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Slide 1
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
PowerPoint® Lecture Presentations for
BiologyEighth Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero, updated by Erin Barley with contributions from Joan Sharp
Chapter 8
An Introduction to Metabolism
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Slide 2
• Metabolism in an organism is about energy and enzymes.
• It is the sum of all of the chemical reactions performed by the cells of the organism.
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Slide 3
1. Free Energy
2. Kinetic energy
3. Heat (thermal energy)
4. Potential energy
5. Chemical energy
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Energy cannot be converted from one form to another.
True or False?
a) E that matter possesses because of its location or structure
b) Kinetic E associated with random movement of atoms or molecules
c) Potential E available for release in a chemical reaction
d) E associated with motion
e) The capacity to cause change (can be used to do work)
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Slide 4 Metabolism
• Thermodynamics says that the flow of chemical energy into an organism is equal to the energy used as work, the energy lost as heat and the chemical potential energy stored by the organism.
– true for organisms
– true for the tissues in an organism
– true for the individual cells in a tissue
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Slide 5 Fig. 8-UN1
Enzyme 1 Enzyme 2 Enzyme 3DCBA
Reaction 1 Reaction 3Reaction 2
Starting moleculesproteins
carbohydrateslipids
polymers v. monomers
Productswork energyheat energy
chemical energy
storage = potential
Enzymes make it ALL happen!
Metabolic Pathway
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Slide 6 Fig. 8-6
Reactants
Energy
Free
ene
rgy
Products
Amount ofenergy
released(∆G < 0)
Progress of the reaction
Products
ReactantsEnergy
Free
ene
rgy
Amount ofenergy
required(∆G > 0)
Progress of the reaction
• An exergonicreaction proceeds with a net releaseof energy
• An endergonicreaction absorbsenergy from its surroundings
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Slide 7 Metabolic pathways
• Catabolic pathways release energy (exergonic) by breaking down complex molecules into simpler compounds
– Examples?
• Anabolic pathways consume energy (endergonic) to build complex molecules from simpler ones
– Examples?
• Work pathways couple the energy derived from exergonic reactions to perform an endergonic activity – together the whole is always exergonic
– Do we harness all of the exergonic energy?
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Slide 8 Fill in the Chart
Reaction 1:ATP + H2O ADP + Pi
Reaction 2:6CO2 + 6H2O C6H12O6 + 6O2
Exergonic/Endergonic
Anabolic/Catabolic
Energy Requirements
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Slide 9 Fill in the Chart
Reaction 1:ATP + H2O ADP + Pi
Reaction 2:6CO2 + 6H2O C6H12O6 + 6O2
Exergonic/Endergonic Exergonic Endergonic
Anabolic/Catabolic Catabolic – break down Anabolic – synthesis reaction
Energy Requirements E is released requires the input of E
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Slide 10 ATP powers cellular work
• 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 11 Fig. 8-8
Phosphate groupsRibose
Adenine
ATP is composed of ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups
What are the two cellular roles of ATP?
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Slide 12 Fig. 8-9
Inorganic phosphate
Energy
Adenosine triphosphate (ATP)
Adenosine diphosphate (ADP)
P P
P P P
P ++
H2O
i
What is the name of this
reaction?
Is this an exergonic or endogonic reaction?
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Slide 13 Fig. 8-11
(b) Mechanical work: ATP binds noncovalentlyto motor proteins, then is hydrolyzed
Membrane protein
P i
ADP+
P
Solute Solute transported
P i
Vesicle Cytoskeletal track
Motor protein Protein moved
(a) Transport work: ATP phosphorylatestransport proteins
ATP
ATP
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Slide 14 Fig. 8-12
Energy for cellularwork (endergonic,energy-consumingprocesses)
P iADP +
Energy fromcatabolism (exergonic,energy-releasingprocesses)
ATP + H2O
ATP is a renewable resource that is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)
The energy to phosphorylate ADP comes from catabolic reactions in the cell
Where in the cell does this occur?
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Slide 15 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 16 Fig. 8-13
Sucrose (C12H22O11)
Glucose (C6H12O6) Fructose (C6H12O6)
Sucrase
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Slide 17 Fig. 8-15
Progress of the reaction
Glucoseandfructose
sucroseand H2O
Course ofreactionwithoutenzyme
EAwithoutenzyme EA with
enzymeis lower
Course ofreactionwith enzyme
Enzymes catalyze reactions by lowering the EA barrier
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Slide 18 Substrate Specificity of Enzymes
• The reactant that an enzyme acts on is called the enzyme’s ___________.
• The ________is the region on the enzyme where it binds
• This binding is extremely specific (sucrase –recognizes sucrose, not maltose). Why?
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 19 Fig. 8-16
Substrate
Active site
Enzyme Enzyme-substratecomplex
(b)(a)
Hexokinase - first enzyme in the breakdown of glucose (glycolysis)
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Slide 20 Catalysis in the Enzyme’s Active Site
• In an enzymatic reaction, the substrate binds to the active site of the enzyme
• The active site can lower an EA barrier by:– Orienting substrates correctly
– Straining substrate bonds– Providing a favorable microenvironment
– Covalently bonding to the substrate
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 21 Fig. 8-17
Substrates
Enzyme
Products arereleased.
