Download Week 2

Intermediary Metabolism
How your body uses that Big Mac
The Laws of Thermodynamics
In every physical or chemical change, the
total amount of energy in the universe
remains constant, although the form of the
energy may change. That is, energy can be
changed from one form to another, but can
never be destroyed.
Intermediary metabolism is the process by
which chemical energy is captured and
transformed for later use in a variety of
energy-utilizing processes (“work”).
Energy flows through the Biosphere
Thermodynamics and reactions
• Energy out = Energy In – Energy Stored
• ∆E=Eproducts-Ereactants
• C6H12O6+6O2↔6CO2+6H2O ∆H=-673kcal/mole
(here “H” is “enthalpy”, or heat content: H=E+PV)
GibbsFree Energy: ∆G=∆H-T∆S.
(here “S” is entropy, or disorganization, and T is the temperature)
Reactions involving a decrease in free energy
(ΔG<0) are spontaneous. Otherwise the reaction
will not go (as written).
A mole is the
gram molecular
weight of a
compound. For
glucose it is
C 6*12=72
H 12*1=12
O 6*16=72
TOTAL 156 gm
(5.5 oz)
A calorie is the
amount of heat
that will raise
one gram of
water 1 degree
centigrade. A
dietary calorie is
1000 calories, or
one kcal.
Equilibrium and ∆G
The equilibrium constant is the ratio of product concentration to
reactant concentration at equilibrium:
 product eq
K eq 
 reactant eq
ΔG0 is the “Standard Free Energy” of a reaction ( at equilibrium): ∆𝐺 𝑜 = −𝑅𝑇𝑙𝑛𝐾𝑒𝑞
The actual ΔG of a reaction is the difference between equilibrium and the
actual concentration of the reactants:
[𝑝𝑟𝑜𝑑𝑢𝑐𝑡]
∆𝐺 = ∆𝐺 + 𝑅𝑇𝑙𝑛
[𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡]
𝑜
Summary: Thermodynamics of Reactions
1. The direction (A→B or B→A) and energy (yield or need thereof) of a
reaction is:
1. Independent of the path (mechanism) of the reaction
2. Completely dependent on the concentration of the products and reactants
2. The rate of a reaction is:
1. Independent of the energy lost or gained in the reaction
2. Completely dependent on the path (mechanism) of the reaction.
A biological example:
• Consider the conversion of glucose-6-phosphate to fructose-6-phosphate
(Keq=0.5).
• If you start with equimolar concentrations of G-6-P and F-6-P and allow the
reaction to go, you will wind up at equilibrium with twice as much G6P as
F6P (i.e., 1/3 is converted). Thus,
F6P
G6P
𝑒𝑞
𝑒𝑞
1
= = 0.5 = Keq
2
A biological example (cont’d)
• The standard free energy thus is:
∆𝐺 𝑜 = −𝑅𝑇𝑙𝑛𝐾𝑒𝑞
=−(1.487cal•˚K-1mol-1)(298˚K) ln 0.5
=−(592cal•mol-1)(−0.693)
=+410cal•mol-1
Here, ΔG is positive and thus the reaction will not go
as written, i.e., G6P will not form F6P.
BUT: this is a vital reaction and goes on all the time in
your body!! How can this be??
A biological example (cont’d)
• The solution: remember that the ΔG of a reaction depends on how far
the concentrations of the reactants are from their equilibrium
concentrations.
• So to beat the game, your body utilizes a subsequent reaction that
rapidly consumes the F6P as it is produced, keeping its concentration
extremely low.
• Here’s how it works:
A biological example (cont’d)
• In human red blood cells, the concentrations are:
• [glucose-6-phosphate]=83mM
• [fructose-6-phosphate]=14mM
[𝑝𝑟𝑜𝑑𝑢𝑐𝑡]
∆𝐺 =
+ 𝑅𝑇𝑙𝑛
[𝑟𝑒𝑎𝑐𝑡𝑎𝑛𝑡]
14
−1
= 410𝑐𝑎𝑙 ∙ 𝑚𝑜𝑙 + 𝑅𝑇𝑙𝑛 𝑐𝑎𝑙 ∙ 𝑚𝑜𝑙 −1
83
∆𝐺 𝑜
= 410𝑐𝑎𝑙 ∙ 𝑚𝑜𝑙 −1 − 1053𝑐𝑎𝑙𝑚𝑜𝑙 −1
= −643𝑐𝑎𝑙 ∙ 𝑚𝑜𝑙 −1
Which is a rather large negative ΔG, ,meaning the reaction goes
spontaneously and nearly to completion, and you live to come to CLS
another day!!
Energy of Activation
Spontaneity (ΔG) tells us that a reaction can go, but not whether or not it will go.
Heat and Catalysts Speed Up
Reactions by helping the
reactants overcome the
energy of activation barrier.
Heat gives the reactants
more energy, while catalysts
lower the barrier.
Redox Reactions
• In a redox reaction one
compound is reduced (gains
electrons) while its partner is
oxidized (loses electrons)
Redox reactions can be chained
• A substance such as NAD can act
as an electron carrier, carrying
electrons from one reaction to
another.
• The NAD can be a mobile or a
membrane-bound carrier.
Conclusions*
•By altering the concentrations of reactants and products,
living cells can make unfavorable reactions go.
•Catalysts speed up reactions by lowering the energy of
activation.
•Note that catalysts DO NOT change ∆G: they
cannot make an unfavorable reaction
favorable!
•Energy produced by one reaction can be used by another
reaction (as in redox reactions)
*(take a breath; we’re done with p-chem for a while)
ATP: currency of the cell

