Introduction to Metabolism

Lecture Outcomes
● Understand the role of ATP in providing the energy required to do
work in the cell
● Appreciate how the energy from ATP is used to do work
● Understand the role of enzymes in speeding up metabolic reactions,
including their function, and what factors affect their function
Endergonic and Exergonic Reactions
● Metabolic reactions that release free energy = Exergonic
● Metabolic reactions that absorb free energy = Endergonic
● Reactions in an isolated system will eventually reach equilibrium
● At equilibrium, the cell has minimum free energy
● Without energy to do work, a cell would be dead
● Cells avoid reaching an equilibrium, because they are an open
system
● The constant flow of molecules in and out of the cell ensures that the
cell never reaches equilibrium
A Cell Does Three Main Types of Work
Chemical work Mechanical work Transport work
Three Types of Work
● Chemical work = pushing endergonic reactions that would not occur
spontaneously e.g. synthesis of polymers from monomers
● Transport work = pumping substances across membranes against
their concentration gradient
● Mechanical work = (remember we saw in Chapter 4 that cytoskeleton
can act as a transport system?) other examples: beating of cilia, the
contraction of muscle cells, and the movement of chromosomes
during cellular reproduction
Where Does this Energy Come From?
● Energy to do work comes from exergonic reactions
● The cell needs a way of transferring energy from an exergonic
process (e.g. break down of sugar in respiration) to an endergonic
process (e.g. Na+/K+ pump)
● This transfer of energy relies on a molecule called ATP
ATP: Adenosine Triphosphate
● ATP is made by adding a third phosphate to ADP (adenosine
diphosphate, which has two phosphates). This is a dehydration
reaction so water is also released

+ H2O

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● The products of the reaction ATP and H2O have more free energy
than the reactants ADP and phosphate (shortened to Pi)
● Energy released from exergonic reactions is used to make ATP and
water
● This energy is now stored as free energy in ATP and H2O
● When energy is needed, ATP can be broken down by hydrolysis
(adding water) to give back ADP and Pi
● In this reaction, the two products ADP and Pi have less free energy
than the reactants ATP and water
● That means that some free energy was released out
How Does the Cell Use Energy from ATP to Do
Work?
1. The Energy Itself is Released as Heat
● If we performed ATP hydrolysis in a test tube in the lab, it will release
energy in the form of heat
● In the cell, using ATP to generate heat could be useful sometimes
● However, this is not always the best way to use ATP
2. Phosphorylated Intermediates
● If ΔG of an endergonic reaction is less than the amount of energy
released by ATP, then the two reaction can be combined and still
have a negative ΔG
● Combining two reactions = coupling
● So an endergonic reaction with a positive ΔG of smaller number than
the negative ΔG of ATP hydrolysis can be coupled to ATP hydrolysis
and still have negative ΔG overall
● For example, the ΔG of the reaction above is +3.4 kcal/mol
● The ΔG of ATP hydrolysis is -7.3 kcal/mol
● +3.4 added to -7.3 = -3.9 kcal/mol
● Combining the two ΔG values still gave us a negative ΔG
● This means the cell can couple the two reactions
This is useful because the reaction of glutamic acid + ammonia would never
have happened spontaneously because it had a positive ΔG value
But now that we coupled it with ATP reaction, the total ΔG value is negative
So the experiment can now take place
Coupling Endergonic Reactions with ATP Hydrolysis
● So how do two reactions get coupled together?
● This happens by adding in a step in the middle
● ATP transfers its phosphate to glutamic acid
● And then ammonia replaces the phosphate molecule
● This middle step, where phosphate was added, is known as
phosphorylation
● The phosphorylated glutamic acid is referred to as phosphorylated
intermediate (in this case intermediate molecule is a temporary
molecule formed in-between the two steps of the reaction)
● The phosphorylated intermediate is less stable than the original
molecule. This will make the reaction more spontaneous as the
system tries to move towards a more stable state
3. Changing the Protein’s Shape
● ATP can provide its phosphate group to a protein
● The phosphate group will change the shape of the protein, which will
allow it to perform a particular function (=job)
● Afterwards, the phosphate group is removed and the protein changes
shape again
● This way, the protein can switch between two shapes, depending on
whether phosphate is added or not
● An e.g. of this is the Na+/K+ ion pump in the next slide
Example
● Na+/K+ pump is open to the inside of the cell, where Na+ can bind
● Then phosphate from ATP is attached to it
● The attachment of phosphate makes it open to the outside of the cell
and release Na+
● Outside, K+ can now bind to the protein
● Phosphate is now removed from the protein
● The protein goes back to its original shape, opening to the inside of
the cell and allowing K+ to enter
● Non-covalent bonding by ATP also changes the shape of motor
proteins, allowing them to “walk” along the cytoskeleton
What About the Rate of Reaction?
Rate of a Reaction
● Studying the thermodynamics of reactions can tell us which reactions
are possible, and which ones need energy to happen
● They do not tell us how fast the reaction will happen
● There’s no point if the reaction is spontaneous but happens at a slow
rate
● The cell needs a way to regulate how fast or how slow reactions
happen
● Speeding up a reaction can be achieved by using enzymes
Enzymes
● Enzymes are like chemical catalysts, but used in living beings
● They can speed up a chemical reaction without being used up by the
reaction
● They do this by lowering the activation energy barrier
Activation Energy Barrier
● For a chemical reaction to
take place, the reactant first
has to transition (=move) to
an unstable state, so that
the bonds can break
● Then new bonds can be
formed
● The first part of a chemical
reaction requires some
energy to make the
molecules unstable enough
to break their bonds
● This is true for all reactions,
whether they are exergonic
or endergonic
● This initial energy requirement
is called energy of activation
(EA)
● In some reactions, the energy
required is so little that the
reaction happens very quickly
● Reactions with a high energy
of activation will happen very
slowly
Enzymes Lower the EA Barrier

