An Introduction to Metabolism

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Chapter 8

• An Introduction to Metabolism

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• Concept 8.1 An organisms metabolism transforms
  matter and energy, subject to the laws of
  thermodynamics

• Metabolism
• Is the totality of an organisms chemical
  reactions
• manages the material and energy resources of the
  cell.

• A metabolic pathway has many steps
• begin with a specific molecule and end with a
  product
• are each catalyzed by a specific enzyme

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• Catabolic pathways (breakdown pathways)
• Break down complex molecules into simpler
  compounds
• Release energy

• ex. cellular respiration,
• (the sugar glucose and other organic fuels
  are broken down
• in the presence of oxygen to carbon
  dioxide and water)

• Anabolic pathways (biosynthetic pathways)
• Build complicated molecules from simpler ones
• Consume energy

• ex. synthesis of a protein from amino acids.

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Forms of Energy

• Energy
• Is the capacity to cause change.
• Exists in various forms, of which some can
  perform work.

The work of life depends on the ability of cells
to transform energy from one type into another.
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• Kinetic energy
• Is the energy associated with motion
• heat, or thermal energy, is kinetic energy
  associated with the random movement of atoms or
  molecules
• Potential energy
• Is stored in the location or structure of matter
• Includes chemical energy stored in molecular
  structure.

is a term used by biologists to refer to the
potential energy available for release in a
chemical reaction
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• Energy can be converted from one form to another
• --- organisms are energy transformers.

On the platform, a diver has more potential
energy.
Diving converts potential energy to kinetic
energy.
Figure 8.2
Climbing up converts kinetic energy of muscle
movement to potential energy.
In the water, a diver has less potential energy.
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The Laws of Energy Transformation

• Thermodynamics
• Is the study of energy transformations.
• Two laws of thermodynamics govern energy
  transformations in organisms and all other
  collections of matter.

The First Law of Thermodynamics

• According to the first law of thermodynamics
• The energy of universe is constant.
• (Energy can be transferred and transformed
• , but it cannot be created or destroyed)
• The principle of conservation of energy.

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• An example of energy conversion

Chemical energy
(a)
First law of thermodynamics Energy can be
transferred or transformed but Neither created
nor destroyed. For example, the chemical
(potential) energy in food will be converted to
the kinetic energy of the cheetahs movement in
(b).
Figure 8.3 
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The Second Law of Thermodynamics
During every energy transfer or transformation,
some energy becomes unusable energy, unavailable
to do work.
(the energy associated with the random motion
of atoms or molecules)
Heat
entropy as a measure of disorder, or
randomness.
?
Heat
co2

H2O
(b)
Second law of thermodynamics Every energy
transfer or transformation increases the disorder
(entropy) of the universe. For example, disorder
is added to the cheetahs surroundings in the
form of heat and the small molecules that are the
by-products of metabolism.
Figure 8.3 
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Second law of thermodynamics Every energy
transfer or transformation increases the
disorder (entropy) of the universe.
A process to occur on its own, without outside
help (an input of energy), it must increase
the entropy of the universe. ? Spontaneous
? Nonspontaneous
Another way to state the second law is For a
process to occur spontaneously, it must increase
the entropy of the universe.
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Free-Energy Change, ?G

• Concept 8.2 The free-energy change of a reaction
  tells us whether the reaction occurs spontaneously

• A living systems free energy
• Is energy that can do work under cellular
  conditions

• The change in free energy, ?G, during a
  biological process
• is related directly to the enthalpy change (?H)
  and the change in entropy

?
?G ?H T?S ?G G final state G initial
state
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Free Energy, Stability, and Equilibrium

• Organisms live at the expense of free energy
• During a spontaneous change
• Free energy decreases and the stability of a
  system increases

Only processes with a negative ?G are
spontaneous which means that every
spontaneous process decreases the
systems free energy.

• At maximum stability
• The system is at equilibrium

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• A process is spontaneous and can perform work
  only when it is moving toward equilibrium.

• More free energy (higher G)
• Less stable
• Greater work capacity

• In a spontaneously change
• The free energy of the system decreases
  (?Glt0)
• The system becomes more stable
• The released free energy can
• be harnessed to do work

• Less free energy (lower G)
• More stable
• Less work capacity

(a)
(b)
(c)
Chemical reaction. In a cell, a sugar molecule is
broken down into simpler molecules.
Diffusion. Molecules in a drop of dye diffuse
until they are randomly dispersed.
Gravitational motion. Objects move spontaneously
from a higher altitude to a lower one.
Figure 8.5 
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Free Energy and Metabolism
Exergonic and Endergonic Reactions in Metabolism

• An exergonic reaction (??)
• Proceeds with a net release of free energy and is
  spontaneous

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• An endergonic reaction (??)
• Is one that absorbs free energy from its
  surroundings and is nonspontaneous

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Equilibrium and Metabolism

• Reactions in a closed system
• Eventually reach equilibrium

?G lt 0
?G 0
(a) A closed hydroelectric system. Water flowing
downhill turns a turbine that drives a generator
providing electricity to a light bulb, but only
until the system reaches equilibrium.
Figure 8.7 A
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• Cells in our body
• Experience a constant flow of materials in and
  out, preventing metabolic pathways from reaching
  equilibrium

(b) An open hydroelectric system. Flowing
water keeps driving the generator because
intake and outflow of water keep the system
from reaching equlibrium.
?G lt 0
Figure 8.7
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• An analogy for cellular respiration