 ADP  Pi
ATP  H2O 


enz
G  7.3kcal
Gcell  12.5kcal
o'
Intermediary Metabolism: An overview
Glycolysis: details
Budget: 1 glucose→2 pyruvate; 4 ATP produced, two used (net +2); 2 NADH+ produced.
Some energetics of glycolysis
• Glucose: C6H12O6+6O2→6CO2+6H2O ΔG0’ =-686kcal/mole
• Pyruvate: C3H6O2+3O2→3CO2+3H2O ΔG0’ =-319.5kcal/mole
• -686-(2x(-319.5)) = 47kcal yield for glycolysis
• 2 ATP @ 12.5 kcal/mole = 25 kcal out of 47 kcal = 50% efficiency
• Overall efficiency of glucose to ATP: 25/686= 3%
Regulation of Glycolysis/Gluconeogenesis
•Feedback Regulation
•ATP and other products (NADH)
•Hormonal Regulation
•Insulin
•Glucagon
Anaerobic vs. aerobic metabolism
So far we’ve used no oxygen. This is like muscles under
stress. But what if there is oxygen? Then we can burn the
pyruvate for energy in the Kreb’s (citric acid, TCA) cycle.
After Glycolysis, the TCA cycle in the matrix
of the mitochondria takes over
It’s called a
“cycle” for a
good reason
Budget:
One glucose produces:
2 ATP (from glycolysis)
8 NADH+H+ (2 from
glycolysis)
2 FADH2
2 GTP (=2 ATP)
6 CO2
But we still haven’t used any
oxygen!
Glycolysis and the TCA are versatile
What happens next??
Energy from “oxidative phosphorylation”
• A process to make ATP (“phosphorylation”) using oxygen.
• It uses the Electron Transport Chain (ETC) in the mitochondria
• The ETC is a series of redox reactions whose function it is to accept
electrons from the NADH and FADH from glycolysis and the TCA (thus
oxidizing and restoring them) and transfer those electrons to an
acceptor (reducing it)
• The ultimate acceptor is oxygen, which becomes reduced to water
(H2O).
The electron transport chain, like the TCA,
takes place in the mitochondria
But now the scene of
action shifts to the
inner membrane
rather than the matrix.
Let’s take a first look:
The Electron Transport System
Formation
ATP:
Transfer
ofof
electrons:
Transfer
of
Hydrogens:
The pump uses the proton gradient we just
made.
In most
places in the
body the
pump uses
ATP to form
proton
gradients
Summation
Substance
Source
# produced
ATP value
ATP
Glycolysis
2
2
TCA
2 (from GTP) 2
Glycolysis
2
6
TCA
6
18
TCA
2
4
NADH+H+
FADH2
TOTAL
32
32 ATP x 7.3kcal/ATP= 233.6 kcal out of 673 available= 35% efficiency
A gasoline engine is only about 25%
efficient!
What do you do when there’s no oxygen?
Recycling the lactate
Glycolysis
Gluconeogenisis
Nonshivering thermogenesis
Comparison of sugar and fat:
• A. Net products from oxidation of one mole of glucose (180 grams)
• 34 moles ATP
• 0.17 moles/gram
• B. Net products from oxidation of one mole of palmitate, a fatty acid
(256 grams)
• 93 ATP
• 0.36 moles/gram
The bottom line is that fat is a much better storage form for
energy than is glucose.
Organ
Specialization:
The Absorptive
Phase
The
Postabsorptive
Phase
Protein
pools
Carbohydrate
and Fat pools
Production and utilization of glucose