An Introduction to Metabolism

1
Chapter 8

• An Introduction to Metabolism

2
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

3
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.

4
Metabolic Pathway
Enzyme 1
Enzyme 2
Enzyme 3
A
B
C
D
Reaction 1
Reaction 2
Reaction 3
Starting molecule
Product
5
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.

6
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

7
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.

8
How Does Energy Flow in Chemical Reactions?

• Chemical reaction, reactants, products
• Exergonic (energy out)
• Endergonic (energy in)
• Activation energy the valence e s of the
  reactants must interact and overcome their
  natural (-) (-) replusion.

9
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.

10
Examples of other coupled reactions
ATP
ADP
P

ATP
Unflexed arm
ADP
P



11
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

12
Free-Energy Change, ?G

• A living systems free energy is energy that can
  do work when temperature and pressure are
  uniform, as in a living cell.

13

• 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

14
Free Energy, Stability, and Equilibrium

• Free energy is a measure of a systems
  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

15
LE 8-5
Gravitational motion
Diffusion
Chemical reaction
16
Free Energy and Metabolism

• The concept of free energy can be applied to the
  chemistry of lifes processes

17
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

18
LE 8-6a
Reactants
Amount of energy released (?G lt 0)
Energy
Free energy
Products
Progress of the reaction
Exergonic reaction energy released
19
LE 8-6b
Products
Amount of energy required (?G gt 0)
Free energy
Energy
Reactants
Progress of the reaction
Endergonic reaction energy required
20
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

21
LE 8-7a
?G lt 0
?G 0
A closed hydroelectric system
22
LE 8-7b
?G lt 0
An open hydroelectric system
23
LE 8-7c
?G lt 0
?G lt 0
?G lt 0
A multistep open hydroelectric system
24
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

25
The Structure and Hydrolysis of ATP

• ATP (adenosine triphosphate) is the cells energy
  shuttle
• ATP provides energy for cellular functions

26
LE 8-8
Adenine
Phosphate groups
Ribose
27
LE 8-9
P
P
P
Adenosine triphosphate (ATP)
H2O

P
P
P
Energy

i
Adenosine diphosphate (ADP)
Inorganic phosphate
28

• The bonds between the phosphate groups of ATPs
  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

29

• 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

30
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

31
LE 8-10
Endergonic reaction DG is positive, reaction is
not spontaneous
NH2
NH3
DG 3.4 kcal/mol

Glu
Glu
Ammonia
Glutamine
Glutamic acid
Exergonic reaction DG is negative, reaction is
spontaneous
P
DG 7.3 kcal/mol
ATP
ADP
H2O


i
Coupled reactions Overall DG is
negative together, reactions are spontaneous
DG 3.9 kcal/mol
32
LE 8-11
P
i
P
Motor protein
Protein moved
Mechanical work ATP phosphorylates motor proteins
Membrane protein
ADP
ATP

P
i
P
P
i
Solute transported
Solute
Transport work ATP phosphorylates transport
proteins
P
NH2
NH3
P


Glu
i
Glu
Reactants Glutamic acid and ammonia
Product (glutamine) made
Chemical work ATP phosphorylates key reactants
33
Electron Carriers also Transport Energy

• Excited es are created during photosynthesis and
  cellular respiration.
• These energized es are captured by electron
  carriers and then donated to other molecules.
• Examples NADP, NAD, FAD

34
How Do Cells Control Their Metabolic Reactions?

• Cells regulate chemical reations through the use
  of enzymes.
• Cells couple reactions.
• Cells synthesize energy-carrier moleucles that
  capture energy from exergonic reaction and
  transport it to endergonic reactions.

35
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

36
At Body Temperature, Spontaneous Reactions
Proceed Too Slowly to Sustain Life

• Enzymes lower the activation energy but are not
  used up or permanently altered.

37
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.

