Ch4B Energy and Metabolism PDF

Ch4B Energy and Metabolism Learning Objective 1: Describe types of energy AND how enzymes are categorized. Metabolism is the process by which our cells convert food into energy. Metabolism involves a series of chemical reactions catalyzed (triggered) by enzymes that use energy. Essentially our cells...

Ch4B Energy and Metabolism Learning Objective 1: Describe types of energy AND how enzymes are categorized. Metabolism is the process by which our cells convert food into energy. Metabolism involves a series of chemical reactions catalyzed (triggered) by enzymes that use energy. Essentially our cells use energy to make more energy What is energy and why do we need it? Energy is the capacity to do work. In our cells, energy is known as ATP (adenosine triphosphate) Types of Energy : Chemical work is making and breaking of chemical bonds − e.g., forming pepƟde bonds in protein Transport work involves moving ions and molecules through biological membranes− can create concentraƟon gradients (membrane physiology) Mechanical work involves movement − e.g., organelles, muscle contracƟons Chemical Reactions AND Energy Our cells perform chemical reactions all the time (besides metabolism). Energy is needed to perform chemical reactions. Gibbs free energy (ΔG) is the amount of energy that can be used to do work. 1. Exergonic reactions produce a net release of energy (spontaneous)( Negative free energy) 2. Endergonic reactions require a net input of energy (Positive Free Energy) Exergonic reactions can be used to “drive” endergonic reactions. Exergonic Reaction The product energy is lower than reactive energy. Start with High reactant (Sale-Exit) Endergonic Reaction : ATP is the reactant , Energy is added. the product energy is higher (Entra-Ender) Regardless if its exergonic or endergonic reaction, all reaction has to go over the “HUMP” The Humps is called Activation Energy In general, chemical reactions are slow because of the activation energy. So how can the cells in our body make chemical reactions go quickly? This is where enzymes come into play. Enzymes are biological catalysts. Remember enzymes are proteins. Enzymes typically end with the suffix – ase. A catalyst is when the activation energy of a chemical reaction is lowered. Substrate(s) are substances that bind to enzymes. Enzymes lower the activation energy of a reaction − put substrates in posiƟon to react Increasing the enzyme concentration will speed up the rate of a reaction − must have free substrate available (will come up in a liƩle) Increasing the substrate concentration will speed up the rate of a reaction − must have free enzyme available − saturaƟon occurs when all enzyme are bound by substrate (will come up in a little) Catalytic Cycle of Enzyme 1.- The enzyme is available with an empty Active Site 2.- The substrate enters the active site, which enfolds the substrate with an induced fit 3.- The substrate is converted to products (2) 4.- The products are release ( 2 products ) Enzyme Terms : Active site is region where substrate binds and undergoes a reaction − binding site and catalyƟc site Cofactor is substance that is required for an enzyme to be active − metallic ion (Ca2+, Mg2+, Fe2+) Coenzymes are organic cofactors that influence enzyme activity − many are vitamins Substrate binding depends on specificity and Affinity Specificity is ability of an enzyme to bind to a certain substrate − may bind to one substrate or a group of related substrates Affinity is degree to which an enzyme is attracted to a substrate − ↑ affinity = more likely to bind − influenced by many factors How can we model affinity? We need to use the enzyme kinetics graph. Kinetics is the study of chemical reaction rates (velocity/speed of chemical reactions). How can we model affinity? Y axis = reaction rate (Vo). X axis =concentration of available substrates for enzymes. This graph assumes you are testing a constant concentration of enzymes added WITH differing concentrations of substrate. Vmax occurs when all enzymes are saturated (all enzymes are filled by substrates). Vmax/2 is also known as the Km. Km measures binding affinity. Low Km means higher affinity for the substrate to an enzyme’s active site. High Km means lower affinity for the substrate to an enzyme’s active site Inhibitors affect enzyme’s kinetics There are also inhibitors that can affect an enzyme’s kinetics. Drugs also can be inhibitors as well. Competitive inhibitors compete with the substrate of enzymes for that enzyme’s active site. -an enzyme’s Vmax does not change BUT you need to increase Km to get to Vmax -Penicillin and other antibiotics