1. Introduction to Metabolism

2. Metabolism is the sum of an organism’s chemical reactions
Metabolism is an emergent property of life that arises from interactions between molecules within the cell

3. BIOCHEMICAL PATHWAY VIDEO
A metabolic pathway begins with a specific molecule and ends with a product
The product of one reaction is substrate of the next
Each step is catalyzed by a specific enzyme
BIOCHEMICAL PATHWAY VIDEO

4. ENZYMES THAT WORK TOGETHER IN A PATHWAY CAN BE
Concentrated in specific location
Covalently bound in complex
Soluble with free floating
intermediates
Attached to a membrane in sequence

5. CATABOLIC PATHWAY (CATABOLISM) Release of energy by the breakdown of complex molecules to simpler compounds EX: digestive enzymes break down food ANABOLIC PATHWAY (ANABOLISM) consumes energy to build complicated molecules from simpler ones EX: linking amino acids to form proteins

6. Krebs Cycle connects the catabolic and anabolic pathways

7. Forms of Energy ENERGY = capacity to cause change
Energy exists in various forms (some of which can perform work)
Energy can be converted from one form to another

8. KINETIC ENERGY – energy associated with motion
HEAT (thermal energy) is kinetic energy associated with random movement of atoms or molecules
POTENTIAL ENERGY = energy that matter possesses because of its location or structure
CHEMICAL energy is potential energy available for release in a chemical reaction

9. Diving converts
potential energy to
kinetic energy.
On the platform, the diver has
more potential energy.
In the water, the diver has less potential energy.
Climbing up converts kinetic energy of muscle movement to potential energy.

10. THERMODYNAMICS = the study of energy transformations
CLOSED system (EX: liquid in a thermos) = isolated from its surroundings
OPEN system energy + matter can be transferred between the system and its surroundings
Organisms are open systems

11. The First Law of Thermodynamics
= energy of the universe is constant
Energy can be transferred and transformed
Energy cannot be created or destroyed
The first law is also called the principle of CONSERVATION OF ENERGY

12. The Second Law of Thermodynamics
During every energy transfer or transformation
entropy (disorder) of the universe INCREASES
some energy is unusable, often lost as heat

13. ORGANISMS are energy TRANSFORMERS!
Second law of thermodynamics
First law of thermodynamics
Chemical
energy
Heat
CO2
H2O
ORGANISMS are energy TRANSFORMERS!
Spontaneous processes occur without energy input; they can happen quickly or slowly
For a process to occur without energy input, it must increase the entropy of the universe

14. Free-Energy Change (G) can help tell which reactions will happen
∆G = change in free energy ∆H = change in total energy (enthalpy)
∆S = change in entropy T = temperature
∆G = ∆H - T∆S
Only processes with a negative ∆G are spontaneous
Spontaneous processes can be harnessed to perform work

15. Free Energy, Stability, and Equilibrium
Free Energy- a measure of a systems instability
Unstable systems (higher G) tend to change in such a way that they become more stable (lower G)
A process is spontaneous and can perform work only when it is moving toward equilibrium
Equilibrium is a state of maximum stability

16. More free energy (higher G) Less stable Greater work capacity
In a spontaneous change
The free energy of the system
decreases (∆G < 0)
The system becomes more
stable
The released free energy can
be harnessed to do work
Figure 8.5 The relationship of free energy to stability, work capacity, and spontaneous change
Less free energy (lower G)
More stable
Less work capacity

17. Exergonic and Endergonic Reactions in Metabolism
EXERGONIC reactions (energy outward) (- ∆G)
Release energy
are spontaneous

18. Exergonic and Endergonic Reactions in Metabolism
ENDERGONIC reactions (energy inward) (+ ∆G)
Absorb energy from their surroundings
are non-spontaneous

19. Mechanical Transport Chemical
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
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

20. ATP provides energy for cellular functions
ATP (adenosine triphosphate) is the cell’s renewable and reusable energy shuttle
ATP provides energy for cellular functions
Energy to charge ATP comes from catabolic reactions
Adenine
Phosphate groups
Ribose

21. Adenosine triphosphate (ATP)+ P P +
Energy i
Inorganic phosphate
Adenosine diphosphate (ADP)

22. Energy for cellular work provided by the loss of phosphate from ATP
Energy from catabolism
(used to charge up ADP into ATP
ADP + P i

23. Glutamic acid Ammonia Glutamine ATP H2O ADP
Endergonic reaction:
DG is positive, reaction is not spontaneous
NH2 +
NH3
DG = +3.4 kcal/mol
Glu
Glu
Glutamic
acid
Ammonia
Glutamine
Exergonic reaction:
DG is negative, reaction is spontaneous
ATP +
H2O
ADP P +
DG = –7.3 kcal/mol i
Coupled reactions:
Overall DG is negative;
Together, reactions are spontaneous
DG = –3.9 kcal/mol

