chapter 8 an introduction to metabolism. fig. 8-1
TRANSCRIPT
Chapter 8Chapter 8
An Introduction to Metabolism
Fig. 8-1
I. Metabolism
• The totality of an organism’s chemical reactions
II. Metabolic Pathways
• Begins with a specific molecule and ends with a product
• Each step is catalyzed by a specific enzyme
Enzyme 1 Enzyme 2 Enzyme 3
DCBA
• Catabolic pathways: release energy, break down molecules
• Ex. Cellular respiration - breakdown of glucose with oxygen
• Anabolic pathways: consume energy, build complex molecules
• Ex. Synthesis of protein from amino acids
III. Forms of Energy (E)
• Energy = capacity to cause change
• Kinetic E = E from motion
• Heat (thermal E) = KE from random movement of atoms or molecules
• Potential E = E because of location or structure
• Chemical E = PE available for release in a reaction
• Energy can be converted from one form to another
Fig. 8-2
Climbing up converts the kineticenergy of muscle movementto potential energy.
A diver has less potentialenergy in the waterthan on the platform.
Diving convertspotential energy tokinetic energy.
A diver has more potentialenergy on the platformthan in the water.
IV. The Laws of Energy Transformation
• Thermodynamics = the study of energy transformations
• Closed system = isolated from surroundings
• Open system = energy and matter can be transferred between system and surroundings
• Organisms = open systems
A. The First Law of Thermodynamics
• Energy of the universe is constant:
– Energy can be transferred and transformed, but it cannot be created or destroyed
• Principle of conservation of energy
B. The Second Law of Thermodynamics
• During every energy transfer or transformation, some energy is unusable, and is lost as heat
– Every energy transfer or transformation increases the entropy (disorder) of the universe
Chemicalenergy
Heat CO2
H2O
V. Free-Energy Change, G
• Free energy = available energy to do work when temp and pressure are uniform
• Change in free energy (∆G) during a process is related to the change in enthalpy (change in total energy (∆H)), change in entropy (disorder (∆S)), and temp in Kelvin (T):
∆G = ∆H – T∆S
• Only processes with a negative ∆G are spontaneous and can be harnessed to do work
• Free Energy Bozeman
VI. Free Energy and Metabolism
• Exergonic reaction proceeds with a net release of free energy (ΔG < 0) and is spontaneous
• Endergonic reaction absorbs free energy from its surroundings (ΔG > 0) and is nonspontaneous
Fig. 8-6
Reactants
Energy
Fre
e e
ne
rgy
Products
Amount ofenergy
released(∆G < 0)
Progress of the reaction
(a) Exergonic reaction: energy released
Products
ReactantsEnergy
Fre
e e
ne
rgy
Amount ofenergy
required(∆G > 0)
(b) Endergonic reaction: energy required
Progress of the reaction
A. 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
Fig. 8-7a
(a) An isolated hydroelectric system
∆G < 0 ∆G = 0
Fig. 8-7b
(b) An open hydroelectric system
∆G < 0
Fig. 8-7c
(c) A multistep open hydroelectric system
∆G < 0
∆G < 0
∆G < 0
VIII. Structure and Hydrolysis of ATP
• ATP (adenosine triphosphate) is the cell’s energy shuttle
• ATP = ribose (a sugar), adenine (a nitrogenous base), and three phosphate groups
• ATP Overview - Bozeman
• Bonds between the phosphate groups can be broken by hydrolysis (releasing energy)
• This release of energy comes from the chemical change to a state of lower free energy, not from the phosphate bonds themselves
Fig. 8-9
Inorganic phosphate
Energy
Adenosine triphosphate (ATP)
Adenosine diphosphate (ADP)
P P
P P P
P ++
H2O
i
X. How ATP Performs Work
• ATP powers 3 types of cellular work (mechanical, transport, and chemical)
• Energy from the exergonic reaction of ATP hydrolysis can be used to drive an endergonic reaction (energy coupling)
• Overall, coupled reactions are exergonic
• ATP drives endergonic reactions by transferring a phosphate group to some other molecule (phosphorylation)
Fig. 8-10
(b) Coupled with ATP hydrolysis, an exergonic reaction
Ammonia displacesthe phosphate group,forming glutamine.
(a) Endergonic reaction
(c) Overall free-energy change
PP
GluNH3
NH2
Glu i
GluADP+
PATP+
+
Glu
ATP phosphorylatesglutamic acid,making the aminoacid less stable.