are examples Noncompetitive inhibitors do NOT compete with the substrate of an enzyme at the active site BUT this inhibitor will bind at other sites and slow down enzyme activity -enzyme’s Vmax is lowered BUT Km stays the same - Cyanide is an example Allosteric binding is the process of an effector binding to an enzyme to modify its activity. Allosteric binding means the shape of the enzyme changes after an effector substrate binds to it. Allosteric regulation/binding Allosteric binding , broadly speaking, is just any form of regulation where the regulatory molecule (an activator or inhibitor) binds to an enzyme someplace other than the active site. The place where the regulator binds is called the allosteric site. CH4B “Describe Glycolysis The first step of Metabolism “ Glycolysis (Requires energy) converts one glucose into two pyruvates Takes place in CYTOSOL Does not required Oxygen 10 steps divide into two phases Glycolysis is a 2 phase process: Energy requiring Phase : split into 2 (3 carbon Sugars) Add two phosphates Add two ATP. Energy-Releasing Phase : Converts the 2 (3 carbon Sugars) into two Pyruvates Occurs twice (one for each sugar) Overview of Glycolysis Glycolysis (per glucose) Input: 1 glucose, 2 ATP Output: 2 pyruvate Net Energy Gain: 4 ATP , 2 NADH Chapter 4B Objective 3 :Describe Pyruvate Oxidation Reminder : 2 pyruvates are released after Glycolysis Pyruvate oxidation is the 2nd step of Metabolism Why does Pyruvate oxidation happen? A Pyruvate enters Aerobic Respiration Where does Pyruvate oxidation Happens: Mitochondrial Matrix What is the product of Pyruvate oxidation? Steps of Pyruvate Oxidation: 1.- A carboxyl group is remove releasing CO2 2.-NAD+ gets reduced to NADH 3.- Coenzyme A joins the remaining two carbon molecule to form: Acetyl-Coa Pyruvate oxidation Input and Output Input : 2 pyruvates + 2 coenzyme A Output: 2 Acetyl-Coa and CO2 Gain: 2 NADH Citric Acid Cycle (removing and adding carbons) Enters Objective 4: Citric Acid Cycle Citric acid Cycle also known as TCA or Krebs Cycle is the 3rd step of Metabolism that doesn't have a beginning or end. What does the citric acid cycle consist of? Reactions that harvest the energy of Where does the Citric acid cycle take place? Mitochondrial Matrix How many Acetyl-Coa are produced for each Glucose : How many times does the citric acid occurs: 2 2 Steps of Citric Acid cycle 1.- 2 Acetyl-coa joins a 4 carbon molecule called Oxaloacetate and form 6 carbon Citrate releasing COA ⚫ ⚫⚫⚫⚫⚫⚫) 2.-CO2 is release to form a 5 carbon called Alpha Ketoglutarate(⚫⚫⚫⚫⚫) In this step NAD+ is produce and CO2 is released ACETYL-COA ACETYL-COA ⬤ + Oxaloacetate ⚫⚫⚫⚫ = Citrate ( 3.- CO2 is released and COA is added to form a 4- carbon Succinyl-COA 4.- Coenzyme A is removed to form Succinate to make ATP 5.- Succinate forms to Oxaloacetate by making FADH2 and NADH. Input: 2 acetyl-Coa Output : 4 CO2 Gain: 2 ATP 6 NADH 2 FADH2 NADH and FADH carry electrons to the next step to drive ATP synthesis ***Any Molecule can enter into the citric acid cycle Objective 5: Oxidative Phosphorylation. Oxidative Phosphorylation is the last step of metabolism. Oxidative Phosphorylation transfers electrons from NADH and FADH2 to O2 Oxidative phosphorylation happens at Inner Mitochondrial Membrane Oxidative phosphorylation is a 2 step process : 1. Electron transport chain 2. Chemiosmosis 1.-Electron transport chain is a series of electron transporters that pass electrons via redox reactions. Using ATP to create H+ gradients. You will need Water. You need NADH , FADH2 and O2 to finish this electron movement called the Electron transport chain. Electron transport chain has two major functions: − regenerates NAD+ and FAD − creates a H+ gradient for chemiosmosis to occur. Intermembrane Space (inside) = High concentration of H+ Mitochondrial Matrix (outside) = Low concentration of H+ Oxidative phosphorylation:Electron transport chain 1. NADH donates to complex I; and FADH2 donates to complex II − NAD+ and FAD are reformed 2. Energy from electron transfer is used to create H+ gradient − pumped from the matrix into the intermembrane space 3. Oxygen serves as the final electron acceptor in the chain − combine with H+ to form H2O 2.