chapter 8 an introduction to metabolism. energy flow energy flow in the life of a cell energy: the...
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Energy Flow in the Life of a Cell
• Energy: • the capacity to
do work
• Two type of Energy• Kinetic: energy of
movement• Potential: stored
energy• Chemical Energy:
PE available to be released in a chemical reaction
Organization of the Chemistry of Life into Metabolic Pathways
• Metabolic Pathway: Begins with a specific molecule, which is then altered in a series of defined steps resulting in a certain product.
Metabolic Pathway
Enzyme 1
A B
Reaction 1
Enzyme 2
C
Reaction 2
Enzyme 3
D
Reaction 3
ProductStarting
molecule
Types of Metabolic pathways
• Catabolic: breakdown pathways (Makes energy available) Downhill– Respiration: Breaks down glucose to produce carbon
dioxide, water and ATP
• Anabolic: Consumes energy and builds molecules (Uphill)– Photosynthesis– Synthesis of a protein
• Bioenergetics: the study of how organisms manage their energy resources.
The Laws of Thermodynamics
• The 1st Law is often called • The Law of conservation
of energy• Assumes that the total
amount of energy is constant.
• 2nd law• As energy is transferred
through the system the amount of useful energy decreases.
• No process is 100% efficient
• Regions of great [energy] are regions of great orderliness.
• Entropy
Living things Use Energy to Organize
• Living things use solar energy to synthesize complex molecules and maintain orderly structures but do this at the expense of enormous loss of usable solar energy.
• Living systers increase the entropy of their surroundings so the entropy of the universe as a whole constantly increases.
• This means that the 2nd law applies.
How Does Energy Flow in Chemical
Reactions?
• Chemical reaction, reactants, products• Exergonic (energy out)• Endergonic (energy in)• Activation energy: the valence ē ‘s of the
reactants must interact and overcome their natural (-) (-) replusion.
Coupled Reactions link Exergonic with Endergonic Reactions
• Endergonic reactions require energy.
• It gets this energy from exergonic reactions.
• Eg. Photosynthesis requires light which comes from the exergonic reaction occurring on the sun.
Concept 8.2: The free-energy changes of a reaction tells us whether the reaction occurs
spontaneously
• 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
Free-Energy Change, G
• 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), and change in entropy (T∆S):
∆G = ∆H - T∆S• Only processes with a negative ∆G are
spontaneous• Spontaneous processes can be harnessed to
perform work
Free Energy, Stability, and Equilibrium
• Free energy 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
• A process is spontaneous and can perform work only when it is moving toward equilibrium
Free Energy and Metabolism
• The concept of free energy can be applied to the chemistry of life’s processes
Exergonic and Endergonic Reactions in Metabolism
• 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
LE 8-6a
Reactants
EnergyProducts
Progress of the reaction
Amount ofenergy
released(G < 0)
Fre
e en
erg
y
Exergonic reaction: energy released
LE 8-6b
ReactantsEnergy
Products
Progress of the reaction
Amount ofenergy
required(G > 0)
Fre
e en
erg
y
Endergonic reaction: energy required
Equilibrium and Metabolism• Reactions in a closed system eventually reach
equilibrium and then do no work
• Cells are not in equilibrium; they are open systems experiencing a constant flow of materials
• A catabolic pathway in a cell releases free energy in a series of reactions
• Closed and open hydroelectric systems can serve as analogies
Concept 8.3: ATP powers cellular work by coupling exergonic
reactions to endergonic reactions
• A cell does three main kinds of work:– Mechanical– Transport– Chemical
• To do work, cells manage energy resources by energy coupling, the use of an exergonic process to drive an endergonic one
The Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate) is the cell’s energy shuttle
• ATP provides energy for cellular functions
LE 8-9
Adenosine triphosphate (ATP)
Energy
P P P
PPP i
Adenosine diphosphate (ADP)Inorganic phosphate
H2O
+ +
• The bonds between the phosphate groups of ATP’s tail can be broken by hydrolysis
• Energy is released from ATP when the terminal phosphate bond is broken
• This release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves
• 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
The Regeneration of ATP• ATP is a renewable resource that is
regenerated by addition of a phosphate group to ADP
• The energy to phosphorylate ADP comes from catabolic reactions in the cell
• The chemical potential energy temporarily stored in ATP drives most cellular work
LE 8-10
Endergonic reaction: G is positive, reactionis not spontaneous
Exergonic reaction: G is negative, reactionis spontaneous
G = +3.4 kcal/mol
G = –7.3 kcal/mol
G = –3.9 kcal/mol
NH2
NH3Glu Glu
Glutamicacid
Coupled reactions: Overall G is negative;together, reactions are spontaneous
Ammonia Glutamine
ATP H2O ADP P i
+
+ +
LE 8-11
NH2
Glu
P i
P i
P i
P i
Glu NH3
P
P
P
ATPADP
Motor protein
Mechanical work: ATP phosphorylates motor proteins
Protein moved
Membraneprotein
Solute
Transport work: ATP phosphorylates transport proteins
Solute transported
Chemical work: ATP phosphorylates key reactants
Reactants: Glutamic acidand ammonia
Product (glutamine)made
+ +
+
Electron Carriers also Transport Energy
• Excited ē’s are created during photosynthesis and cellular respiration.
• These energized ē’s are captured by electron carriers and then donated to other molecules.
• Examples: NADP+, NAD+, FAD
How Do Cells Control Their Metabolic Reactions?
1. Cells regulate chemical reations through the use of enzymes.
2. Cells couple reactions.
3. Cells synthesize energy-carrier moleucles that capture energy from exergonic reaction and transport it to endergonic reactions.