?G lt 0
?G lt 0
?G lt 0
Figure 8.7
(c) A multistep open hydroelectric system.
Cellular respiration is analogous to this
system Glucoce is brocken 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.
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• 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

• A key feature in the way cells manage their
  energy resources to do this work
• ? Energy coupling (the use of an exergonic
  process to drive an endergonic one require ATP)

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The Structure and Hydrolysis of ATP

• ATP (adenosine triphosphate)
• Is the cells energy shuttle
• Provides energy for cellular functions

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• Energy is released from ATP
• When the terminal phosphate bond is broken

P
P
P
exergonic
Adenosine triphosphate (ATP)
H2O
Figure 8.9
Energy

P
P
P i
Inorganic phosphate
Adenosine diphosphate (ADP)
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• ATP hydrolysis
• Can be coupled to other reactions

Endergonic reaction ?G is positive, reaction is
not spontaneous
NH2
NH3
Glu
Glu
?G 3.4 kcal/mol

Glutamic acid
Ammonia
Glutamine
Exergonic reaction ? G is negative, reaction is
spontaneous
?G - 7.3 kcal/mol
ADP

P
ATP
H2O

Coupled reactions Overall ?G is negative
together, reactions are spontaneous
?G 3.9 kcal/mol
Figure 8.10
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How ATP Performs Work ?

• ATP drives endergonic reactions
• By phosphorylation, transferring a phosphate to
  other molecules

• The three types of cellular work
• Are powered by the hydrolysis of ATP

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The Regeneration of ATP
ATP is a renewable resource that can be
regenerated by the addition of phosphate to
ADP ATP cycle
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The Activation Energy Barrier

• 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

• The initial investment of energy for starting a
  reaction the energy required to contort the
  reactant molecules so the bonds can change.

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• The hydrolysis of sucrose
• Is an example of a chemical reaction

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• The activation energy, EA
• Is the initial amount of energy needed to start a
  chemical reaction
• Is often supplied in the form of heat from the
  surroundings in a system

• The energy profile for an exergonic reaction

EA
Free energy
?G lt O
Progress of the reaction
Figure 8.14
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How Enzymes Lower the EA Barrier

• An enzyme catalyzes reactions
• By lowering the EA barrier

• The effect of enzymes on reaction rate

Course of reaction without enzyme
EA
without enzyme
EA with enzyme is lower
Reactants
Free energy
?G is unaffected by enzyme
Course of reaction with enzyme
Products
Progress of the reaction
Figure 8.15
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Substrate Specificity of Enzymes

• The substrate
• Is the reactant an enzyme acts on
• The enzyme
• Binds to its substrate, forming an
  enzyme-substrate complex

Catalysis in the Enzymes Active Site

• In an enzymatic reaction
• The substrate binds to the active site

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• 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 chemical reaction

Enzyme- substrate complex
(b)
Figure 8.16
Figure 8.16
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• The catalytic cycle of an enzyme

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• The active site can lower an EA barrier by
• Orienting substrates correctly
• Straining substrate bonds
• Providing a favorable microenvironment
• Covalently bonding to the substrate

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Effects of Local Conditions on Enzyme Activity

• The activity of an enzyme
• Is affected by general environmental factors

Effects of Temperature and pH

• Each enzyme
• Has an optimal temperature in which it can
  function

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• Has an optimal pH in which it can function

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Cofactors

• Cofactors
• Are nonprotein enzyme helpers
• Bind tightly to the enzyme as permanent
  residents, or they may bind loosely and
  reversibly along with the substrate.
• Ex. inorganic metal atoms.
• Coenzymes
• Are organic cofactors ex. vitamins

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Enzyme Inhibitors
Reversible inhibition --- inhibitor binds to
the enzyme by weak bond. 1. competitive
inhibitor (inhibitors resemble the normal
substrate molecule and compete for
binding to active site) 2. non competitive
inhibitor (do not directly compete with the
substrate to bind to the enzyme at the
active site) ? change the shape of active site
Irreversible inhibition --- inhibitor attaches
to the enzyme by covalent bonds.
Ex. Toxins and poisons. (the small molecule from
a nerve gas, sarin, binds covalently to the R
group on the amino acid serine which is found in
the active site of acetylcholinesterase, and
enzyme important in the nervous system)
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Enzyme Inhibitors

• Competitive inhibitors
• Bind to the active site of an enzyme, competing
  with the substrate

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• Noncompetitive inhibitors
• Bind to another part of an enzyme, changing the
  function

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• Concept 8.5 Regulation of enzyme activity helps
  control metabolism

• A cells metabolic pathways
• --- Must be tightly regulated
• --- by controlling when and where its
  various
• enzymes are active.
• The molecular that naturally regulate enzyme
  activity in a cell behave like reversible
  noncompetitive inhibitors.
• Allosteric regulation
• --- Is the term used to describe any case in
  which a proteins function at one site is
  affected by binding of a regulatory molecule at
  another site.

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Allosteric Activation and Inhibition

• Many enzymes are allosterically regulated

Constructed from two or more polypeptide
chains, or subunits. The entire complex
oscillate between catalytically active and
inactive state. A single activator or
inhibitor molecule that binds to one regulatory
site will affect the active sites of all subunits.
allosteric site
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• Cooperativity
• Is a form of allosteric regulation that can
  amplify enzyme activity

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Feedback Inhibition

• In feedback inhibition
• The end product of a metabolic pathway shuts down
  the pathway

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Specific Localization of Enzymes Within the Cell

• Within the cell, enzymes may be
• Grouped into complexes
• Incorporated into membranes

• Contained inside organelles