A. Metabolism, Energy, and Life
1. The chemistry of life is organized into metabolic pathways.
•	The totality of an organism’s chemical reactions is called __________.
•	Metabolism is an emergent property of life that arises from interactions between molecules within the orderly environment of the __________.
•	Metabolic __________ begin with a specific molecule, which is then altered in a series of defined steps to form a specific product.
•	A specific __________ catalyzes each step of the pathway.
•	__________ pathways release energy by breaking down complex molecules to simpler compounds.
•	A major pathway of catabolism is __________ __________, in which the sugar glucose is broken down in the presence of oxygen to carbon dioxide and water.
•	__________ pathways consume energy to build complicated molecules from simpler compounds. They are also called __________ pathways.
•	The synthesis of protein from __________ __________ is an example of anabolism.
•	The __________ released by catabolic pathways can be stored and then used to drive anabolic pathways.
•	__________ is fundamental to all metabolic processes, and therefore an understanding of energy is key to understanding how the living cell works.
•	__________ is the study of how organisms manage their energy resources.
2. Organisms transform energy.
•	Energy is the capacity to do __________.
•	Energy exists in various forms, and cells __________ energy from one type into another.
•	__________ energy is the energy associated with the relative motion of objects.
•	Objects in motion can perform work by imparting motion to other matter.
•	Photons of light can be captured and their energy harnessed to power __________ in green plants.
•	__________ energy is kinetic energy associated with the random movement of atoms or molecules.
•	__________ energy is the energy that matter possesses because of its location or structure.
•	__________ energy is a form of potential energy stored in molecules because of the arrangement of their atoms.
•	Energy can be __________ from one form to another.
•	For example, as a boy climbs stairs to a diving platform, he is releasing __________ energy stored in his cells from the food he ate for lunch.
•	The __________ energy of his muscle movement is converted into __________ energy as he climbs higher.
•	As he dives, the __________ energy is converted back to __________ energy.
•	__________ energy is transferred to the water as he enters it.
•	Some energy is converted to __________ due to friction.
3. The energy transformations of life are subject to two laws of__________.
•	Thermodynamics is the study of energy __________.
•	In this field, the term __________ refers to the matter under study and the __________ include everything outside the system.
•	A __________ system, approximated by liquid in a thermos, is isolated from its surroundings.
•	In an __________ system, energy and matter can be transferred between the system and its surroundings.
•	Organisms are __________ systems.
•	They absorb energy—light or chemical energy in the form of organic molecules—and release heat and metabolic waste products such as urea or CO2 to their surroundings.
•	The __________ law of thermodynamics states that energy can be transferred and transformed, but it cannot be created or destroyed.
•	The first law is also known as the principle of__________ of energy.
•	Plants do not produce energy; they transform __________ energy to __________ energy.
•	During every transfer or transformation of energy, some energy is converted to __________, which is the energy associated with the random movement of atoms and molecules.
•	A system can use heat to do work only when there is a temperature difference that results in heat flowing from a warmer location to a cooler one.
•	If temperature is __________, as in a living cell, heat can only be used to warm the organism.
•	Energy transfers and transformations make the universe more __________ due to this loss of usable energy.
•	__________ is a quantity used as a measure of disorder or randomness.
•	The more random a collection of matter, the __________ its entropy.
•	The __________ law of thermodynamics states that every energy transfer or transformation increases the entropy of the universe.
•	While order can __________ locally, there is an unstoppable trend toward __________ of the universe.
•	Much of the increased entropy of the universe takes the form of increasing __________, which is the energy of random molecular motion.
•	In most energy transformations, ordered forms of energy are converted at least partly to __________.
•	Automobiles convert only 25% of the energy in gasoline into __________; the rest is lost as heat.
•	Living cells unavoidably convert organized forms of energy to __________.
•	For a process to occur on its own, without outside help in the form of energy input, it must __________ the entropy of the universe.
•	The word __________ describes a process that can occur without an input of energy.
•	Spontaneous processes need not occur quickly.
•	Some spontaneous processes are instantaneous, such as an __________. Some are very slow, such as the __________ of an old car.
•	Another way to state the second law of thermodynamics is for a process to occur spontaneously, it must increase the __________ of the universe.
•	Living systems create ordered structures from less ordered starting materials.
•	For example, amino acids are ordered into __________ chains.
•	The structure of a multicellular body is __________ and complex.
