Aim: Why is energy a vital aspect of all life Aim: Why is energy a vital aspect of all life? Do Now: Look at slide 3 in your notes. Describe what you see in as much detail as possible. Homework: Read chapter 6 and complete… Sect. 6.1 q. 1 and 2 pg. 119 Sect. 6.2 q. 1 and 2 pg. 122 Sect. 6.3 q. 1, 2 and 3 pg. 124 Sect. 6.4 q.1 and 2 pg. 130 Sect. 6.5 q. 1 pg. 132

An Introduction to Metabolism Chapter 6 An Introduction to Metabolism

The Energy of Life In this chapter: Every form of life requires energy to perform its daily functions. Some uses of energy include: Cellular Respiration: extracting and breaking down sugars stored in food and converting them to a usable form. Bioluminescence: organisms convert stored energy found in organic molecules into light. In this chapter: You will understand how matter and energy flow during life’s processed and how that flow is regulated.

Two Metabolic Pathways: Catabolic Pathways: a pathway that releases energy by breaking down complex molecules into simpler ones. Anabolic Pathways: pathways that consume energy in order to build complicated molecules from simpler ones.

Energy and its Different Forms Energy: the capacity to do work. Kinetic Energy: energy of movement Thermal Energy (heat): is the kinetic energy associated with the random movement of atoms or molecules Potential Energy: energy of position or location Chemical Energy: the potential energy available in a chemical reaction Ex: Glucose is said to have a high chemical energy

Laws of Thermodynamics Thermodynamics: study of energy transformations that occur in a collection of matter Entropy: a measure of disorder and randomness The First Law of Thermodynamics: Energy can be transferred and transformed, but it cannot be created or destroyed. The Second Law of Thermodynamics: Every energy transfer or transform increases the entropy of the universe.

*The free-energy change of reaction tells us whether or not the reaction occurs spontaneously* Gibbs Free Energy (G): Is the portion of a system’s energy that can perform work when temperature and pressure are uniform throughout the system, as in a living cell. Important because ΔG is used to predict if a particular process is energetically favorable. If ΔG is negative, the reaction can occur with no input of energy. Therefore the ΔG of reaction tells us if the reaction is spontaneous or not.

Chemical Equilibrium: is when the forward and reverse reactions occur at the same rate, there is no net change in the concentration of reactants and products. A process is spontaneous and can perform work only when it is moving towards equilibrium.

Exergonic and Endergonic Reactions Exergonic Reaction: “Energy outward” proceeds with the net release of energy. Since energy is lost, the ΔG value decreases. Therefore exergonic reactions have negative ΔG values. The reaction is spontaneous.

Endergonic Reaction: “Energy inward” is one the absorbs free energy from its surroundings. This kind of reaction stores free energy in molecules therefore ΔG increases. A positive ΔG means that the reaction is not spontaneous.

IMPORTANT NOTES ABOUT METABOLISM Because systems at equilibrium are at a minimum G and can do no work, a cell that has reached metabolic equilibrium is dead! Metabolism as a whole is never at equilibrium A living cell (like most systems) is not in equilibrium because there is a constant flow of materials in and out of the cell. This keeps the metabolic pathways from ever reaching equilibrium. The cell continues to do work throughout its life.

*ATP powers cellular work by coupling exergonic reactions to endergonic reactions* A cell does three main kinds of work: Mechanical: For example the beating of cilia, the contraction of muscle cells, and the movement of chromosomes during cellular reproduction. Transport: The pumping of substances across membranes against the direction of spontaneous movement. Chemical: The pushing of endergonic reactions that will not occur spontaneously, such as the synthesis of polymers from monomers.