Concept 8.4: Enzymes speed up metabolic reactions by lowering
energy barriers
• A catalyst is a chemical agent that speeds up a reaction without being consumed by the reaction
• An enzyme is a catalytic protein
• Hydrolysis of sucrose by the enzyme sucrase is an example of an enzyme-catalyzed reaction
At Body Temperature, Spontaneous Reactions Proceed Too Slowly to Sustain Life
• Enzymes lower the activation energy but are not used up or permanently altered.
3 Important Principles about Catalysts
• Catalysts speed up reaction
• Catalysts can speed up only those reactions that would occur spontaneously anyway, but at a much slower rate
• Catalysts are not consumed in the reactions they promote.
The Activation Energy Barrier• 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 (EA)
• Activation energy is often supplied in the form of heat from the surroundings
LE 8-14
Transition state
C D
A B
EA
Products
C D
A B
G < O
Progress of the reaction
Reactants
C D
A B
Fre
e en
erg
y
How Enzymes Lower the EA Barrier
• Enzymes catalyze reactions by lowering the EA barrier
• Enzymes do not affect the change in free-energy (∆G); instead, they hasten reactions that would occur eventually
Animation: How Enzymes Work
LE 8-15
Course ofreactionwithoutenzyme
EA
without enzyme
G is unaffectedby enzyme
Progress of the reaction
Fre
e en
erg
y
EA withenzymeis lower
Course ofreactionwith enzyme
Reactants
Products
Substrate Specificity of Enzymes
• 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
Catalysis in the Enzyme’s Active Site
• In an enzymatic reaction, the substrate binds to the active site
• The active site can lower an EA barrier by
– Orienting substrates correctly– Straining substrate bonds– Providing a favorable microenvironment– Covalently bonding to the substrate
LE 8-17
Enzyme-substratecomplex
Substrates
Enzyme
Products
Substrates enter active site; enzymechanges shape so its active siteembraces the substrates (induced fit).
Substrates held inactive site by weakinteractions, such ashydrogen bonds andionic bonds.
Active site (and R groups ofits 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.
Substrates areconverted intoproducts.
Products arereleased.
Activesite is
availablefor two new
substratemolecules.
Effects of Local Conditions on Enzyme Activity
• An enzyme’s activity can be affected by:– General environmental factors, such as
temperature and pH– Chemicals that specifically influence the
enzyme
Effects of Temperature and pH
• Each enzyme has an optimal temperature in which it can function
• Each enzyme has an optimal pH in which it can function
LE 8-18
Optimal temperature fortypical human enzyme
Optimal temperature forenzyme of thermophilic (heat-tolerant bacteria)
Temperature (°C)
Optimal temperature for two enzymes
0 20 40 60 80 100
Ra
te o
f re
ac
tio
n
Optimal pH for pepsin(stomach enzyme)
Optimal pHfor trypsin(intestinalenzyme)
pH
Optimal pH for two enzymes
0
Ra
te o
f re
ac
tio
n
1 2 3 4 5 6 7 8 9 10
Enzyme Inhibitors• 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
LE 8-19Substrate
Active site
Enzyme
Competitiveinhibitor
Normal binding
Competitive inhibition
Noncompetitive inhibitor
Noncompetitive inhibition
A substrate canbind normally to the
active site of anenzyme.
A competitiveinhibitor mimics the
substrate, competingfor the active site.
A noncompetitiveinhibitor binds to the
enzyme away from theactive site, altering the
conformation of theenzyme so that its
active site no longerfunctions.
Concept 8.5: Regulation of enzyme activity helps control
metabolism
• Chemical chaos would result if a cell’s metabolic pathways were not tightly regulated
• To regulate metabolic pathways, the cell switches on or off the genes that encode specific enzymes
Allosteric Regulation of Enzymes
• Allosteric regulation is the term used to describe cases where a protein’s function at one site is affected by binding of a regulatory molecule at another site
• Allosteric regulation may either inhibit or stimulate an enzyme’s activity
Allosteric Activation and Inhibition
• Most allosterically regulated enzymes are made from polypeptide subunits
• Each enzyme has active and inactive forms• The binding of an activator stabilizes the active
form of the enzyme• The binding of an inhibitor stabilizes the
inactive form of the enzyme
LE 8-20a
Allosteric enzymewith four subunits
Regulatorysite (oneof four) Active form
Activator
Stabilized active form
Active site(one of four)
Allosteric activatorstabilizes active form.
Non-functionalactive site
Inactive formInhibitor
Stabilized inactive form
Allosteric inhibitorstabilizes inactive form.
Oscillation
Allosteric activators and inhibitors
• Cooperativity is a 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
LE 8-20b
Substrate
Binding of one substrate molecule toactive site of one subunit locks allsubunits in active conformation.
Cooperativity another type of allosteric activation
Stabilized active formInactive form
Feedback Inhibition
• In feedback inhibition, the end product of a metabolic pathway shuts down the pathway
• Feedback inhibition prevents a cell from wasting chemical resources by synthesizing more product than is needed
LE 8-21
Active siteavailable
Initial substrate(threonine)
Threoninein active site
Enzyme 1(threoninedeaminase)
Enzyme 2
Intermediate A
Isoleucineused up bycell
Feedbackinhibition Active site of
enzyme 1 can’tbindtheoninepathway off
Isoleucinebinds toallostericsite
Enzyme 3
Intermediate B
Enzyme 4
Intermediate C
Enzyme 5
Intermediate D
End product(isoleucine)
Specific Localization of Enzymes Within the Cell
• Structures within the cell help bring order to metabolic pathways
• Some enzymes act as structural components of membranes
• Some enzymes reside in specific organelles, such as enzymes for cellular respiration being located in mitochondria