•	However, an organism also takes in organized forms of matter and energy from its __________ and replaces them with less ordered forms.
•	For example, an animal consumes organic molecules as food and __________ them to low-energy carbon dioxide and water.
•	Over evolutionary time, complex organisms have evolved from __________ ones.
•	This increase in __________ does not violate the second law of thermodynamics.
•	The entropy of a particular system, such as an organism, may decrease as long as the total entropy of the __________—the system plus its surroundings—increases.
•	Organisms are islands of __________ entropy in an increasingly random universe.
•	The evolution of biological order is __________ with the laws of thermodynamics.
4. The free energy change of a reaction tells us whether it is spontaneous.
•	How can we determine which reactions occur spontaneously and which ones require an input of energy?
•	The concept of __________ energy provides a useful function for measuring spontaneity of a system.
•	Free energy is the portion of a system’s energy that is able to perform __________ when temperature and pressure is uniform throughout the system, as in a living cell.
•	The free energy (G) in a system is related to the total __________ (in biological systems, equivalent to energy) (H) and the__________ (S) by this relationship:
•	G = H − TS, where T is __________ in Kelvin units.
•	Increases in temperature amplify the __________ term.
•	Not all the energy in a system is available for work because the entropy component must be __________ from the enthalpy component.
•	What remains is the __________ energy that is available for work.
•	Free energy can be thought of as a measure of the stability of a system.
•	Systems that are__________ in free energy—compressed springs, separated charges, organic polymers—are unstable and tend to move toward a more stable state, one with __________ free energy.
•	Systems that tend to change spontaneously are those that have high __________, low __________, or both.
•	In any spontaneous process, the free energy of a system __________.
•	We can represent this __________ in free energy from the start of a process until its finish by:
•	G = Gfinal state − Gstarting state
•	Or G = H − TS
•	For a process to be __________, the system must either give up __________ (decrease in H), give up __________ (increase in S), or both.
•	G must be __________ for a process to be spontaneous.
•	Every __________ process is characterized by a decrease in the free energy of the system.
•	Processes that have a positive or zero G are never __________.
•	The greater the __________ in free energy, the more __________ a spontaneous process can perform.
•	Nature runs “downhill.”
•	A system at __________ is at maximum stability.
•	In a chemical reaction at equilibrium, the rates of __________ and __________ reactions are equal, and there is no change in the __________ of products or reactants.
•	At equilibrium G = 0, and the system can do no __________.
•	A process is spontaneous and can perform work only when it is moving toward __________.
•	Movements away from equilibrium are nonspontaneous and require the addition of __________ from an outside energy source (the surroundings).
•	Chemical reactions can be classified as either exergonic or endergonic based on free energy.
•	An__________ reaction proceeds with a net release of free energy; G is __________.
•	The magnitude of G for an exergonic reaction is the maximum amount of __________ the reaction can perform.
•	The greater the decrease in free energy, the greater the amount of work that can be done.
•	For the overall reaction of cellular respiration: C6H12O6 + 6O2 -> 6CO2 + 6H2O
•	G = −686 kcal/mol
•	For each mole (180 g) of glucose broken down by respiration, __________ kcal of energy are made available to do work in the cell.
•	The __________ have 686 kcal less free energy than the reactants.
•	An __________ reaction is one that absorbs free energy from its surroundings.
•	Endergonic reactions store energy in molecules; G is __________.
•	Endergonic reactions are __________, and the magnitude of G is the quantity of energy required to __________ the reaction.
•	If cellular respiration releases 686 kcal, then photosynthesis, the reverse reaction, must require an equivalent investment of energy.
•	For the conversion of carbon dioxide and water to sugar, G = __________ kcal/mol.
•	Photosynthesis is strongly __________, powered by the absorption of __________ energy.
•	Reactions in a closed system eventually reach equilibrium and can do no work.
•	A cell that has reached metabolic equilibrium has a G = 0 and is __________!
•	Metabolic __________ is one of the defining features of life.
•	Cells maintain disequilibrium because they are __________ systems. The constant flow of materials into and out of the cell keeps metabolic pathways from ever reaching __________.
•	A cell continues to do __________ throughout its life.
•	A catabolic process in a cell releases __________ energy in a series of reactions, not in a single step.
•	Some reversible reactions of respiration are constantly “pulled” in one direction, as the __________ of one reaction does not accumulate but becomes the __________ in the next step.
•	__________ provides a daily source of free energy for photosynthetic organisms.
