1. Chapter 8: An Introduction to Metabolism

2. Chapter 8: An Introduction to Metabolism
What is metabolism?
All of an organisms chemical processes
What are the different types of metabolism?
Catabolism – releases energy by breaking down complex molecules
Anabolism – use energy to build up complex molecules
Catabolic rxns – hydrolysis – break bonds
Anabolic rxns – dehydration – form bonds
How is metabolism regulated?
Enzymes
Enzyme 1
Enzyme 2
Enzyme 3 A B C D
Reaction 1
Reaction 2
Reaction 3
Starting molecule
Product

3. Chapter 8: An Introduction to Metabolism
4. What are the different forms of energy?
- Kinetic – energy from molecules in motion
- Potential – energy based on location or structure
- water behind a dam
- bonds in gas/oil/fats/starch
- Chemical energy – bio speak for potential energy from release in a catabolic rxn

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

5. Chapter 8: An Introduction to Metabolism
5. What are the 2 laws of thermodynamics?
- 1st law – Energy is constant. It can be transferred or transformed but it cannot be created or destroyed.
- 2nd law – Every transfer or transformation of energy increases the entropy (disorder) of the universe.
(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 cheetah’s movement in (b).
Second law of thermodynamics: Every energy transfer or transformation increases
the disorder (entropy) of the universe. For example, disorder is added to the cheetah’s
surroundings in the form of heat and the small molecules that are the by-products
of metabolism.
(b)
Chemical
energy
Heat
co2
H2O +

6. Chapter 8: An Introduction to Metabolism
What is the difference between exergonic & endergonic rxns?
- Exergonic – releases energy
- Endergonic – require energy
- Catabolic rxns – hydrolysis – break bonds – exergonic
- Anabolic rxns – dehydration – form bonds – endergonic
7. Where does the energy come from to drive rxns in the body?
- ATP CH –O O
CH2 H OH N C HC
NH2
Adenine
Ribose O– P
Phosphate groups

7. Chapter 8: An Introduction to Metabolism
8. How does ATP provide energy?
- hydrolysis of ATP P
Adenosine triphosphate (ATP)
H2O +
Energy
Inorganic phosphate
Adenosine diphosphate (ADP)
P i

8. Figure 8.10 Energy coupling using ATP hydrolysis
Endergonic reaction: ∆G is positive, reaction
is not spontaneous
∆G = +3.4 kcal/mol
Glu
∆G = –7.3 kcal/mol
ATP
H2O +
NH3
ADP
NH2
Glutamic
acid
Ammonia
Glutamine
Exergonic reaction: ∆ G is negative, reaction
is spontaneous P
Coupled reactions: Overall ∆G is negative;
together, reactions are spontaneous
∆G = –3.9 kcal/mol

9. Figure 8.11 How ATP drives cellular work+ P
Motor protein
P i
Protein moved
(a) Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ATP
Solute
P i
ADP
Solute transported
(b) Transport work: ATP phosphorylates transport proteins
Glu
NH3
NH2
(c) Chemical work: ATP phosphorylates key reactants
Reactants: Glutamic acid
and ammonia
Product (glutamine)
made

10. Figure 8.12 The ATP cycle ATP synthesis from ADP + P i requires energy
Energy for cellular work
(endergonic, energy-
consuming processes)
Energy from catabolism
(exergonic, energy yielding
processes)
ATP hydrolysis to
ADP + P i yields energy

11. Chapter 8: An Introduction to Metabolism
9. What is an enzyme?
- biological catalyst made of protein
10. How do enzymes work?
- lower energy of activation (EA)
- EA - energy reactants must absorb before the rxn can start

12. Figure 8.14 Energy profile of an exergonic reactionD B
Transition state
Products
Progress of the reaction
∆G < O
Reactants
Free energy EA
The reactants AB and CD must absorb
enough energy from the surroundings
to reach the unstable transition state,
where bonds can break.
Bonds break and new
bonds form, releasing
energy to the
surroundings.

