Intermediary Metabolism:
1.
Understand the concept of a pathway as a cascaded series of enzyme-catalysed
reactions.

Metabolism represents the sum of chemical changes that convert nutrients from
the food we eat into energy and the chemically complex finished products of
cells.
This process consists of hundreds of enzymatic reactions organized into discrete
pathways.
These pathways proceed in a stepwise fashion, transforming substrates into end
products through many specific chemical intermediates.
Each reaction or step of the pathway is catalysed by a specific enzyme
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2.
Be familiar with the common types of reactions including phosphorylation and
redox reactions.
There are 3 principal reaction types:
1. Phosphorylation
The addition of a phosphate group (PO43-) to an organic compound.
Eg: add phosphate to glucose = glucose monophosphate. Or phosphorylation
may, for example, involve the addition of phosphate to ADP [adenosine
diphosphate] to form ATP [adenosine triphosphate].
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Phosphorylation is carried out through the action of enzymes known as
phosphotransferases or kinases.
2. Isomerisation
The rearrangement of atoms within a molecule, forms another compound with
the same molecular formula but different properties. A process in which one
isomer is formed from another.
The process whereby any isomer is converted into another isomer, usually
requiring special conditions of temperature, pressure, or catalysts.
See Reaction. 2 Below.
Reaction 1: Phosphate Ester
Synthesis
Phosphate is added to the glucose at
the C-6 position. The reaction is a
phosphate ester synthesis using the
alcohol on the glucose and a
phosphate from ATP.
This first reaction is endothermic and
thus requires energy from a coupled
reaction with ATP. ATP is used by
being hydrolyzed to ADP and
phosphate giving off energy and the
phosphate for reaction with the
glucose for a net loss of ATP in the
overall glycolysis pathway.
Hydrolysis: ATP + H2O --> ADP + P
+ energy
P = PO4-3; ATP = adenine
triphosphate;ADP = adenine
diphosphate.
This reaction is catalyzed by
hexokinase.
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Reaction 2: Isomerization
The glucose-6-phosphate is changed
into an isomer, fructose-6-phosphate.
This means that the number of atoms
is unchanged, but their positions have
changed.
This works because the ring forms
may open to the chain form, and then
the aldehyde group on glucose is
transformed to the keone group on
fructose. The ring then closes to form
the fructose-6-phosphate.
This reaction is catalyzed by
phosphoglucoisomerase.
Off-site chime link:
Phosphoglucoisomerase
3. Oxidation/reduction:
 Involves a transfer of electrons.

o Oxidation Involves a Loss of electrons. (Gaining charge – often
involving oxygen, therefore name, but doesn’t have to be oxygen)
o OIL
o Reduction Involves a Gain in electrons (charge reduced).
o RIG
(Remember “OIL RIG”)
 Electrons are usually transferred in biological systems in 3 different ways:
-
As hydrogen ions
-
As hydride ions (H-)
-
Through combination with O2
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A good example is the reaction between hydrogen and fluorine in which hydrogen is being
oxidized and fluorine is being reduced:
H2 + F2 → 2 HF
We can write this overall reaction as two half-reactions:
the oxidation reaction:
H2 → 2 H+ + 2 e− (electrons lost)
and the reduction reaction:
F2 + 2 e− → 2 F−
(electrons gained, charge reduced)
Many important biological processes involve redox reactions.
Cellular respiration, for instance, is the oxidation of glucose (C6H12O6) to CO2 and the
reduction of oxygen to water. The summary equation for cell respiration is:
C6H12O6 + 6 O2 → 6 CO2 + 6 H2O
3.
Explain why some reactions are readily reversible, and some essentially
irreversible, in terms of delta G of the reaction.
The fundamental concept is that all reactions in the metabolic pathway are reversible
(substrate – product –substrate) or irreversible (substrate – product). However, to
understand this concept more fully a few definitions and laws need to be realized.
Firstly, it must be noted that all reactions will spontaneously react in a manner that
drives them towards their equilibrium position. The equilibrium position can be
described as the point in which the forward and reverse reactions are occurring at
the same rate or where its change in free energy (∆G) is closest to zero. Now free
energy (G) is basically the amount of energy that is capable of doing work during a
reaction. In irreversible reactions, the free energy change is large and negative (ie
energy is released). In comparison, in reversible reactions, the free energy change
is approximately zero (ie little change in energy). This means that if the reactants
and products have relatively the same free energy then their respective
concentration will stay the same unless acted on by external sources (ie change in
temp - which doesn’t often normally happen in the body). Alternatively, if the free
energy level of the products is less then that of the reactants, then the reaction will
occur in that direction. This is the main concept relating to many of the metabolic
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pathways and enzymatic reactions which have such a large difference in free energy
that the reactions can be considered irreversible.
What is also needed now are the two fundamental laws of thermodynamics. These
are:
1 - Energy is always conserved (ie energy can change from one form to the
other but can never be created or destroyed).
2 - In all natural processes the entropy of the universe will increase (ie the
universe always tends towards increasing disorder).
Now, entropy (S) is simply a quantitative measure of the randomness or disorder of
a system. For example, water is more disordered then ice, and therefore will have
greater entropy. Furthermore, enthalpy (H) is the heat content of a reacting system.
If the system loses heat, the reaction is said to be exothermic, whereas if the system
uses heat it is said to be endothermic. Generally, all metabolic reactions in the body
are carried out in the exothermic direction (ie body will lose energy as heat). This is
an important concept to note as it means that a lot of potential energy that is
produced by the metabolism of nutrients is not converted to useable energy, but
rather wasted.
Due to the fact that organisms like to keep a stable and ordered environment, this
seems to contradict the second law of thermodynamics. However, living organisms
preserve their internal order by taking free energy from their surroundings in the form
of nutrients, and returning to their surroundings an equal amount of energy in the
form of heat and entropy.
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4.
Explain, in outline only, how energy derived from the oxidation of food molecules
is used to generate energy in the form of ATP.
Firstly, metabolism is the process whereby food molecules are broken down to
provide energy and building blocks. The energy is ‘made’ in basic terms by two
steps; the oxidation of these food molecules; and the synthesis of ATP which is the
most common form of energy within the body. An oxidation reaction is simply one in
which electrons are lost. The creation of ATP can be divided into three separate
processes.

The first step involved in obtaining energy from food molecules is the conversion
of amino acids, fatty acids, and glucose into acetyl CoA. The process of
glycolysis alone which converts glucose into pyruvate and then acetyl CoA will
produce two ATP molecules itself.

The second step is known as the citric acid cycle, or KREBS cycle, or
tricarboxylic acid (TCA) cycle, which begins with acetyl CoA and involves a
number of redox reactions that produce 2 more molecules of ATP and various
molecules of NADH and FADH2 as ‘by-products’.

The final step involves the electron transport chain together with oxidative
phosphorylation which are driven by the energy derived from reoxidized NADH
and FADH2. This final step occurs along the mitochondrial membrane and
involves a flow of electrons that results in a H+ gradient across the membrane.
This H+ gradient drives the synthesis of ATP from ADP & Pi. This results in the
formation of about 34 ATP molecules (from one molecule of Acetyl CoA).
Therefore, when combining the three steps in the metabolism of carbohydrate,
approximately 38 ATP molecules are formed/molecule of glucose. These ATP
molecules can then be broken down to ADP and Pi creating a large amount of
energy that body cells can use to drive their functions.
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