Products
Substrates areconverted toproducts.
Active site can lower EAand speed up a reaction.
Substrates held in active site by weakinteractions, such as hydrogen bonds andionic bonds.
Substrates enter active site; enzyme changes shape such that its active siteenfolds the substrates (induced fit).
Activesite is
availablefor two new
substratemolecules.
Enzyme-substratecomplex
5
3
21
6
4
Induced fit of a substrate brings
chemical groups of the active site into
positions that enhance their
ability to catalyze the reaction
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Slide 22 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 23 Fig. 8-18
Rat
e of
rea
ctio
n
Optimal temperature forenzyme of thermophilic
(heat-tolerant) bacteria
Optimal temperature fortypical human enzyme
(a) Optimal temperature for two enzymes
(b) Optimal pH for two enzymes
Rat
e of
rea
ctio
n
Optimal pH for pepsin(stomach enzyme)
Optimal pHfor trypsin(intestinalenzyme)
Temperature (ºC)
pH543210 6 7 8 9 10
0 20 40 80 60 100
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Slide 24 Cofactors
• Cofactors are nonprotein enzyme helpers
• Cofactors may be inorganic (such as a metal in ionic form) or organic
• An organic cofactor is called a coenzyme
• Coenzymes include vitamins
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 25 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
• Examples of inhibitors include toxins, poisons, pesticides, and antibiotics
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 26 Fig. 8-19
(a) Normal binding (c) ___________ inhibition(b) ___________ inhibition
inhibitor
Active siteinhibitor
Substrate
Enzyme
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Slide 27 CONNECTION
• Many poisons, pesticides, and drugs are enzyme inhibitors
Cyanide - binds competitively and irreversibly to cytochrome oxidase, an enzyme involved in ATP production during cellular respiration
Penicillin - binds competitively and irreversibly to transpeptidase, an enzymeneeded for the growth of bacterial cell walls - humans lack this enzyme
Ibuprofen and aspirin - bind competitively to cyclooxygenases, the enzymes thatmake prostaglandins, chemicals that promote inflammation (and can lead to pain and fever)
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Slide 28 Concept 8.5: Regulation of enzyme activity helps control metabolism
• Metabolic pathways must be tightly regulated
• A cell does this by switching on or off the genes that encode specific enzymes or by regulating the activity of enzymes (once they are made)
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 29 Allosteric Regulation of Enzymes
• Allosteric regulation occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site
• Allosteric regulation may either inhibit or stimulate an enzyme’s activity
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 30 Fig. 8-20a
(a) Allosteric activators and inhibitors
InhibitorNon-functionalactivesite
Stabilized inactiveform
Inactive form
Oscillation
ActivatorActive form Stabilized active form
Regulatorysite (oneof four)
Allosteric enzymewith four subunits
Active site(one of four)
Allosterically regulated enzymes:
• Usually polypeptidesubunits
• have active and inactiveforms
• binding of eitheractivators or inhibitors stabilize the enzyme
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Slide 31 Fig. 8-20b
(b) Cooperativity: another type of allosteric activation
Stabilized activeform
Substrate
Inactive form
• 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
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Slide 32 Cooperativity and Hemoglobin
http://en.wikibooks.org/wiki/Structural_Biochemistry/Protein_function/Heme_group/Hemoglobin
When one oxygen binds a heme, the rest bind more easily. When the first oxygen is released, it stimulates the release of the others. This is due to conformational changes in the hemoglobin subunits.
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Slide 33 Identification of Allosteric Regulators
• Allosteric regulators are attractive drug candidates for enzyme regulation
• Inhibition of proteolytic enzymes called caspases may help management of inappropriate inflammatory responses
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
Animation: http://bcs.whfreeman.com/thelifewire/content/chp06/0602002.html
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Slide 34 Fig. 8-21a
SH
Substrate
Hypothesis: allostericinhibitor locks enzymein inactive form
Active form canbind substrate
S–SSH
SH
Activesite
Caspase 1
Known active form
Known inactive form
Allostericbinding site
Allostericinhibitor
EXPERIMENT
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Slide 35 Fig. 8-21b
Caspase 1
RESULTS
Active formInhibitor
Allostericallyinhibited form
Inactive form
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Slide 36 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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Slide 37 Fig. 8-22
Intermediate C
Feedbackinhibition
Isoleucineused up bycell
Enzyme 1(threoninedeaminase)
End product(isoleucine)
Enzyme 5
Intermediate D
Intermediate B
Intermediate A
Enzyme 4
Enzyme 2
Enzyme 3
Initial substrate(threonine)
Threoninein active site
Active siteavailable
Active site ofenzyme 1 nolonger bindsthreonine;pathway isswitched off.
Isoleucinebinds toallostericsite
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Slide 38 Specific Localization of Enzymes Within the Cell
• Cellular structures help bring order to metabolic pathways
• Some enzymes act as structural components of membranes
• In eukaryotic cells, some enzymes reside in specific organelles; for example, enzymes for cellular respiration are located in mitochondria
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings
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