24. Reactants: Glutamic acidP i P
Motor protein
Protein moved
Mechanical work: ATP phosphorylates motor proteins
Membrane
protein
ADP
ATP + P i P P i
Solute
Solute transported
Transport work: ATP phosphorylates transport proteins P
NH2 +
NH3
Glu + P i
Glu
Reactants: Glutamic acid
and ammonia
Product (glutamine)
made
Chemical work: ATP phosphorylates key reactants

25. Every chemical reaction between molecules involves
bond breaking and bond forming
ACTIVATION ENERGY = amount of energy required to get chemical reaction started
Activation energy is often supplied in the form
of heat from the surroundings
Free energy animation
IT’S LIKE PUSHING A
SNOWBALL UP A HILL . . .
Once you get it up there,
it can roll down by itself

26. The Activation Energy BarrierD
Transition state A B EA
Free energy C D
Reactants A B
DG < O C D
Products
Progress of the reaction

27. CATALYST = a chemical agent that speeds up a reaction without being consumed by the reaction ENZYMES = biological catalysts Most enzymes are PROTEINS Exception = ribozymes (RNA)

28. ENZYMES work by LOWERING ACTIVATION ENERGY;
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
ENZYMES work by LOWERING ACTIVATION ENERGY;

29. ENZYMES LOWER ACTIVATION ENERGY BY:
Orienting substrates correctly
Straining substrate bonds
Providing a favorable microenvironment
Enzymes change ACTIVATION ENERGY but NOT energy of REACTANTS or PRODUCTS

30. ENZYMES Most are proteins Lower activation energy Specific
Shape determines function
Re-usable
Unchanged by reaction

31. The REACTANT that an enzyme acts on = SUBSTRATE
Enzyme + substrate = ENZYME-SUBSTRATE COMPLEX
Region on the enzyme where the substrate binds = ACTIVE SITE
Substrate held in active site by WEAK interactions (ie. hydrogen and ionic bonds)

32. TWO MODELS PROPOSED
LOCK & KEY Active site on enzyme fits substrate exactly
INDUCED FIT Binding of substrate causes change in active site so it fits substrate more closely

33. Enzyme Activity can be affected by:
General environmental factors, such as temperature, pH, salt concentration, etc.
Chemicals that specifically influence the enzyme
See a movie
Choose narrated

34. TEMPERATURE & ENZYME ACTIVITY
Each enzyme has an optimal temperature at which it can function (Usually near body temp)

35. Increasing temperature increases the rate of an
enzyme-catalyzed reaction up to a point.
Above a certain temperature, activity begins to
decline because the enzyme begins to denature.

36. pH and ENZYME ACTIVITY Each enzyme has an optimal pH at which it can function

37. COFACTORS = non-protein enzyme helpers
EX: Zinc, iron, copper
COENZYMES = organic enzyme helpers
Ex: vitamins

38. SUBSTRATE CONCENTRATION & ENZYME ACTIVITY←
V MAX
Adding substrate increases activity up to a point

39. REGULATION OF ENZYME PATHWAYS
GENE REGULATION cell switches on or off the genes that code for specific enzymes

40. REGULATION OF ENZYME PATHWAYS
FEEDBACK INHIBITION end product of a pathway interacts with and “turns off” an enzyme earlier in pathway
prevents a cell from wasting chemical resources by synthesizing more product than is needed
FEEDBACK INHIBITION

41. NEGATIVE FEEDBACK
An accumulation of an end product slows the process that produces that product B A C D
Enzyme 1
Enzyme 2
Enzyme 3
Negative feedback
Example: sugar breakdown generates ATP; excess ATP
inhibits an enzyme near the beginning of the pathway

42. POSITIVE FEEDBACK (less common)
The end product speeds up production W X Y Z
Enzyme 4
Enzyme 5
Enzyme 6
Positive feedback
EXAMPLE: Chemicals released by platelets that accumulate
at injury site, attract MORE platelets to the site.

43. REGULATION OF ENZYME ACTIVITY
ALLOSTERIC REGULATION protein’s function at one site is affected by binding of a regulatory molecule at another site
Allosteric regulation can inhibit or stimulate an enzyme’s activity
Allosteric enzyme inhibition

44. SOME ALLOSTERIC ENZYMES HAVE MULTIPLE SUBUNITS
Each enzyme has active and inactive forms
The binding of an ACTIVATOR stabilizes the active form
The binding of an INHIBITOR stabilizes the inactive form

45. Binding of one substrate molecule to
active site of one subunit locks all
subunits in active conformation.
Substrate
Inactive form
Stabilized active form
COOPERATIVITY another type of allosteric activation

46. COOPERATIVITY = form of allosteric regulation that can amplify
enzyme activity
Binding of one substrate to active site of one subunit locks all subunits in active conformation

47. Enzyme Inhibitors
COMPETITIVE inhibitor REVERSIBLE; Mimics substrate and competes with substrate for active site on enzyme
ENZYME ANIMATION

48. Enzyme Inhibitors
NONCOMPETITIVE inhibitors bind to another part of an enzyme, causing the enzyme to change shape and making the active site less effective
ENZYME ANIMATION