Chapter 06 Lecture Outline Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. See separate PowerPoint slides for all figures and tables pre-inserted into PowerPoint without notes.
Chapter 06
Lecture Outline
Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.
See separate PowerPoint slides for all figures and tables pre-inserted into PowerPoint without
notes.
Chapter 6 Energy, Enzymes, and Metabolism
Energy and Chemical Reactions
Enzymes and Ribozymes
Overview of Metabolism
Recycling of Organic Molecules
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Key Concepts:
Energy = ability to promote change or do work
Two forms Kinetic Energy – associated with movement
Potential Energy – due to structure or location
Chemical energy, the energy in molecular bonds, is a form of potential energy
3
Energy and Chemical Reactions
4
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(a) Kinetic energy (b) Potential energy a: © moodboard/Corbis RF; b: © amanaimages/Corbis RF
Laws of Thermodynamics
First Law of Thermodynamics “Law of conservation of energy” Energy cannot be created or destroyed,
but can be transformed from one type to another
Second Law of Thermodynamics Transfer of energy from one form to another
increases the entropy (degree of disorder) of a system
As entropy increases, less energy is available for organisms to use to promote change
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H = G + TS
H = enthalpy or total energy
G = free energy or amount of energy for work
S = entropy or unusable energy
T = absolute temperature in Kelvin (K)
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ΔG = Δ H – T Δ S
Spontaneous reactions
Occur without input of additional energy
Not necessarily fast, can be slow Breakdown of sucrose to CO2 and H2O is
spontaneous, but will take a long time for sugar in a sugar bowl to break down
Key factor is the free energy change – if ΔG is negative, then process is exergonic and spontaneous
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Change in free energy determines direction of chemical reactions
Total energy = Usable energy + Unusable energy
Energy transformations involve an increase in entropy (disorder that cannot be harnessed to do work)
Free energy (G) = amount of energy available to do work Also called Gibbs free energy
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Metabolism: Sum total of all chemical reactions in an organism.
Anabolic reactions: Complex molecules are built from simple molecules; energy input is required.
Catabolic reactions: Complex molecules are broken down to simpler ones and energy is released.
8.1 What Physical Principles Underlie Biological Energy Transformations?
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Increase
More disordered
in entropy
Highly ordered
Figure 8.3 Exergonic Reactions
Exergonic Reactions: Releases free energy, (-ΔG) (spontaneous) Catabolic reactions Order/complexity decreases; Entropy increases +ΔS
Figure 8.3 Endergonic Reactions
Endergonic Reactions Consume free energy (+ΔG) (not spontaneous)
Anabolic reactions
Complexity, order increases -ΔS
• Living systems increase the entropy of the universe
– Use energy to maintain order
– As they increase order, the order in the surroundings decreases
50µm
Detailed anatomy of a root tissue from a buttercup plant.
Biological Order and Disorder
An Analogy for Cellular Respiration
A multistep open hydroelectric system. Cellular respiration is analogous to this system: Glucose is broken down in a series of exergonic reactions that power the work of the cell. The product of each reaction becomes the reactant for the next, so no reaction reaches equilibrium.
∆G < 0
∆G < 0
∆G < 0
Input: Glucose Output: CO2
and ATP
• Living cells do not reach equilibrium
• Catabolic Pathways in a cell releases free energy in a series of reactions not just one
No net change in concentration or chemical activities of products and reactants with time.
At chemical equilibrium, ΔG=0
Rate of the forward and reverse reactions are equal:
The concentrations of A and B determine the direction of the reaction.
Chemical Equilibrium
• A cell that reaches metabolic equilibrium is:
DEAD or ALIVE?
Figure 8.4 Chemical Reactions Run to Equilibrium
A spontaneous reaction is not necessarily a fast reaction
Catalyst – an agent that speeds up the rate of a chemical reaction without being consumed during the reaction
Enzymes – protein catalysts in living cells
Ribozymes – RNA molecules with catalytic properties
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Enzymes and Ribozymes
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Progress of an exergonic reaction
Fre
e en
erg
y (G
)
Transition state
Reactants
Reactant molecules
Enzyme
ATP Glucose
Products
Activation energy (EA) without enzyme
Activation energy (EA) with enzyme
Change in free energy (ΔG)
How enzymes lower activation energy
Straining bonds in reactants to make it easier to achieve transition state
Positioning reactants together to facilitate bonding
Changing local environment Direct participation through very temporary bonding
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Figure 8.9 Enzyme and Substrate
Substrate binding
Enzymes have a high specificity for their substrate
Lock and key metaphor for substrate and enzyme binding – only the right key (substrate) will fit in the lock (enzyme)
Induced fit phenomenon – interaction also involves conformational changes
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Enzyme reactions
Saturation Plateau where nearly all active sites are occupied by
substrate
Vmax = velocity of reaction near maximal rate
Michaelis constant, KM Substrate concentration where velocity is half
maximal value
High KM enzyme needs higher substrate concentration
Inversely related to affinity between enzyme and substrate 22
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Vel
oci
ty
(pro
du
ct/s
eco
nd
)
[Substrate]
A
B Vmax
2
Vmax C
D
A 60 sec Low
B 60 sec Moderate
C 60 sec High
D 60 sec
Reaction velocity in the absence of inhibitors
0
Amount of enzyme
Tube
Incubation time
Substrate concentration
Very high
1 µg 1 µg 1 µg 1 µg
KM
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Enzyme Regulation
Irreversible inhibition: Inhibitor binds to enzyme and has irreversible effects.