-Chemiosmosis is a movement of Ions across the membrane and down an electrochemical gradient. Oxidative Phosphorylation (per glucose) Input: 6 NADH, 2 FADH2 , O2 , H+ Output: H2O Net Energy Gain: 26-28 ATP “Overview of Metabolism” Objective 6-Metabolism of Lipid and Proteins. Describe starvation Lipid Metabolism = Fat Metabolism Our body uses Fats/Lipids for ATP not so often. Fats store a lot of energy. Triglycerides are 3 fatty acids + 1 Glycerol Lipolysis breaks triglycerides down into glycerol and fatty acid. Glycerol enters Glycolysis. Beta oxidation uses fatty acids to generate Acetyl-Coa (in the mitochondrial Matrix) Acetyl-Coa is used to make fatty acids, cholesterol, ketone bodies. Fatty acids ➔➔Acetyl-Coa➞➞Citric Acid ➞➞Oxidative Phosphorylation ==ATP Protein Metabolism Proteins can also turn into ATP/Energy Protein Removes the Amino Acid group to convert into a Pyruvate Structure of Amino Acid : and Carboxyl Group. Amino group, R Side chain Hydrogen Starvation has 3 faces 1)Carbohydrates (last Min-Hours) 2.)Fat Lipids-Use ketone Bodies (last Days to Weeks) 3.)Proteins (last Weeks to Months) Chapter 5A: Membrane Physiology & “DIFFUSION” Diffusion : Things that are moving across cell membrane from outside to inside Objective 1: DIfferent types of Transport across a plasma membrane Cell Membrane also Known as Plasma membrane found in all cells. Cell Membrane/Plasma membrane separates the interior of the cell (ICF) from the exterior of the cell (ECF). Cell Membrane/ Plasma membrane is made of Phospholipid Bilayer. Phospholipid Bilayer has polar head and nonpolar Tail. How things move across the membrane : Passive transport (Spontaneously) & Active Transport(Not spontaneously). Passive Transport - energy not required “spontaneous” Active transport-Energy required. Protein Mediated : means a membrane protein is needed for stuff to move through it can be active or passive. Protein-Mediated Transport: membrane protein needed for molecules to flow through membrane Objective 2 Diffusion Diffusion is the flow of molecules across a selectively permeable Membrane. What happens if you drop a DYE into a beaker of water. Over time the Dye will be dispersed into the water from High concentration to Low concentration. Diffusion is when it goes from high to low concentration 1.- Once the dye has been dropped in the water a Concentration gradient has been created. 2.- Overtime, the dye molecules will flow from the high concentration area to the low concentration area. 3.- Diffusion will continue to occur until the dye is evenly distributed. When the dye is evenly distributed, there is then no more concentration gradient. Once this occurs,diffusion will STOP. Properties of Diffusion: Property 1: DIffusion is Passive Property 2: In Diffusion , Molecules move from a high concentration to a low concentration. Property 3: Net movement of molecules occurs until the concentrations are equal everywhere. Property 4: Diffusion speed does change if the distance is Short or Long. Property 5 : DIffusion is proportional (directly related) to temperature. Property 6: Diffusion is conversely related to molecular Weight and Size. Property 7: Diffusion will occur, except if there is a barrier that will not allow it to occur. The only energy that occurs in diffusion is the kinetic energy possessed by each molecule Concentration gradient is the difference of the levels of concentration. Diffusion will occur until there is no more concentration gradient. There will be no net movement of molecules when the concentration gradient is gone. Diffusion occurs very fast when there is a short distance between the concentration gradients. However, diffusion occurs slowly if there is a large distance between the concentration gradients. At higher temperatures, molecules move around more rapidly. Because of this, the rate of diffusion increases in increased temperatures. The rate of diffusion increases if the molecular weight is smaller. The plasma membrane only allows certain molecules to diffuse through the plasma membrane. Diffusing through the plasma membrane is when a molecule is moving from the ICF to ECF (or vice versa). The cell membrane is a semi-permeable barrier that separates the ICF and the ECF. Permeable means allowing substances to pass through the cell membrane. Some substances can pass/flow through the membrane easily and may OR may not use a membrane protein to cross the membrane. Examples of these substance will be: Water Small AND uncharged particles (alcohol and steroids) Gas Simple Diffusion is when molecules can flow directly through a cell membrane. Substances that can NOT pass/flow through the membrane easily must us a MEMBRANE PROTEIN to cross the membrane. Examples of substances that will need the help of a Membrane protein Large Molecules (Proteins, amino acids and carbohydrates) Charged Particles (Nucleotides, DNA and RNA) Hydrophilic (Water-loving Molecules) 1) These substances diffuse through the plasma membrane by Facilitated Diffusion. 2) Facilitated diffusion moves solutes across the membrane via transport proteins. 