BIOC 2300 Lecture 19: BIOC 2300 - Lecture 19
6 Sep 2019
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BIOC 2300 – Lecture 19 March 8, 2019 Metabolic Flux
• Thermodynamics continued:
o How can an endergonic reaction become possible?
o Role of ATP as energy currency
• Directionality: Many pathways are overall reversible, but at any given time, only one direction is
active.
o How is directionality achieved? How does the cell avoid futile cycles? How does ATP act as an
energy currency?
Flux – is the rate of the overall pathway, describes how many molecules of substrate are converted to
product
Le Chatelier’s Principle
• Equilibrium = most stable state.
• Disturbances in the equilibrium => The system
moves back to equilibrium.
• Disturbances: Removal or addition of reactant or
product, Changes in temperature or pressure
• If a product is continuously removed, a reaction can keep going towards products
When you consider the reaction as a population of molecules that is sequentially reacting (A -> B), this would be
the forward reaction. Even if B has a lower free energy than A, then the equilibrium is even lower because the
entropy is lower for a mixture of two molecules. We have this equilibrium state, which is a characteristic of the
reaction or of the reactant components A and B. Thus, the equilibrium is characterized by certain ratios of A + B. If
you disturb the equilibrium, the system will strive to go back into the equilibrium, such as changes in temperature
or pressure. In this case, we are concern with the removal or the addition of reactant or products which is more
likely to occur in a cell. For example, in the upper example, you add a more A (product), the reaction will move
back to its equilibrium. If there is a reversible reaction between A and B, such that B can be secreted from the cell,
the reaction would readjust to return to equilibrium.
Recap: Free Energy Change in Exergonic and Endergonic Reactions
Exergonic reaction characterized by a
higher free energy of the reactant than of
the products. During the conversion of
reactant of products, you would go
through this equilibrium. If the
equilibrium is to the right of the
equimolar state, the reaction is
exergonic, favoring the formation of
products.
If you have an endergonic reaction, such
that your reactants have lower free energy than your products, this reaction have a positive ∆G. There
needs to be energy input. For an endergonic reaction, there is an unfavorable reaction and the Keq is
smaller than 1 because you have less products than reactants at equilibrium.
Unfavourable Reactions Require Energy to Occur
Glucose phosphorylation
• Glucose phosphorylation is a highly unfavorable reaction
• But it is still happening! How?
Thermodynamic unfavorable reactions still occur so how does this happen? One example of a highly
unfavorable reaction is glucose phosphorylation. Glucose phosphorylation is central to any glucose
metabolism. It is the first step of any glucose metabolism in the cell. This is where ATP as an energy
currency comes in.
Coupled Reactions
• Endergonic processes are often coupled to ATP
hydrolysis.
• Together, the coupled reactions are favourable and
possible.
• Cleavage of phosphoanhydride bonds yields energy
to drive unfavorable reactions.
There is the adenosine group and 3 phosphate group if
it is a ATP. Two of those bonds are phosphoanhydride
bonds. There is also an phosphodiester bond between
carbon and the phosphate groups. Between the
phosphates, they are phosphoanhydride bonds, which are cleaved to result in the exergonic reactions.
Glucose Phosphorylation
1. Glucose phosphorylation: A highly unfavorable reaction
2. ATP Hydrolysis: A highly favorable reaction
If glucose phosphorylation is coupled to ATP hydrolysis, the overall ∆G is negative and the reaction is
exergonic.
ATP Hydrolysis
• ATP hydrolysis provides the energy
for glucose phosphorylation.
• The ΔG0' values for each reaction
are added to give the ΔG0' value
for the coupled reaction.
To get to the ∆G of the net reaction,
you add up the ∆G values for each
reaction that is coupled. Even with
energy investment from ATP hydrolysis, this is still a favorable reaction.
ATP as Energy Currency
• ATP hydrolysis drives many unfavorable
reactions to completion.
• ATP is made in two exergonic processes in the
cell (glycolysis and oxidative phosphorylation)
• The total quantity of ATP in a human body is
about 100 g.
• ATP is not membrane-permeable, and not exchanged among cells. Every cell needs to synthesize all
of their ATP themselves.
• ATP is short-lived (seconds), and must be constantly replenished => no ATP synthesis (through
glycolysis and oxidative phosphorylation) = death
• ATP is turned over at a very high rate: At rest, humans consume about 40 kg of ATP in a day. During
strenuous exercise, this can increase to about 450 g per minute.
ATP acts as a energy currency because quite a lot of endergonic reactions can be linked to ATP
hydrolysis. Some of the processes that require ATP (Ex. signal transduction, membrane transport) are
happening constantly.
The catabolism of nutrients into some waste products coupled with the production of ATP. If you want
to have an anabolic pathway where you have the precursor turning into a product, you are using up ATP,
resulting ADP and Pi. The core of your ATP is not really used up but mostly ATP into ADP that is coupled
with catabolic and anabolic reactions.
• ATP is not the only molecule with a high energy phosphate.
• Several molecules can drive unfavourable reactions.
ATP is the most common of energy molecules, which is used by
lots of enzymes. ATPases uses ATP. ATP can be turned into ADP
and also AMP. The PPi is pyrophosphate and is basically two
phosphate groups together, which can be then hydrolyzed into
two separate phosphates, resulting in more energy release. The
formation of AMP into ATP would require more energy than
the transition from ADP into ATP.
