULATION OF SYNTHESIS (TRANSCRIPTION) ❑ Big-Picture View of Transcription Regulation – Only small # of genes are transcribed in any cell (How many?) – Some genes continuously transcribed (Genes involved with what types of processes?) – Transcription of most genes can be turned on or off, or up-regulated or down-regulated, in response to internal or external signals Chapter 3 210  I. REGULATION OF PROTEIN CONTENT HHP:3550 REGULATION OF SYNTHESIS (TRANSCRIPTION) ❑ Transcription of most genes is increased or decreased by transcription factors – How do transcription factors act? Chapter 3 211  I. REGULATION OF PROTEIN CONTENT HHP:3550 REGULATION OF SYNTHESIS (TRANSLATION) ❑ Once a gene is transcribed into an mRNA, which factors influence how much protein will be produced? – RNase activity and mRNA stability – Initiation factors (and elongation factors) – # of Ribosomes Chapter 3 212  I. REGULATION OF PROTEIN CONTENT HHP:3550 PROTEIN DEGRADATION ❑ Protein Degradation: The Breakdown of Proteins – Protein concentration is balance between synthesis and degradation Cardiovasres.oxfordjournal.org Chapter 3 213  I. REGULATION OF PROTEIN CONTENT HHP:3550 PROTEIN DEGRADATION ❑ Protein Degradation: The Breakdown of Proteins – Role of ubiquitin and proteasomes – Other protein chaperones (HSPs) LifeSensors Chapter 3 214  I. REGULATION OF PROTEIN CONTENT HHP:3550 SUMMARY When your body is exposed to strength training and protein feeding, there is an increase in skeletal muscle protein content. Applying the concepts just discussed, what are the various ways that this increase in muscle protein could be brought about? Above and beyond: Of these potential points of regulation, which appear to be most influential based upon research? Chapter 3 215  II. PROTEIN SECRETION HHP:3550 FREE RIBOSOMES VS. RER Chapter 3 216  II. PROTEIN SECRETION ASSEMBLY, MODIFICATION, AND HHP:3550 PACKAGING ❑ Ribosome synthesizing ❑ protein to be secreted binds to RER early in translation ❑ Assembly completed within lumen of RER ❑ The protein undergoes modification by the Golgi apparatus ❑ The Golgi apparatus packages proteins into membrane-bound vesicles for secretion from cell Chapter 3 217  SUMMARY - TERMINOLOGY HHP:3550 Transcription factor Proteasome Ubiquitin Rough Endoplasmic Reticulum Golgi Apparatus Vesicle Chapter 3 218  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Detail the regulation of protein synthesis, discussing regulation of both transcription and translation 2. Discuss how protein degradation rates can influence cellular concentrations of a protein, and factors that influence degradation 3. Discuss how the location of protein assembly differs between proteins destined for the cytoplasm and those destined for secretion Chapter 3 219  HHP:3550 Human Physiology CHAPTER 3 WHAT DO PROTEINS DO? Protein-Ligand Binding  LECTURE OUTLINE HHP:3550 I. Protein-Ligand Binding Overview II. Protein-Ligand Binding Characteristics III. Regulation of Protein-Ligand Binding IV. Summary Chapter 3 221  I. PROTEIN-LIGAND BINDING OVERVIEW HHP:3550 IMPORTANCE ❑ Importance of protein binding to molecules/ions – Proteins binding to other molecules forms the basis for a wide variety of protein functions ▪ Proteins as enzymes ▪ Proteins as signaling molecules and receptors ▪ Proteins as transporters ▪ Proteins as motors within our bodies ▪ Proteins as part of the immune system Chapter 3 222  I. PROTEIN-LIGAND BINDING OVERVIEW HHP:3550 TERMINOLOGY ❑ Ligand: any molecule/ion that binds reversibly to a protein by intermolecular forces 1. Electrical attraction from opposite charges 2. Hydrophobic forces between non- polar regions ❑ Binding Site: the location on the protein to which the ligand binds Chapter 3 223  I. PROTEIN-LIGAND BINDING OVERVIEW HHP:3550 TERMINOLOGY ❑ Binding site (cont.) – Each protein may contain multiple binding sites for… ▪ Same ligand ▪ Different ligands – Ligand-protein binding leads to change in protein function ▪ Activation or inhibition ▪ Ligand as a signaling molecule Chapter 3 224  II. PROTEIN-LIGAND BINDING CHARACTERISTICS OVERVIEW HHP:3550 ❑ Binding Site Characteristics: factors that influence ligand-protein interactions – All of the types of protein-ligand binding relationships we will discuss throughout the course possess the following characteristics… ▪ Specificity ▪ Affinity ▪ Saturation ▪ Competition …we will discuss these in turn Chapter 3 225  II. PROTEIN-LIGAND BINDING CHARACTERISTICS SPECIFICITY HHP:3550 1. Chemical Specificity – Binding site selectively binds specific ligands ▪ Based upon complementary shape ▪ Different degrees of specificity exist (see figure) ▪ Which protein has greater specificity? Chapter 3 226  II. PROTEIN-LIGAND BINDING CHARACTERISTICS AFFINITY HHP:3550 2. Affinity: the strength of a ligand-protein binding – Tight binding = high affinity – Weak binding = low affinity – Related to both the shape and the electrical charge of the interacting molecules Chapter 3 227  II. PROTEIN-LIGAND BINDING CHARACTERISTICS SATURATION (EFFECT OF CONCENTRATION) HHP:3550 3. Saturation: fraction of total binding sites occupied at any given time – Depends upon: 1) Ligand concentration, 2) Affinity Saturation Curve: Relationship between ligand concentration and % saturation Chapter 3 228  II. PROTEIN-LIGAND BINDING CHARACTERISTICS SATURATION (EFFECT OF CONCENTRATION) HHP:3550 3. Saturation (cont.) – Depends upon: 1) Ligand concentration, 2) Affinity If binding of ligand elicits physiological effect, what change would be seen as ligand concentration increases from Point B to Point D? Point D to Point E? Chapter 3 229  II. PROTEIN-LIGAND BINDING CHARACTERISTICS SATURATION (EFFECT OF AFFINITY) HHP:3550 3. Saturation (cont.) – Depends upon: 1) Ligand concentration, 2) Affinity Note effect of affinity on the saturation curves shown Which Protein has the higher affinity for the ligand? Chapter 3 230  II. PROTEIN-LIGAND BINDING CHARACTERISTICS COMPETITION HHP:3550 4. Competition: occurs when two ligands can bind to the same protein ▪ Ligands A and B can both bind to the same binding site on Protein X ▪ How will the saturation of Protein X with Ligand A be affected by a rising concentration of Ligand B? Chapter 3 231  III. REGULATION OF PROTEIN-LIGAND BINDING OVERVIEW HHP:3550 ❑ How is protein activity regulated? 1. Regulate the amount of protein ▪ How? 2. Regulate the shape of protein ▪ How? – Allosteric modulation – Covalent modulation Chapter 3 232  III. REGULATION OF PROTEIN-LIGAND BINDING ALLOSTERIC MODULATION HHP:3550 ❑ Allosteric Modulation: non-covalent binding of a modulator ligand to a regulatory site, which changes the shape/activity of the functional site – What changes can occur? Chapter 3 233  III. REGULATION OF PROTEIN-LIGAND BINDING ALLOSTERIC MODULATION (COOPERATIVITY) HHP:3550 ❑ Allosteric Modulation – If protein has multiple functional sites that influence each other, this is known as cooperativity ▪ Example: hemoglobin Chapter 3 234  III. REGULATION OF PROTEIN-LIGAND BINDING COVALENT MODULATION HHP:3550 ❑ Covalent Modulation: covalent bonding of a charged chemical group (usually phosphate) to a protein → phosphorylation ▪ Enzyme that adds a phosphate = kinase ▪ Enzyme that removes a phosphate = phosphatase Chapter 3 235  SUMMARY - TERMINOLOGY HHP:3550 ❑ Protein-ligand interactions: ligand, binding site, specificity, affinity, saturation, competition ❑ Binding site regulation: allosteric modulation, covalent modulation, modulator ligand, regulatory site, functional site, cooperativity, kinase, phosphatase Chapter 3 236  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to… 1. Define binding site and ligand, and describe the forces through which they interact 2. Define specificity and affinity and know the factors that affect each 3. Define saturation and describe the factors that affect it 4. Draw a saturation curve; know what goes on each axis, the general shape of the relationship, the physiological meaning of the relationship, and how the curve would be affected by affinity changes 5. Draw the effect of a competitor on the saturation curve of a given protein-ligand binding relationship Chapter 3 237  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ You should be able to … 6. Describe how protein activity can be affected by both protein concentration as well as protein shape 7. Define allosteric modulation, regulatory site, functional site, and cooperativity 7. Define covalent modulation, and understand the roles played by kinases and phosphatases 8. Understand the differences in complexity between allosteric and covalent modulation, and the significance of those differences Chapter 3 238  SUMMARY – LEARNING ACTIVITIES HHP:3550 ❑ Challenge Questions 1. Protein A has a binding site with a positive-charged ionic region. Ligand A and B both have shapes complementary to the binding site. The binding region of Ligand A is negatively- charged, and Ligand B is polar. Draw saturation curves for each ligand. 2. The hormone leptin is produced by adipose tissue and causes an increase in energy expenditure and a decrease in appetite. In cases of chronic obesity, the body’s response decreases substantially. Suggest a reason for this in terms of properties of protein binding sites. 3. If ligands A and B can both bind to the same protein, which factor/s will determine which ligand is bound to a greater extent? Chapter 3 239  HHP:3550 Human Physiology CHAPTER 3 WHAT DO PROTEINS DO? Chemical Reactions and Enzymes  LECTURE OUTLINE HHP:3550 I. Chemical Reactions II. Overview of Enzymes III. Regulation of Enzyme-Mediated Reactions IV. Summary Chapter 3 241  I. CHEMICAL REACTIONS HHP:3550 WHAT IS METABOLISM? ❑ Metabolism: all of the chemical reactions that occur