3) Fick's law describes the movement of particles over time. There are a few strategies for maximizing particle movement, such as minimizing the distance the particles have to travel, using smaller molecules, increasing pressure, and increasing surface area. Chapter 5B Osmosis and Tonicity Osmosis is when water moves freely across a membrane. Water will always want to flow from low to high solute concentration. Water mostly diffuses through the membrane through a membrane protein channel called aquaporin. How does osmosis occur? For osmosis to occur: 1)the solute concentration must be different!(it’s a response by water to do something about that difference in concentration). 2.)The net movement of water will eventually stop because there will be equal concentrations of water on both sides (no gradient..... No flow... osmosis stops) 3.)One way we can measure osmosis is osmotic pressure (force to oppose osmosis). The units for osmotic pressure, just as with other pressures in physiology, are atmospheres (atm) or millimeters of mercury (mm Hg). Osmolarity OR Osmolality describes the total amount of solute per volume of fluid (osmol/L OR OsM) How to find the osmolarity of % solutions? Example: What is the osmolarity of a half- normal saline solution (.45%NaCl) 1.) Convert % concentration to g/L.45% to g/L →→→→.45g/100mL multiply each by 10 = 4.5g/1000mL 2.) Turn g/L to mol/L 4.5g/L * 1 mol/58.4g = 0.76 mol/L 3.) Use mol/L to get osmol/L. (osmol/mol will be how many particles your molecule is... for glucose it’s 1 osmol/mole...for NaCl it’s 2 osmol/mo) 0.76mol/L * 2mol/mole =.153 Tonicity (How osmosis affects cell shape- will the cell shrink, burst, or have no change in shape)? Tonicity measures the movement of water into or out of a cell. Hypertonic solution causes a net flow of water out of the cell; cell shrinks Hypotonic solution causes a net flow of water into the cell; the cell swells. Isotonic solution creates no net flow of water into or out of the Cell. Tonicity tells us if a solution will shrink or burst a cell. Hypotonic solution is less concentrated than normal. Hypertonic is more concentrated than normal. Isotonic solution is a normal concentrated solution. Solution A: If the inside of the cell has a higher concentration of solutes than solution A, water will move into the cell and theoretically cause the cell to swell and burst. Solution A is hypotonic. Cells that want fluids should be administered a hypotonic solution. (cells about to shrink). Solution B: If the inside of the cell has a lower concentration of solutes than solution B, water will move out of the cell and theoretically cause the cell to shrink. Solution B is hypertonic. Cells that need to lose fluids should be administered a hypertonic solution (cells about to burst) Solution C: If the inside of the cell has the same concentration of solutes compared to solution C, there will be theoretically no net movement (no more osmosis). Solution C is isotonic. Cells that do not need more/less fluid should be administered isotonic. A Hypotonic B Hypertonic CH.6 Cell Communication Ligand means signal Cells talk to each other to maintain Homeostasis There is 2 types of signaling : 1)Electrical Signaling 2) Chemical SIgnaling Target cells recognize and respond to a specific chemical signal (ligand) ─ must have the correct receptors ─ binding cause conformational change (change in protein receptor shape) ─ cells may have many different receptors. There is 4 examples of local cells signaling/ cell communication in general 1 is Electrical signaling and the other 3 are Chemical Signaling. 1.- Gap Junction (Electrical Signaling) are connections that link the cytoplasm of 2 cells- allowing signals to pass between cells. 2.-Contact‐dependent signals involve interactions between molecules on the surfaces of adjacent cells. 3.- Autocrine signals act on the same cell that secreted them 4. Paracrine signals are secreted by one cell and act on adjacent(next to) cells Long Distance Forms of Cell Communication: This type of cell communication involves one cell communicating with another cell that is far away. Types of long distance forms of cell communication : 1. Endocrine signaling involves releasing chemical signal molecules (called a hormone) into blood. (hormones are molecules secreted by endocrine cells or glands) 2. Neuronal signaling uses both electrical and chemical signals. Neurons are specialized cells that transmit electrical signals Neurotransmitters are secreted by neurons and cross a gap to target. Molecules that are involved in cell Signaling/Communication: *Neurohormones, *Cytokines, *Growth Factors Neurohormones