•	Nonphotosynthetic organisms depend on a transfer of free energy from photosynthetic organisms in the form of __________ molecules.
5. __________ powers cellular work by coupling exergonic reactions to endergonic reactions.
•	A cell does three main kinds of work:
1.	__________ work, such as the beating of cilia, contraction of muscle cells, and movement of chromosomes during cellular reproduction.
2.	__________ work, the pumping of substances across membranes against the direction of spontaneous movement.
3.	__________ work, driving endergonic reactions such as the synthesis of polymers from monomers.
•	Cells manage their energy resources to do this work by __________ __________, the use of an exergonic process to drive an endergonic one.
•	In most cases, the immediate source of energy to power cellular work is__________.
•	ATP (adenosine triphosphate) is a type of __________ consisting of the nitrogenous base __________, the sugar __________, and a chain of three __________ groups.
•	The bonds between phosphate groups can be broken by __________.
•	Hydrolysis of the end phosphate group forms __________ __________.
•	ATP -> ADP + Pi
•	This reaction releases __________ kcal of energy per mole of ATP under standard conditions (1 M of each reactant and product, 25°C, pH 7).
•	In the cell, G for hydrolysis of ATP is about __________ kcal/mol.
•	While the phosphate bonds of ATP are sometimes referred to as __________ phosphate bonds, these are actually fairly __________ covalent bonds.
•	However, they are unstable, and their hydrolysis yields __________ because the products are more stable.
•	The release of energy during the hydrolysis of ATP comes from the chemical change to a state of __________ free energy, not from the phosphate bonds themselves.
•	Why does the hydrolysis of ATP yield so much energy?
•	Each of the three phosphate groups has a __________ charge.
•	These three like charges are crowded together, and their mutual __________ contributes to the instability of this region of the ATP molecule.
•	Remember two’s company, __________ a crowd!
•	In the cell, the energy from the hydrolysis of ATP is directly coupled to endergonic processes by the transfer of the __________ group to another molecule.
•	This recipient molecule is now __________.
•	This molecule is now more __________ (less stable) than the original unphosphorylated molecules.
•	Mechanical, transport, and chemical work in the cell are nearly always powered by the hydrolysis of __________.
•	In each case, a __________ group is transferred from ATP to another molecule and the phosphorylated molecule undergoes a change that performs __________.
•	ATP is a renewable resource that can be regenerated by the addition of a phosphate group to __________.
•	The energy to phosphorylate ADP comes from __________ reactions in the cell.
•	A working muscle cell recycles its entire pool of ATP once each__________.
•	More than 10 million ATP molecules are consumed and regenerated per __________ per cell.
•	Regeneration of ATP is an __________ process, requiring an investment of energy.
•	G = 7.3 kcal/mol.
•	Catabolic (exergonic) pathways, especially cellular respiration, provide the __________ for the exergonic regeneration of ATP.
•	The chemical __________ energy temporarily stored in __________drives most cellular __________.
B. Enzymes Are Catalytic Proteins
1. Enzymes __________ metabolic reactions by __________ energy barriers.
•	Spontaneous chemical reactions may occur so slowly as to be imperceptible.
•	The hydrolysis of table sugar (sucrose) to glucose and fructose is __________.
•	G = −7 kcal/mol
•	Despite this, your sugar sits in its bowl with no observable hydrolysis.
•	If we add a small amount of the __________ __________ sucrase to a solution of sugar, all the sucrose will be hydrolyzed within seconds.
•	A catalyst is a chemical agent that speeds up the __________ of a reaction without being __________ by the reaction.
•	An enzyme is a __________ protein.
•	Enzymes __________ metabolic pathways.
•	Every chemical reaction involves bond __________ and bond __________.
•	To hydrolyze sucrose, the bond between glucose and fructose must be __________ and new bonds must __________with hydrogen and hydroxyl ions from water.
•	To reach a state where bonds can break and reform, reactant molecules must absorb __________ from their surroundings. When the new bonds of the product molecules form, energy is released as __________ as the molecules assume stable shapes with __________ energy.
•	The initial investment of energy for starting a reaction is the __________energy (EA).
•	Activation energy is the amount of energy necessary to push the reactants over an __________  __________ so that the reaction can proceed.
•	At the summit, the molecules are in an unstable condition, the __________ state.
•	Activation energy may be supplied in the form of __________ that the reactant molecules absorb from the surroundings.
