Overview: The Energy of Life The living cell is a miniature chemical factory where thousands of chemical reactions occur The cell moves energy around and changes its form as it applies energy to perform work: energy transduction. Examples: Some organisms light energy to chemical energy, as in photosynthesis. Others convert chemical energy to light, as in bioluminescence

Concept 8.1: An organism’s metabolism transforms matter and energy, subject to the laws of thermodynamics One way to look at metabolism is to examine the chemical reactions that occur. Reactions are organized in a series called a metabolic pathway. A metabolic pathway begins with a specific molecule and ends with a product The reactions need a catalyst to speed them up Each reaction is catalyzed by a specific enzyme

Diagram of a simple metabolic pathway Enzyme 1Enzyme 2Enzyme 3 D CB A Reaction 1Reaction 3Reaction 2 Starting molecule Product

Catabolic pathways release energy by breaking down complex molecules into simpler compounds (catabolism) Cellular respiration, the breakdown of glucose in the presence of oxygen, is an example of a pathway of catabolism Anabolic pathways consume energy to build complex molecules from simpler ones (anabolism) The synthesis of protein from amino acids is an example of anabolism

Energy flow and transfer in metabolism Another way to look at metabolism is to follow energy flow (bioenergetics) Energy is defined as the capacity to cause change Energy exists in various forms, some of which can perform work

Main Types of Energy in Biological Systems Kinetic energy is energy associated with motion Heat (thermal energy) is kinetic energy associated with random movement of atoms or molecules Potential energy is energy that matter possesses because of its location or structure Chemical energy is potential energy available for release in a chemical reaction Energy can be converted from one form to another- this is called energy transduction

Two Key Laws of Energy Transduction Thermodynamics is the study of energy transformations According to the first law of thermodynamics, the energy of the universe is constant: – Energy can be transferred and transformed, but it cannot be created or destroyed The first law is also called the principle of conservation of energy

During every energy transfer or transformation, some energy is unusable (often lost as waste heat) TANSTAAFL According to the second law of thermodynamics : – Every energy transfer or transformation increases the entropy (disorder) of the universe

Living systems have to obey these two laws. They survive because they are open systems. A closed system is isolated from its surroundings But in an open system, energy and matter can be transferred between the system and its surroundings Organisms import and export energy (including entropy) and matter.

The functioning of individual cells does not violate the second law. The evolution of more complex organisms does not violate the second law of thermodynamics Entropy (disorder) may decrease within the boundaries of a cell or an organism or a species as long as the universe’s total entropy increases

Concept 8.2: The free-energy change of a reaction tells us whether or not the reaction occurs spontaneously To understand how living systems operate, biologists want to know which reactions occur spontaneously and which require input of energy To do so, they need to determine energy changes that occur in chemical reactions A living system’s free energy is energy that can do work when temperature and pressure are uniform, as in a living cell

The change in free energy (∆G) during a process is related to the change in enthalpy, or change in total energy (∆H) after the entropy change (∆S) has been subtracted: ∆G = ∆H – T∆S Only processes with a negative ∆G are spontaneous Spontaneous negative ∆G processes can be harnessed to perform work

Overall free energy content(G not ∆G) is a measure of a system’s instability, its tendency to change to a more stable state During a spontaneous change, free energy decreases and the stability of a system increases Equilibrium is a state of maximum stability so a process always has a -∆G as it moves toward equilibrium A process is spontaneous and can perform work only when it is moving toward equilibrium

Examples Spontaneous change Spontaneous change Spontaneous change (b) Diffusion(c) Chemical reaction(a) Gravitational motion

The concept of free energy can be applied to the chemistry of life’s processes-allows definition of 2 types of reactions An exergonic reaction proceeds with a net release of free energy and is spontaneous An endergonic reaction absorbs free energy from its surroundings and is nonspontaneous

Graphic Explanation Reactants Energy Free energy Products Amount of energy released (∆G < 0) Progress of the reaction (a) Exergonic reaction: energy released Products Reactants Energy Free energy Amount of energy required (∆G > 0) (b) Endergonic reaction: energy required Progress of the reaction

(a) An isolated hydroelectric system ∆G < 0∆G = 0

(b) An open hydroelectric system ∆G < 0

(c) A multistep open hydroelectric system: cells and organisms have a series of molecular machines to capture some of the energy released ∆G < 0

Reactions in a closed system eventually reach equilibrium and then do no work But cells and organisms are not in equilibrium; they are open systems experiencing a constant flow of materials and energy Something that is alive is never at equilibrium

Concept 8.3: ATP powers cellular work by coupling exergonic reactions to endergonic reactions A cell does three main kinds of work: – Chemical – Transport – Mechanical To do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one Most energy coupling in cells is mediated by ATP- because ATP hydrolysis is highly exergonic

The Structure and Hydrolysis of ATP ATP (adenosine triphosphate) is the cell’s energy shuttle ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups

Structure of ATP Adenine (a base) + ribose (a sugar) = adenosine +3 phosphates = triphosphate Phosphate groups Ribose Adenine

The bonds between the phosphate groups of ATP’s tail (“phosphate bonds”) can be broken by hydrolysis Energy is released from ATP when the terminal phosphate bond is broken (rarely the other bonds) The difference between products and reactants under cellular conditions is the key

Hydrolysis of ATP to ADP and P i Inorganic phosphate Energy Adenosine triphosphate (ATP) Adenosine diphosphate (ADP) P P P PP P + + H2OH2O i Delta G varies with conditions