are secreted by neurons into the blood ─ e.g., oxytocin, ADH Cytokines are small cell‐signaling proteins involved in immune response ─ interleukins, chemokines, tumor necrosis factor, interferons. Growth factors are involved with wound repair and cell proliferation ─ includes cytokines and hormones Receptors and Ligands: Specificity and Affinity Receptors receive chemical signals and initiate a cellular response − located on the cell membrane, in the cytosol, or nucleus. Receptors have specificity and may bind one or more different ligands. Receptors can have a different affinity for different ligands − ↑ affinity = more likely to bind − influenced by many factors Receptors and Ligands: Up/Down Regulation & Agonist/Antagonist Response to a ligand can be limited by the number of receptors − down‐regulation decreases the number of functioning receptors − up‐regulation increases the number of functioning receptors. Ligands have different effects when binding to a receptor − agonist ➤ is a ligand that binds to a receptor and triggers a response − antagonist is a ligand that binds to a receptor to block the response ⚫ There are two types of receptors : 1.-Intracellular Receptors 2.-Cell Surface Receptors 1.-Intracellular receptors are found in the cytoplasm or nucleus of a cell. Ligands of intracellular receptors : are small, hydrophobic molecules ─ must cross cell membrane ─ e.g., steroid hormones Hormone‐receptor complex enters nucleus and regulates gene activity ─ binds to DNA molecule ─ alters level of transcription 2.-Cell Surface Receptor :bind to ligands on the outside surface of the cell ─ contain three domains Ligands of Cell Surface receptors : Many different molecules can serve as ligands for cell-surface receptors. ─ no need to cross cell membrane ─ large, hydrophilic molecules ─ e.g., peptide and protein hormones Types of Cell Surface Receptors 1. Ligand‐gated ion channels open or close in response to the binding of a ligand 2. Enzyme‐linked receptors activate intracellular enzymes when ligand binds 3. G protein‐coupled receptors use G proteins to open ion channels in the membrane or alter enzyme activity 4. Integrin receptors alter the cytoskeleton in response to ligand binding Enzyme Linked Receptors Several enzymes are associated with cell surface receptors (if ends with ASE is an enzyme) ─ kinase adds phosphate group ─ phosphatase removes phosphate ─ adenylyl cyclase convert ATP to cAMP ─ phospholipase C converts membrane phospholipids into IP3 and DAG Receptor tyrosine kinases transfers a phosphate group from ATP to tyrosine ─ phosphorylate tyrosine is used to initiate cell response G‐Protein Coupled Receptors (GPCR) G proteins that associate with GPCRs are made up of three subunits ─ alpha (α) binds to GDP and GTP and is involved in cell signaling ─ beta (β) and gamma (γ) regulate alpha and are involved in cell signaling Ligand binding induced conformational change in G protein‐ coupled receptor: 1. Alpha subunit is activated by replacing GDP with GTP 2. Alpha subunit separates from beta and gamma to trigger a response Signal Transduction Signal transduction converts an extracellular signal into a cellular response 1. An extracellular ligand binds to and activates a cell‐surface receptor. 2. Receptor activates enzymes and/or second messengers 3. Enzymes and second messengers may alter ion channels, intracellular Ca2+, or protein activity. 4. Cell responds by altering protein synthesis, metabolism, etc. Signal Cascade and Signal Amplification Signal cascade is a series of reactions that occur in response to a stimulus. One reaction triggers the next. Examples of signal cascade : Intracellular signal pathways Blood clotting Signal amplification turns one signal ligand into many second messengers ─ only need a small amount of ligand ─ each step increases effect size Second Messenger System Second messengers are molecules that pass along a signal initiated at a receptor Ca2+ is used to trigger exocytosis, muscle contraction, enzyme activity, etc. cAMP and cGMP are used to open/close ion channels and activates kinase IP3 is produced from phospholipids and releases Ca2+ into the cytosol DAG is produced from phospholipids and activates protein kinase C Examples of Signal transduction: FIght-or- Flight Fight‐or‐flight response occurs in response to perceived harm or a threat to survival ─ ↑ nutrients and O2 delivery to muscles ─ ↓ blood flow to digestive, urinary, and reproductive systems Fight‐or‐flight response is controlled by the nervous and endocrine systems ─ sympathetic nervous system releases norepinephrine ─ adrenal glands release a hormone called epinephrine