GluNH3
NH2
Glu+
Glutamicacid
GlutamineAmmonia
∆G = +3.4 kcal/mol
+2
1
Fig. 8-11
(b) Mechanical work: ATP binds noncovalently to motor proteins, then is hydrolyzed
Membrane protein
P i
ADP+
P
Solute Solute transported
Pi
Vesicle Cytoskeletal track
Motor protein Protein moved
(a) Transport work: ATP phosphorylates transport proteins
ATP
ATP
XI. The Regeneration of ATP
• ATP is regenerated by addition of a phosphate group to adenosine diphosphate (ADP)
• The energy comes from catabolic reactions in the cell
• The chemical PE temporarily stored in ATP drives most cellular work
Fig. 8-12
P iADP +
Energy fromcatabolism (exergonic,energy-releasingprocesses)
Energy for cellularwork (endergonic,energy-consumingprocesses)
ATP + H2O
XII. Activation Energy
• Initial E needed to start a chemical reaction is the free energy of activation, or activation energy (EA)
• Activation energy is often supplied from heat
Fig. 8-14
Progress of the reaction
Products
Reactants
∆G < O
Transition state
Fre
e en
erg
y EA
DC
BA
D
D
C
C
B
B
A
A
XIII. Enzymes Lower the EA
• Enzymes catalyze reactions by lowering the EA
• Enzymes do not affect the change in free energy (∆G); they hasten reactions that would occur eventually
Fig. 8-15
Progress of the reaction
Products
Reactants
∆G is unaffectedby enzyme
Course ofreactionwithoutenzyme
Fre
e en
erg
y
EA
withoutenzyme EA with
enzymeis lower
Course ofreactionwith enzyme
XIV. Substrate Specificity of Enzymes
• substrate = reactant that an enzyme acts on
• enzyme-substrate complex = enzyme binding to its substrate
• Active site = region on enzyme where the substrate binds
• Induced fit = brings chemical groups of active site into positions that enhance their ability to catalyze the reaction
• Enzyme Overview - Bozeman
Fig. 8-16
Substrate
Active site
Enzyme Enzyme-substratecomplex
(b)(a)
XV. Enzyme’s 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
Fig. 8-17
Substrates
Enzyme
Products arereleased.
Products
Substrates areconverted toproducts.
Active site can lower EA
and 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
XVI. Effects on Enzyme Activity
• An enzyme’s activity can be affected by
– Each enzyme has optimum Temp and pH
– Chemicals that influence the enzyme (cofactors and inhibitors)
Fig. 8-18
Ra
te o
f re
ac
tio
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
Ra
te o
f re
ac
tio
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
A. Cofactors
• Nonprotein enzyme helpers
• May be inorganic (such as a metal in ionic form) or organic
• Coenzyme = organic cofactor (vitamins)
B. Enzyme Inhibitors
• Competitive inhibitors bind to active site of enzyme, competing w/ substrate
• Noncompetitive inhibitors bind to another part of enzyme, causing enzyme to change shape and making active site less effective
• Ex. toxins, poisons, pesticides, and antibiotics
Fig. 8-19
(a) Normal binding (c) Noncompetitive inhibition(b) Competitive inhibition
Noncompetitive inhibitor
Active siteCompetitive inhibitor
Substrate
Enzyme
XVII. Allosteric Regulation of Enzymes
• Allosteric regulation = inhibit or stimulate an enzyme’s activity
• Occurs when a regulatory molecule binds to a protein at one site and affects the protein’s function at another site
A Allosteric Activation and Inhibition
• Most allosterically regulated enzymes are made from polypeptide subunits
• Each enzyme has active (activator stabilizes) and inactive (inhibitor stabilizes) forms
Fig. 8-20a
(a) Allosteric activators and inhibitors
InhibitorNon-functionalactivesite
Stabilized inactiveform
Inactive form
Oscillation
Activator
Active form Stabilized active form
Regulatorysite (oneof four)
Allosteric enzymewith four subunits
Active site(one of four)
• Cooperativity = form of allosteric regulation that can amplify enzyme activity
• Binding by a substrate to one active site stabilizes favorable conformational changes at all other subunits
Fig. 8-20b
(b) Cooperativity: another type of allosteric activation
Stabilized activeform
Substrate
Inactive form
B. Feedback Inhibition
• End product of a metabolic pathway shuts down the pathway
• Prevents cell from wasting chemical resources by making more product than needed
• Biochemical Pathway (no inhibition)
• Feedback Inhibition of Biochemical Pathways
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