13. Figure 8.15 The effect of enzymes on reaction rate.
Progress of the reaction
Products
Course of
reaction
without
enzyme
Reactants
with enzyme EA
EA with
is lower
∆G is unaffected
by enzyme
Free energy

14. Chapter 8: An Introduction to Metabolism
Some enzyme terms
- substrate – what the enzyme works on – substrate specific
- active site – where the substrate binds to the enzyme
- induced fit – molecular handshake – when the enzyme binds to the substrate, it wraps around the substrate
Substrate
Active site
Enzyme
(a)
(b)
Enzyme- substrate
complex

15. Figure 8.17 The active site and catalytic cycle of an enzyme
1 Substrates enter active site; enzyme
changes shape so its active site
embraces the substrates (induced fit).
Substrates
Products
Enzyme
Enzyme-substrate
complex
5 Products are
Released.
2 Substrates held in
active site by weak
interactions, such as
hydrogen bonds and
ionic bonds.
3 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.
4 Substrates are
Converted into
Products.
6 Active site
is available for
two new substrate
molecules.

16. Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
- temperature
- pH
Optimal pH for two enzymes
Rate of reaction 20 40 60 80
100
Temperature (Cº)
(a) Optimal temperature for two enzymes
(b) Optimal pH for two enzymes pH
Optimal temperature for
typical human enzyme
enzyme of thermophilic
Optimal pH for pepsin
(stomach enzyme)
Optimal pH
for trypsin
(intestinal
enzyme) 1 2 3 4 5 6 7 8 9 10
(heat-tolerant)
bacteria

17. Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
- temperature
- pH
- cofactors – non-protein helpers of enzyme activity (Zn, Fe, Cu)
- coenzymes (vitamins)
- inhibitors
- competitive – compete w/ substrate for active site
- non-competitive (allosteric) – bind remotely changing enzyme shape & inhibiting activity

18. Figure 8.19 Inhibition of enzyme activity
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.
Competitive
inhibitor
(a)
Normal binding
(b) Competitive inhibition
A substrate can
bind normally to the
active site of an
enzyme.
A competitive
inhibitor mimics the
substrate, competing
for the active site.
Substrate
Active site
Enzyme
Noncompetitive inhibitor
(c) Noncompetitive inhibition

19. Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
13. How are enzymes regulated?
- allosteric inhibitors
- allosteric activators
Stabilized inactive form
Allosteric activater stabilizes active from
Allosteric enyzme with four subunits
Active site (one of four)
Regulatory site (one of four)
Active form
Activator
Stabilized active form
Allosteric inhibiter stabilizes inactive form
Inhibitor
Inactive form
Non- functional active site
(a) Allosteric activators and inhibitors. In the cell, activators and inhibitors dissociate when at low concentrations. The enzyme can then oscillate again.
Oscillation

20. Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
13. How are enzymes regulated?
- allosteric inhibitors
- allosteric activators
- cooperativity
Binding of one substrate molecule to active site of one subunit locks all subunits in active conformation.
Substrate
Inactive form
Stabilized active form
(b) Cooperativity: another type of allosteric activation. Note that the inactive form shown on the left oscillates back and forth with the active form when the active form is not stabilized by substrate.

21. Chapter 8: An Introduction to Metabolism
12. What affects enzyme activity?
13. How are enzymes regulated?
- allosteric inhibitors
- allosteric activators
- cooperativity
- feedback inhibition
- compartmentalization in the cell
Active site available
Isoleucine used up by cell
Feedback inhibition
Isoleucine binds to allosteric site
Active site of enzyme 1 no longer binds threonine; pathway is switched off
Initial substrate (threonine)
Threonine in active site
Enzyme 1 (threonine deaminase)
Intermediate A
Intermediate B
Intermediate C
Intermediate D
Enzyme 2
Enzyme 3
Enzyme 4
Enzyme 5
End product (isoleucine)