38
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

39
LE 8-14
A
B
C
D
Transition state
EA
A
B
Free energy
C
D
Reactants
A
B
DG lt O
C
D
Products
Progress of the reaction
40
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
41
LE 8-15
Course of reaction without enzyme
EA without enzyme
EA with enzyme is lower
Reactants
Free energy
Course of reaction with enzyme
DG is unaffected by enzyme
Products
Progress of the reaction
42
Substrate Specificity of Enzymes

• The reactant that an enzyme acts on is called the
  enzymes 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

43
LE 8-16
Substrate
Active site
Enzyme-substrate complex
Enzyme
44
Catalysis in the Enzymes 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

45
LE 8-17
Substrates enter active site enzyme changes
shape so its active site embraces the substrates
(induced fit).
Substrates held in active site by
weak interactions, such as hydrogen bonds
and ionic bonds.

• Active site (and R groups of
• its 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
Enzyme-substrate complex
Active site is available for two
new substrate molecules.
Enzyme
Products are released.
Substrates are converted into products.
Products
46
Effects of Local Conditions on Enzyme Activity

• An enzymes activity can be affected by
• General environmental factors, such as
  temperature and pH
• Chemicals that specifically influence the enzyme

47
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

48
LE 8-18
Optimal temperature for typical human enzyme
Optimal temperature for enzyme of thermophilic
(heat-tolerant
bacteria)
Rate of reaction
0
20
40
60
80
100
Temperature (C)
Optimal temperature for two enzymes
Optimal pH for pepsin (stomach enzyme)
Optimal pH for trypsin (intestinal enzyme)
Rate of reaction
0
1
2
3
4
5
6
7
8
9
10
pH
Optimal pH for two enzymes
49
Cofactors

• Cofactors are nonprotein enzyme helpers
• Coenzymes are organic cofactors

50
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

51
LE 8-19
Substrate
A substrate can bind normally to the active site
of an enzyme.
Active site
Enzyme
Normal binding
A competitive inhibitor mimics the substrate,
competing for the active site.
Competitive inhibitor
Competitive inhibition
A noncompetitive inhibitor binds to the enzyme
away from the active site, altering
the conformation of the enzyme so that its active
site no longer functions.
Noncompetitive inhibitor
Noncompetitive inhibition
52
Concept 8.5 Regulation of enzyme activity helps
control metabolism

• Chemical chaos would result if a cells metabolic
  pathways were not tightly regulated
• To regulate metabolic pathways, the cell switches
  on or off the genes that encode specific enzymes

53
Allosteric Regulation of Enzymes

• Allosteric regulation is the term used to
  describe cases where a proteins function at one
  site is affected by binding of a regulatory
  molecule at another site
• Allosteric regulation may either inhibit or
  stimulate an enzymes activity

54
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

55
LE 8-20a
Allosteric activator stabilizes active form.
Allosteric enzyme with four subunits
Active site (one of four)
Regulatory site (one of four)
Activator
Active form
Stabilized active form
Oscillation
Allosteric inhibitor stabilizes inactive form.
Non- functional active site
Inhibitor
Stabilized inactive form
Inactive form
Allosteric activators and inhibitors
56

• 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

57
LE 8-20b
Binding of one substrate molecule to active site
of one subunit locks all subunits in active
conformation.
Substrate
Stabilized active form
Inactive form
Cooperativity another type of allosteric
activation
58
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

59
LE 8-21
Initial substrate (threonine)
Active site available
Threonine in active site
Enzyme 1 (threonine deaminase)
Isoleucine used up by cell
Intermediate A
Feedback inhibition
Enzyme 2
Active site of enzyme 1 cant bind theonine pathwa
y off
Intermediate B
Enzyme 3
Intermediate C
Isoleucine binds to allosteric site
Enzyme 4
Intermediate D
Enzyme 5
End product (isoleucine)
60
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

61
LE 8-22
Mitochondria, sites of cellular respiration
1 µm
62
Cells control chemical reactions by

• Regulating synthesis of enzymes
• Producing inactive forms and activating only when
  needed.