HOMEWORK 11/3: Take notes on the following slides: 23 to 39 http://ag.ansc.purdue.edu/sheep/ansc442/Semprojs/2003/spiderlamb/eatsheep.gif
http://www.gifs.net

• 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 http://www.encognitive.com/images/metabolic-pathways.png

A metabolic pathway begins with a specific molecule and ends with a product
• Each step is catalyzed by a specific enzyme
BIOCHEMICAL PATHWAY
VIDEO

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

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 http://www.sciencelearn.org.nz/var/sciencelearn/storage/images/contexts/nanoscience/sci_media/images/chemical_reactions_involve_making_new_combinat ions/53823-2-eng-NZ/chemical_reactions_involve_making_new_combinations_full_size_landscape.jpg

Krebs Cycle connects the catabolic and anabolic pathways http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/I/IntermediaryMetabolism.html

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

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

On the platform, the 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, the diver has less potential energy.

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 http://ag.ansc.purdue.edu/sheep/ansc442/Semprojs/2003/spiderlamb/eatsheep.gif

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 http://www.pxleyes.com/photoshop-picture/4a3b747566555/remote-control.html
http://www.suncowboy.com/solar101.php

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 http://hyperphysics.phy-astr.gsu.edu/hbase/therm/entrop.html
http://www.janebluestein.com/articles/whatswrong.html

First law of thermodynamics
Chemical energy
Second law of thermodynamics
Heat
CO
2
ORGANISMS are energy TRANSFORMERS!
H
2
O
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


∆G = change in free energy
∆H = change in total energy (enthalpy) or change
∆S = entropy
T = temperature
∆G = ∆H - T∆S
• Only processes with a negative ∆G are spontaneous
• Spontaneous processes can be harnessed to perform work

Exergonic and Endergonic Reactions in Metabolism
• EXERGONIC reactions
(- ∆G)
• Release energy
• are spontaneous
ENDERGONIC reactions
(+ ∆G)
• Absorb energy from their surroundings
• are non-spontaneous

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

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

LE 8-9
P P P
Adenosine triphosphate (ATP)
H
2
O
P i
+ P P
Inorganic phosphate Adenosine diphosphate (ADP)
+ Energy

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

Endergonic reaction:
DG is positive, reaction is not spontaneous
NH
2
Glu
Glutamic acid
+ NH
3
Ammonia
Glu
Glutamine
Exergonic reaction:
DG is negative, reaction is spontaneous
ATP + H
2
O ADP +
P i
Coupled reactions:
Overall DG is negative;
Together, reactions are spontaneous

G = +3.4 kcal/mol


G =
G =
–7.3 kcal/mol
–3.9 kcal/mol

LE 8-11
ATP
P i
P
Motor protein Protein moved
Mechanical work: ATP phosphorylates motor proteins
Membrane protein
P P i
Solute Solute transported
Transport work: ATP phosphorylates transport proteins
P
Glu
+
NH
3
NH
2
Glu
+ P i
Reactants: Glutamic acid and ammonia
Product (glutamine) made
Chemical work: ATP phosphorylates key reactants
ADP
+
P i

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 http://www.chuckwagondiner.com/art/matches.jpg
http://plato.acadiau.ca/COURSES/comm/g5/Fire_Animation.gif

LE 8-14
A B
C D
Reactants
The Activation Energy Barrier
A B
C D
Transition state
E
A
A B
C D
Products

G < O
Progress of the reaction

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) Ch 17 & 26

Course of reaction without enzyme
E
A without enzyme
E
A with enzyme is lower
Reactants
Course of reaction with enzyme

G is unaffected by enzyme
Products
Progress of the reaction
ENZYMES work by LOWERING ACTIVATION ENERGY ;

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 http://sarahssureshots.wikispaces.com/Focus+on+Proteins http://www.ac-montpellier.fr/sections/personnelsen/ressources-pedagogiques/education-artistique/consultation-avis-du

•
•
•
•
•
•
Image from: http://www.hillstrath.on.ca/moffatt/bio3a/digestive/enzanim.htm

• 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 )

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 http://www.grand-illusions.com/images/articles/toyshop/trick_lock/mainimage.jpg
http://commons.wikimedia.org/wiki/File:Induced_fit_diagram.png

Enzyme Activity can be affected by:
– General environmental factors, such as temperature, pH, salt concentration, etc.
– Chemicals that specifically influence the enzyme
Choose narrated http://www.desktopfotos.de/Downloads/melt_cd.jpg
http://www.nealbrownstudio.com/adm/photo/163_nb_fried_egg.jpg

TEMPERATURE & ENZYME ACTIVITY
Each enzyme has an optimal temperature at which it can function (Usually near body temp) http://www.animated-gifs.eu/meteo-thermometers/001.htm

http://www.uic.edu/classes/bios/bios100/lectures/chemistry.htm
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.

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

CO FACTORS
= non-protein enzyme helpers
• EX: Zinc, iron, copper http://www.wissensdrang.com/media/wis9r.gif
CO ENZYMES
= organic enzyme helpers
• Ex: vitamins http://www.elmhurst.edu/~chm/vchembook/595FADcoq.html

← V
MAX
Adding substrate increases activity up to a point

• GENE REGULATION cell switches on or off the genes that code for specific enzymes

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

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

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

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 http://bio.winona.edu/berg/ANIMTNS/allostan.gif

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

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

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

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

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