Unformatted text preview: CHEM 350: Introduction to Biological Chemistry
Brian Lee, Ph.D.
Ofﬁce: Neckers 146G or 324
Ho urs: 9:30am to 10:30am or by appointment
Textbook (required, U.S. edition only)
Fundamentals of Biochemistry, 3rd Ed., Voet, Voet & Pratt.
Study Guide (recommended)
Student Companion to Fundamentals of Biochemistry, 3rd Ed.
Tuesday 6:30 to 7:30 pm in Neckers 218
Thursday 5:00 to 6:00 pm in Neckers 410 Announcements
Undergraduate Research Opportunities
Research for credit (such as CHEM 396 or CHEM 496)
Student worker ($8.00 per hour) (http://www.siu.edu/~fao/jobs/)
Undergraduate Assistantships (http://www.siu.edu/~fao/jobs/)
McNair Scholars Program (http://www.siu.edu/~mcnair)
REACH Awards Competition (http://www.siu.edu/~reach/)
Summer Research Experiences for Undergraduates (REU)
Deadline for SIUC REU Program is TODAY
For other REU programs, search the National Science Foundation site:
Students must contact the individual sites for information and
application materials. NSF does not have application materials and does
not select student participants. A contact person and contact
information is listed for each site. Assignments
Read Chapter 12 Enzyme Kinetics
Chapter 12 Problems
Student Companion site for Voet, Voet & Pratt
http://bcs.wiley.com/he-bcs/Books?action=index&bcsId=4274&itemId=0470129301 Third Midterm Exam, Wednesday March 28th
Tuesday 6:30 to 7:30 pm in Neckers 218
Thursday 5:00 to 6:00 pm in Neckers 410 Cofactors
Enzymes may require cofactors for catalysis.
A Cofactor is not consumed by the catalytic reaction.
The Cofactor may be modiﬁed, but is always regenerated
(sometimes by a secondary or accessory enzyme). Apoenzyme (inactive) + Cofactor = Holoenzyme (active)
- Cofactors usually participate in catalysis and are often
mo diﬁed during the reaction.
- Cofactors are returned to initial state before continuing
catalysis. Cofactors: Metals
Metal ions participate
in the catalytic reaction.
The multiple oxidation
states of metal ions can
be utilized in oxidationreduction reactions. Cofactors: Coenzymes
Apoenzyme (inactive) + Cofactor = Holoenzyme (active)
Coenzymes may be cosubstrates for the enzyme reaction.
Tightly bound coenzymes are called prosthetic groups.
Vitamins are often precursors to coenzymes. Vitamins related to disease and essential functions in cells
thiamine B1 (beriberi neurodegenerative) required for
carbohydrate metabolism – deﬁcient in processed white rice
riboﬂavin B2 required for electron transfer reactions
niacin B3 (pellagra) common in rural South corn-rich diet,
treating corn with lime, Ca(OH)2 (to make tortillas) allows
niacin to be absorbed from corn
pyridoxine B6 required for amino acid metabolism
biotin B7 required for fatty acid metabolism
cobalamin B12 (pernicious anemia) required for nucleotide and
amino acid metabolism, directly involved in folate synthesis
folic acid B9 (megaloblastic anemia during pregnancy)
required for amino acid metabolism Coenzyme must be regenerated
by another reaction, which may
require another enzyme.
oxidation in glycolysis by GAPDH) Thermodynamics Review
Gibbs Free Energy
• Biochemical standard free energy
if G < 0, then spontaneous
for a chemical reaction:
A + B -> C + D [C][D]
G = G° + RT ln
[A][B] At equilibrium, G = 0
G°’ = -RT ln K’eq
Under standard conditions
K’eq = 10- G°’/5.7kJ/mol when Keq < 1
then G > 0 For example: DHAP -> GAP
K’eq = GAP/DHAP = 0.0475
G°’ = -RT ln K’eq
= 7.53 kJ/mol
isomerase What if?
[GAP] = 3 μM
[DHAP] = 200 μM
[GAP]/[DHAP] = 0.0150
G= G°’ + RT ln [GAP]/
[DHAP] G = 7.53 - 10.42 = -2.89 kJ/mol What does Gibbs Free Energy tell us?
G compares enthalpy and entropy of the system.
If G is negative, the reaction is spontaneous.
A spontaneous reaction may proceed, but at what rate?
Thermodynamics tells us nothing about the reaction rate.
A reaction may be spontaneous ...
... but so slow, that it never happens.
Problem: How do we get from Reactant to Product? Transition State Theory gives us the pathway between
Reactant and Product using a few assumptions:
1) The rate of product formation is directly related
to the population of the transition state.
2) There is a rapid equilibrium between reactant and
The energy difference
between transition state and
reactant is the Gibbs free
energy of activation, G .
Note: Gibbs free energy for
the reaction, G°’, is the
difference between product
and reactant free energy. Transition State Theory
Transition state theory allows us to
relate reaction rates (kinetics) to
Gibbs Free Energy (thermodynamics)
Given the Chemical Reaction
A <-> X‡ -> P
Assume that the rate of product
formation is directly related to the
concentration of transition state:
VP = k[X‡]
Assume rapid equilibrium
A <-> X‡ Deﬁne equilibrium constant
K‡ = [X‡]/[A]
and Gibbs Free Energy
G‡ = -RT ln K‡ Rearrange and solve for X :
- G‡/RT = ln K‡
e- G‡/RT = K‡
e- G‡/RT = [X‡]/[A]
[A] e- G‡/RT = [X‡]
Reaction rate (product formation):
V = k[X‡]
Combine rate and G relations
V = k[A] e- G‡/RT
Maximal reaction rates are limited
by the vibration of chemical bonds.
Bond vibration rate: kbT/h = 6.2 x 1012 s-1 at 25°C Replace k with kbT/h
V = kbT/h [A] e- G‡/RT Transition State Theory
V = kbT/h [A] e- G‡/RT V is the reaction rate
[A] is substrate concentration
G‡ is free energy of activation
This is remarkable similar to the empirically derived
Arrhenius Equation: k = Ae E a RT k is the reaction rate
A is the collision frequency factor (related to concentration)
Ea is the activation energy
The Rate of the Reaction is inversely and exponentially
proportional to the Gibbs Free Energy of Activation. Enzymes and Free Energy
• Enzymes have no effect on equilibrium
– Enzymes cannot change G°’ • Enzymes accelerate the rate of a
chemical reaction toward equilibrium
• Given that K’eq = kforward/kreverse
• Enzymes increase both the forward
and reverse reaction rates
• Reaction rates can be related to
Gibbs free energy of activation = G‡ Activation Energy of an Enzymatic Reaction
E+S ES ES‡ EP E+P Transition state intermediate, ES‡ G‡cat Enzymes lower the activation energy by stabilizing S‡ G‡cat How does an enzyme
reduced the energy of
the transition state S‡
an d accelerate the rate
of a reaction? Substrate binding
Transition state binding
Lock and key versus Induced ﬁt Organic Chemistry Review
Electron Pushing The curved arrows are electron pairs which move from
an electron rich atom toward an electron deﬁcient atom.
The number of bonds follows the standard rules of
chemistry (Lewis structures and Valence Bond Theory). ...
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