The three types of cellular work Are powered by the hydrolysis of ATP (c) Chemical work: ATP phosphorylates key reactants P Membrane protein Motor protein P i Protein moved (a) Mechanical work: ATP phosphorylates motor proteins ATP (b) Transport work: ATP phosphorylates transport proteins Solute transported Glu NH3 NH2 + Reactants: Glutamic acid and ammonia Product (glutamine) made ADP Figure 8.11

Energy coupling: Is a key feature in the way cells manage their energy resources to do this work. Is the use of an exergonic process to drive an endergonic one. ATP is responsible for mediating most energy coupling in cells, and in most cases it acts as the immediate source of energy that powers cellular work.

The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) Is the cell’s energy shuttle. Provides usable energy for cellular functions. Figure 8.8 O CH2 H OH N C HC NH2 Adenine Ribose Phosphate groups - CH

This bond can be broken via hydrolysis (the addition of water). Energy is released from ATP when the terminal phosphate bond is broken. At that point ATP becomes ADP. This bond can be broken via hydrolysis (the addition of water). Figure 8.9 P Adenosine triphosphate (ATP) H2O + Energy Inorganic phosphate Adenosine diphosphate (ADP) P i

How ATP Hydrolysis Performs Work With the help of specific enzymes the cell uses energy released by ATP hydrolysis to drive reactions that alone are endergonic. ATP drives endergonic reactions by phosphorylation, which involves the transferring of a phosphate to an other molecule. If the ΔG of an endergonic reaction is less than the amount of energy released by ATP hydrolysis the two reactions couple so that the overall coupled reactions are exergonic. -

∆G = –3.9 kcal/mol - - ∆G = +3.4 kcal/mol Glu ∆G = + 7.3 kcal/mol ATP Endergonic reaction: ∆G is positive, reaction is not spontaneous ∆G = +3.4 kcal/mol Glu ∆G = + 7.3 kcal/mol ATP H2O + NH3 ADP NH2 Glutamic acid Ammonia Glutamine Exergonic reaction: ∆ G is negative, reaction is spontaneous P Coupled reactions: Overall ∆G is negative; together, reactions are spontaneous ∆G = –3.9 kcal/mol Figure 8.10 - -

The Regeneration of ATP Catabolic pathways drive the regeneration of ATP from ADP and phosphate ATP synthesis from ADP + P i requires energy ATP ADP + P i Energy for cellular work (endergonic, energy- consuming processes) Energy from catabolism (exergonic, energy yielding processes) ATP hydrolysis to ADP + P i yields energy Figure 8.12

Aim: Why is energy a vital aspect of all life Aim: Why is energy a vital aspect of all life? Do Now: Give an example of and describe an endergonic reaction. Homework: -Work on Monday nights HW which is due on Wednesday -Study for exam on chapters 2A/B, 3 and 6

*Enzymes speed up metabolic reactions by lowering energy barriers (Activation energy). Catalyst: is a chemical agent that speeds up a reaction without being consumed by the reaction. Enzyme: is a catalytic protein.

The activation energy, EA : Is the initial amount of energy needed to start a chemical reaction. Is often supplied in the form of heat from the surroundings in a system.

Progress of the reaction The energy profile for an exergonic reaction Free energy Progress of the reaction ∆G < O EA Figure 8.14 A B C D Reactants Transition state Products

Progress of the reaction The effect of enzymes on reaction rate Progress of the reaction Products Course of reaction without enzyme Reactants with enzyme EA EA with is lower ∆G is unaffected by enzyme Free energy Figure 8.15

Substrate Specificity of Enzymes Substrate: is the reactant an enzyme acts on. Enzyme: binds to its substrate, forming an enzyme-substrate complex.