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Enzyme Specificity
● During a metabolic reaction, the enzyme binds to the reactant in order
to speed up the reaction
● The reactant that binds to an enzyme is known as a substrate
● The substrate binds to an enzyme at a place called the active site
● Based on their 3d shape, an enzyme can only bind to a specific
substrate. For example, the enzyme sucrase only binds sucrose. It
does not bind maltose. It does not bind any other molecule
Induced Fit Theory
● Substrates bind to an enzyme and are hold onto the active site through
weak interactions
● The enzyme also changes its shape around the substrate
● This forms the enzyme-substrate complex
● The enzyme-substrate complex forces the reactants into the unstable
state required for bonds to break
● New bonds are formed. The products have a different shape than the
reactants, so the enzyme releases them
● Enzyme is back to its original shape and can now accept new reactants
Factors Affecting Enzyme Function
1. Temperature
2. pH
3. Cofactors
4. Inhibitors
Effect of Temperature on Enzyme Activity
● The rate of an enzymatic reaction increases
with increasing temperature, partly because
substrates collide with active sites more
frequently (=substrates have more kinetic
energy, so they bump into the enzyme more
frequently)
● This is increases up to a point, where enzyme
activity is highest. This is called the optimum
temperature
● After that, the enzyme starts to denature, and
becomes less effective
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Effect of pH on Enzyme Activity
● See Chapter 3
● Enzymes have an optimum pH at which they are most effective
● For humans, most enzymes have an optimum pH between 6-8,
except for the stomach
● For humans the optimum temperature for proteins is between 35-
40°C
Cofactors
● Many enzymes require helpers called cofactors
● Cofactors bind to the enzyme and are usually inorganic ions like iron
and calcium ions
● If the cofactors is an organic molecule, it is called a co-enzyme
Inhibitors
● Certain molecules can inhibit enzymes
● Inhibitors can be irreversible or reversible
● Competitive inhibitors : some reversible
inhibitors look like the normal substrate
molecule and compete for admission into
the active site
○ These mimics reduce the productivity
of enzymes by blocking substrates
from entering active sites
Allosteric Binding to Enzymes
● What if a molecule can bind to the enzyme in another place outside
the active site?
● This is known as allosteric binding, and can result in promotion or
inhibition of enzyme activity
Metabolic Regulation
● Cells can regulate the metabolic reactions (=speed up, or slow down) by
regulating the activity of enzymes, usually by allosteric activators and
inhibitors
● Remember we covered positive and negative feedback in Chapter 1?
● If an enzyme is too active and creates too many products, the products at
the end of the reaction can inhibit the enzyme and slow down the reaction
● If the amount of product becomes too little, it cannot inhibit the enzyme
and the enzyme is active once again to speed up the reaction