Cellular work is powered primarily by the hydrolysis of ATP In the cell, the energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction Overall, the coupled reactions are exergonic One of the ways that ATP shuttles energy is by transfer of the terminal phosphate group (phosphorylation reaction)

Example of endergonic and exergonic reactions coupled by ATP (b) Coupled with ATP hydrolysis, an exergonic reaction Ammonia displaces the phosphate group, forming glutamine. (a) Endergonic reaction (c) Overall free-energy change P P Glu NH 3 NH 2 Glu i ADP + P ATP + + Glu ATP phosphorylates glutamic acid, making the amino acid less stable. Glu NH 3 NH 2 Glu + Glutamic acid Glutamine Ammonia ∆G = +3.4 kcal/mol + 2 1

ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP) P i ADP + Energy from catabolism (exergonic, energy-releasing processes) Energy for cellular work (endergonic, energy-consuming processes) ATP + H2OH2O Endergonic and exergonic reactions are linked or “coupled” through ATP

NOTE CARD MARCH 4 Review: Explain the difference between free energy and entropy.

Concept 8.4: Enzymes speed up metabolic reactions by lowering energy barriers Even spontaneous reactions do not automatically happen quickly A catalyst is a chemical agent that speeds up a reaction but is not consumed by the reaction An enzyme is a catalytic protein Enzymes increase the rate of metabolic reactions. Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction

Sucrose (C 12 H 22 O 11 ) Glucose (C 6 H 12 O 6 ) Fructose (C 6 H 12 O 6 ) Sucrase

Every chemical reaction between molecules involves bond breaking and bond forming The initial energy needed to start a chemical reaction is called the free energy of activation, or activation energy (E A ) Enzymes speed up reactions by lowering the energy of activation

Progress of the reaction Products Reactants ∆G is unaffected by enzyme Course of reaction without enzyme Free energy E A without enzyme E A with enzyme is lower Course of reaction with enzyme

Enzymes catalyze reactions by lowering the E A barrier Enzymes do not affect the change in free energy (∆G); instead, they hasten reactions that would occur eventually Enzymes change reaction rate-not reaction energy

The reactant that an enzyme acts on is called the enzyme’s substrate The enzyme binds to its substrate, forming an enzyme-substrate complex The active site is the region on the enzyme where the substrate binds Induced fit of a substrate brings chemical groups of the active site into positions that enhance their ability to catalyze the reaction Induced fit helps the reactants move into the transition state

Substrates Enzyme Products are released. Substrates are converted to products. Active site can lower E A and speed up a reaction. Substrates held in active site by weak interactions, such as hydrogen bonds and ionic bonds. Substrates enter active site; enzyme changes shape such that its active site enfolds the substrates (induced fit). Active site is available for two new substrate molecules. Enzyme-substrate complex

An enzyme’s activity can be affected by general environmental factors – temperature or pH – Chemicals that specifically influence the enzyme – Availability of substrate

Each enzyme has a temperature at which it functions best This is called the temperature optimum for the enzyme Each enzyme has an optimal pH at which it functions best This is called the pH optimum for the enzyme Temperature and pH affect an enzyme by altering its shape or configuration

Some chemicals can specifically influence enzymes by aiding the reaction Cofactors are nonprotein enzyme helpers The provide additional chemical flexibility and they take part in the enzyme’s reaction Cofactors may be inorganic (such as a metal in ionic form) or organic An organic cofactor is called a coenzyme Frequently, coenzymes are produced from vitamins in the diet

Some chemicals can specifically influence enzymes without participating in the reaction Competitive inhibitors bind to the active site of an enzyme, competing with the substrate Noncompetitive inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective Examples of inhibitors include toxins, poisons, pesticides, and antibiotics- alpha amanitin from the death cap mushroom is a specific example

Competitive and Noncompetitive inhibition Competitive-blocks the active site “If the substrate won’t fit-then the enzyme must quit” Noncompetitive-works by changing the conformation of the enzyme Some inhibitors are permanent and some are reversible (a) Normal binding (c) Noncompetitive inhibition (b) Competitive inhibition Noncompetitive inhibitor Active site Competitive inhibitor Substrate Enzyme

Concept 8.5: Regulation of enzyme activity helps control metabolism Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated Metabolic reactions and pathways are conrolled by enzymes Therefore living systems can regulate their metabolism by regulating their enzymes

A fundamental way to turn off an enzyme reaction is by not having the enzyme around. Turning off enzyme synthesis = enzyme repression; turning it on = enzyme induction (both are slow) Another fundamental way to regulate is to control the amount of substrate No substrate = no reaction; increasing substrate = increasing reaction-but only up to a point where the enzyme is working as fast as it can: saturation.

1. Induction/repression = slow 2. Substrate concentration = limited 3. pH and temperature = not always practical or possible 4. Inhibitors = hard to control and may not be reversible Better method needed for quick and flexible control of enzyme reactions Allosteric regulation: control of enzyme reaction by reversible shape change

Allosteric regulation may either inhibit or stimulate an enzyme’s activity (positive/negative allosteric regulation) Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site

(b) Cooperativity: another type of allosteric activation Stabilized active form Substrate Inactive form Cooperativity is one important form of allosteric regulation that can amplify enzyme activity In cooperativity, binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits

Feedback inhibition, is a metabolic control strategy that usually involves allosteric regulation In feedback inhibition, the end product of a metabolic pathway shuts down the pathway Feedback inhibition prevents a cell from synthesizing more product than the cell need- this avoids wasting of chemical resources

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

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