Active site: is the region on the enzyme where the substrate binds. Figure 8.16 Substate Active site Enzyme (a)

Induced Fit Model: Induced fit brings chemical groups of the active site into positions that enhance their ability to catalyze a chemical reaction. In an enzyme reaction the substrate binds. Figure 8.16 (b) Enzyme- substrate complex

The catalytic cycle of an enzyme Substrates Products Enzyme Enzyme-substrate complex 1 Substrates enter active site; enzyme changes shape so its active site embraces the substrates (induced fit). 2 Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. 3 Active site (and R groups of its amino acids) can lower EA and speed up a reaction by • acting as a template for substrate orientation, • stressing the substrates and stabilizing the transition state, • providing a favorable microenvironment, • participating directly in the catalytic reaction. 4 Substrates are Converted into Products. 5 Products are Released. 6 Active site Is available for two new substrate Mole. Figure 8.17

The active site can lower an EA barrier by Orienting substrates correctly Straining substrate bonds Providing a favorable microenvironment Covalently bonding to the substrate

Effects of Local Conditions on Enzyme Activity The activity of an enzyme is affected by general environmental factors

Effects of Temperature and pH Each enzyme has an optimal temperature in which it can function Figure 8.18 Optimal temperature for enzyme of thermophilic Rate of reaction 20 40 80 100 Temperature (Cº) (a) Optimal temperature for two enzymes typical human enzyme (heat-tolerant) bacteria

(b) Optimal pH for two enzymes Has an optimal pH in which it can function Figure 8.18 Rate of reaction (b) Optimal pH for two enzymes Optimal pH for pepsin (stomach enzyme) Optimal pH for trypsin (intestinal enzyme) 1 2 3 4 5 6 7 8 9

Cofactors: Are non-protein helpers that assist with catalytic activities Are bound tightly to the enzyme as permanent residents, or may bind loosely and reversibly with the substrate Some cofactors are inorganic (zinc, iron, copper) , while some are organic Coenzymes: Are organic cofactors Many vitamins are important in nutrition because they act as coenzymes or raw materials from which coenzymes are made

(b) Competitive inhibition Enzyme Inhibitors Competitive inhibitors: bind to the active site of an enzyme, competing with the substrate Figure 8.19 (b) Competitive inhibition A competitive inhibitor mimics the substrate, competing for the active site. Competitive inhibitor A substrate can bind normally to the active site of an enzyme. Substrate Active site Enzyme (a) Normal binding

(c) Noncompetitive inhibition Noncompetitive inhibitors: bind to another part of an enzyme, changing the function Figure 8.19 A noncompetitive inhibitor binds to the enzyme away from the active site, altering the conformation of the enzyme so that its active site no longer functions. Noncompetitive inhibitor (c) Noncompetitive inhibition

Regulation of enzyme activity helps control metabolism Allosteric regulation Is the term used to describe any case in which a protein’s function at one site is affected by binding of a regulatory molecule at another site. Many enzymes are allosterically regulated.

Stabilized active form They change shape when regulatory molecules bind to specific sites, affecting function Stabilized inactive form Allosteric activater stabilizes active from Allosteric enyzme with four subunits Active site (one of four) Regulatory site (one of four) Active form Activator Stabilized active form Allosteric activater stabilizes active form Inhibitor Inactive form Non- functional active site (a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again. Oscillation Figure 8.20

Stabilized active form Cooperativity Is a form of allosteric regulation that can amplify enzyme activity Figure 8.20 Binding of one substrate molecule to active site of one subunit locks all subunits in active conformation. Substrate Inactive form Stabilized active form (b) Cooperativity: another type of allosteric activation. Note that the inactive form shown on the left oscillates back and forth with the active form when the active form is not stabilized by substrate.

In feedback inhibition The end product of a metabolic pathway shuts down the pathway

Figure 8.21 Initial substrate (threonine) Active site available Isoleucine used up by cell Feedback inhibition Isoleucine binds to allosteric site Active site of enzyme 1 no longer binds threonine; pathway is switched off Initial substrate (threonine) Threonine in active site Enzyme 1 (threonine deaminase) Intermediate A Intermediate B Intermediate C Intermediate D Enzyme 2 Enzyme 3 Enzyme 4 Enzyme 5 End product (isoleucine) Figure 8.21

Specific Localization of Enzymes Within the Cell Within the cell, enzymes may be: Grouped into complexes Incorporated into membranes Contained inside organelles 1 µm Mitochondria, sites of cellular respiraion Figure 8.22