•	The bonds of the reactants break only when the molecules have __________ enough energy to become __________ and, therefore, more reactive.
•	The absorption of thermal energy increases the __________of the reactant molecules, so they collide more often and more forcefully.
•	Thermal agitation of the atoms in the molecules makes __________ more likely to break.
•	As the molecules settle into new, stable bonding arrangements, __________ is released to the surroundings.
•	In __________ reactions, the activation energy is released back to the surroundings, and additional energy is released with the formation of new bonds.
•	For some processes, EA is not high, and the thermal __________ provided by room temperature is sufficient for many reactants to reach the transition state.
•	In many cases, EA is high enough that the transition state is rarely reached and that the reaction hardly proceeds at all. In these cases, the reaction will only occur at a noticeable rate if the reactants are __________.
•	A spark plug provides the __________ to energize a gasoline-oxygen mixture and cause combustion.
•	Without that activation energy, the hydrocarbons of gasoline are too __________ to react with oxygen.
•	Proteins, DNA, and other complex organic molecules are rich in free energy. Their hydrolysis is __________, with the release of large amounts of energy.
•	However, there is not enough __________ at the temperatures typical of the cell for the vast majority of organic molecules to make it over the hump of activation energy.
•	How are the barriers for selected reactions surmounted to allow cells to carry out the processes of life?
•	Heat would speed up reactions, but it would also __________ proteins and __________ cells.
•	Enzymes speed reactions by __________ EA.
•	The __________ state can then be reached even at moderate temperatures.
•	Enzymes do not change __________.
•	They hasten reactions that would occur eventually.
•	Because enzymes are so selective, they determine which chemical processes will occur at any time.
2. Enzymes are substrate specific.
•	The reactant that an enzyme acts on is the __________.
•	The enzyme binds to a substrate, or substrates, forming an enzyme-substrate __________.
•	While the enzyme and substrate are bound, the __________ action of the enzyme converts the substrate to the product or products.
•	The reaction catalyzed by each enzyme is very __________.
•	What accounts for this molecular recognition?
•	The specificity of an enzyme results from its __________-__________ shape.
•	Only a portion of the enzyme binds to the substrate.
•	The __________ __________ of an enzyme is typically a pocket or groove on the surface of the protein into which the substrate fits.
•	The active site is usually formed by only a few __________ __________.
•	The specificity of an enzyme is due to the fit between the __________ __________ and the__________.
•	As the substrate enters the active site, interactions between the substrate and the amino acids of the protein causes the enzyme to change __________ slightly, leading to a tighter __________ __________ that brings chemical groups in position to catalyze the reaction.
3. The active site is an enzyme’s catalytic center.
•	In most cases, substrates are held in the active site by weak interactions, such as __________ bonds and __________ bonds.
•	R groups of a few amino acids on the active site __________ the conversion of substrate to product.
•	The __________ then leaves the active site.
•	A single enzyme molecule can __________ thousands of reactions a second.
•	Enzymes are unaffected by the reaction and are __________.
•	Most metabolic enzymes can catalyze a reaction in both the __________ and __________ directions.
•	The actual direction depends on the relative __________ of products and reactants.
•	Enzymes catalyze reactions in the direction of __________.
•	Enzymes use a variety of mechanisms to lower __________ __________ and __________ up a reaction.
•	In reactions involving more than one reactant, the active site brings substrates together in the correct __________ for the reaction to proceed.
•	As the active site binds the substrate, it may put __________ on bonds that must be broken, making it easier for the reactants to reach the transition state.
•	R groups at the active site may create a microenvironment that is conducive to a specific reaction.
•	An active site may be a pocket of low __________, facilitating H+ transfer to the substrate as a key step in catalyzing the reaction.
•	Enzymes may briefly bind covalently to substrates.
•	Subsequent steps of the reaction restore the R groups within the active site to their original state.
•	The rate that a specific number of enzymes convert substrates to products depends in part on substrate __________.
•	At low substrate concentrations, an increase in substrate concentration speeds __________ to available active sites.
•	However, there is a limit to how fast a reaction can occur.
•	At __________ substrate concentrations, the active sites on all enzymes are engaged.
•	The enzyme is __________.
•	The rate of the reaction is determined by the speed at which the active site can convert __________ to __________.
•	The only way to increase productivity at this point is to add more __________ molecules.
4. A cell’s physical and chemical environment affects enzyme activity.
•	The activity of an enzyme is affected by general environmental conditions, such as __________ and __________.