Reversible inhibition: Effect of inhibitor is reversible. (This is what cells do)
Competitive inhibition
Noncompetitive inhibition
Figure 8.15 Irreversible Inhibition
DIPF: Diisopropyl Phosphorofluoridate
Inhibition
Competitive inhibition Molecule binds to active site
Inhibits ability of substrate to bind
Apparent KM increases – more substrate needed
Noncompetitive inhibition Lowers Vmax without affecting Km
Inhibitor binds to allosteric site, not active site
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KM with inhibitor [Substrate] Competitive inhibition
Vel
oci
ty
(pro
du
ct/s
eco
nd
) Plus competitive inhibitor
Substrate Inhibitor Enzyme
Vmax
KM [Substrate] Noncompetitive inhibition
Vel
oci
ty
(pro
du
ct/s
eco
nd
)
Substrate Inhibitor
Enzyme Allosteric site
0
0
KM
Vmax
V max with inhibitor
Plus noncompetitive inhibitor
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Competitive inhibition
Vmax
KM [Substrate] Noncompetitive inhibition
Vel
oci
ty
(pro
du
ct/s
eco
nd
)
Substrate Inhibitor
Enzyme Allosteric site
0
V max with inhibitor
Plus noncompetitive inhibitor
KM with inhibitor [Substrate]
Vel
oci
ty
(pro
du
ct/s
eco
nd
)
Plus inhibitor
0 KM
Vmax No inhibitor
Other requirements for enzymes
Prosthetic groups – small molecules permanently attached to the enzyme
Cofactor – usually inorganic ion that temporarily binds to enzyme
Coenzyme – organic molecule that participates in reaction but is left unchanged afterward
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Enzymes are affected by environment
Most enzymes function maximally in a narrow range of temperature and pH
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0 0
10 20
Rat
e o
f a
chem
ical
rea
ctio
n
30 40 50 60
High
Temperature (ºC)
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Chemical reactions occur in metabolic pathways
Redox reactions Substrate level phosphorylation reactions
Each step is coordinated by a specific enzyme
Catabolic pathways Breakdown cellular components Exergonic
Anabolic pathways Synthesis cellular components Endergonic Must be coupled to exergonic reaction
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Overview of Metabolism
Catabolic reactions
Breakdown of reactants
Used for recycling building blocks
Used for energy to drive endergonic reactions Energy stored in intermediates such as ATP, NADH
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Anabolic reactions
Biosynthetic reactions
Make large macromolecules or smaller molecules not available from food
Require energy inputs from intermediates (NADH or ATP) to drive reactions
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Adenine (A)
Ribose
Phosphate groups
Phosphate (Pi) Adenosine diphosphate (ADP)
Adenosine triphosphate (ATP)
+ ~
H H
OH
O
OH
H H
O O O
H2C O–
NH2
N
N H
N
N
P OH O
O–
P O–
O
O–
P HO
~ ~
H H
OH
O
OH
H H
O O O
H2C O–
NH2
N
N H
N
N
P O O
O–
P O
O–
P O–
H2O Hydrolysis of ATP
ΔG = -7.3 kcal/mole
Reaction favors formation of products
The energy liberated is used to drive a variety of cellular processes
Hydrolysis of ATP
Figure 8.7 Coupling of ATP Hydrolysis to an Endergonic Reaction
Redox Reactions
Oxidation-reduction reaction or Redox reaction
Reduction: Gain of one or more electrons (hydrogens)
Oxidation: Loss of one or more electrons (hydrogens)
Both processes occur together
C6H12O6 + 6O2 6CO2 + 6H2O + free energy
Reducing agent becomes oxidized
Oxidizing agent becomes reduced
Reducing Agent
Oxidizing Agent
Redox is also defined as loss/gain of H atoms Loss of H atoms = Oxidation
Gain of H atoms = Reduction
The more reduced a molecule, the more energy is stored in its chemical bonds.
NAD+ acts as an electron carrier
Participates in redox reactions
Highly exergonic ΔG = 50 kcal/mol where as ATP ΔG = 12 kcal/mol
NAD+ + H+ + 2e- NADH
FAD+ is similar carrier
Nicotinamide Adenine Dinucleotide (NAD+)
Figure 9.3 NAD+/NADH is an Electron Carrier in Redox Reactions
NAD+ + H+ + 2e- NADH
Two ways to make ATP
1. Substrate-level phosphorylation Enzyme directly transfers phosphate from one
molecule to another molecule
2. Chemiosmosis Energy stored in an electrochemical gradient is
used to make ATP from ADP and Pi
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Feedback Inhibition of Metabolic Pathways
Committed Step Several Reactions
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Feedback Inhibition
Enzyme 3 Enzyme 1
Initial substrate
Conformational change
Allosteric site
Intermediate 1 Intermediate 2 Final product
Enzyme 2 Active site
Final product
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Feedback Inhibition: If the concentration of the final product becomes high, it will bind to enzyme 1 and cause a conformational change that inhibits the enzyme’s ability to convert the initial substrate into intermediate 1.
Regulation of metabolic pathways
Gene regulation Turn genes on or off
Cellular regulation Cell-signaling pathways like hormones
Biochemical regulation Feedback inhibition – product of pathway inhibits
early steps to prevent over accumulation of product
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Most large molecules exist for a relatively short period of time
Half-life – time it takes for 50% of the molecules to be broken down and recycled
All living organisms must efficiently use and recycle organic molecules
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Recycling of Organic Molecules
Recycling Mechanisms
Exonucleases (Exosome Complex)-mRNA degradation
Proteosome-Protein degradation
Lysosome-Molecule degradation
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