•	Each enzyme works best at certain __________ conditions, which favor the most active conformation for the enzyme molecule.
•	Temperature has a major impact on reaction rate.
•	As temperature__________, collisions between substrates and active sites occur more frequently as molecules move more rapidly.
•	As temperature increases further, thermal agitation begins to disrupt the weak bonds that stabilize the protein’s active conformation, and the protein __________.
•	Each enzyme has an __________ temperature.
•	Most human enzymes have optimal temperatures of about __________–__________°C.
•	Bacteria that live in hot springs contain enzymes with optimal temperatures of __________°C or above.
•	Each enzyme also has an __________ pH.
•	Maintenance of the active conformation of the enzyme requires a particular pH.
•	This falls between pH __________ and __________ for most enzymes.
•	However, digestive enzymes in the stomach are designed to work best at pH __________, while those in the intestine have an optimum of pH __________.
•	Many enzymes require nonprotein helpers, called __________, for catalytic activity.
•	Cofactors bind permanently or reversibly to the enzyme.
•	Some inorganic cofactors include __________, __________, and __________.
•	Organic cofactors are called __________.
•	Many __________ are coenzymes.
•	Binding by __________ prevents enzymes from catalyzing reactions.
•	If inhibitors attach to the enzyme by covalent bonds, inhibition may be __________.
•	If inhibitors bind by weak bonds, inhibition may be __________.
•	Some reversible inhibitors resemble the substrate and compete for binding to the __________ __________.
•	These molecules are called __________ inhibitors.
•	Competitive inhibition can be overcome by increasing the concentration of the __________.
•	__________ inhibitors impede enzymatic reactions by binding to another part of the molecule.
•	Binding by the inhibitor causes the enzyme to change __________, rendering the __________ __________ less effective at catalyzing the reaction.
•	Toxins and poisons are often __________ enzyme inhibitors.
•	Sarin is the nerve gas that was released by terrorists in the Tokyo subway in 1995.
•	Sarin binds covalently to the R group on the amino acid serine.
•	Serine is found in the active site of acetylcholinesterase, an important nervous system enzyme.
C. The Control of Metabolism
1. Metabolic control often depends on allosteric regulation.
•	In many cases, the molecules that naturally regulate enzyme activity behave like reversible __________ inhibitors.
•	Regulatory molecules often bind weakly to an __________ site, a specific receptor on the enzyme away from the active site.
•	Binding by these molecules can either __________ or __________ enzyme activity.
•	Most allosterically regulated enzymes are constructed of two or more polypeptide chains.
•	Each subunit has its own __________ __________.
•	__________ sites are often located where subunits join.
•	The binding of an __________ stabilizes the conformation that has functional active sites, while the binding of an__________ stabilizes the inactive form of the enzyme.
•	As the chemical conditions in the cell shift, the pattern of allosteric regulation may shift as well.
•	By binding to key __________, reactants and products of ATP hydrolysis may play a major role in balancing the flow of traffic between anabolic and catabolic pathways.
•	For example, ATP binds to several catabolic enzymes allosterically, inhibiting their activity by __________ their affinity for substrate.
•	ADP functions as an __________ of the same enzymes.
•	ATP and ADP also affect key enzymes in anabolic pathways.
•	In this way, allosteric __________ control the rates of key reactions in metabolic pathways.
•	In enzymes with multiple catalytic subunits, binding by a __________ to one active site stabilizes favorable conformational changes at all other subunits, a process called cooperativity.
•	This mechanism amplifies the response of enzymes to substrates, priming the enzyme to accept additional __________.
•	A common method of metabolic control is __________ __________ in which an early step in a metabolic pathway is switched off by the pathway’s final product.
•	The product acts as an inhibitor of an __________ in the pathway.
•	Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed.
2. The localization of enzymes within a cell helps order metabolism.
•	Structures within the cell help bring order to metabolic pathways.
•	A team of enzymes for several steps of a metabolic pathway may be assembled as a __________ complex.
•	The product from the first reaction can then pass quickly to the next__________ until the final product is released.
•	Some enzymes and enzyme complexes have fixed locations within the cells as structural components of particular __________.
•	Others are confined within membrane-enclosed eukaryotic __________.
•	Metabolism, the intersecting set of chemical __________ characteristic of life, is a choreographed interplay of thousands of different kinds of cellular molecules.