CH3104

Biochemical Engineering

Asst Prof TAN Meng How

N1.2-B2-33
mh.tan@ntu.edu.sg

1
Lecture 3 Metabolism

2
Why do biochemical engineers care
about cellular metabolism?
Goal: To select an organism to efficiently make a given product at high yield for a
sustained period of time

With the development of genetic engineering tools, we can remove or add genes
to an organism

The engineer must understand the metabolic capabilities of the cell either to use
them directly or to know how to redirect metabolic pathways to make the desired
product

One of the biggest challenges in the engineering of cells for the production of
high value compounds is balancing the metabolic flux:
- Metabolic networks are strongly influenced by a few key central metabolites
- Multiple pathways are regulated by these metabolites
- Introduction of heterologous (foreign) genes or pathways into the cells can
perturb the levels of these metabolites, often in unexpected ways
 Some terms
Catabolism is the intracellular process of degrading
a compound into smaller and simpler products (e.g.
glucose to CO2 and H2O). Catabolism produces
energy for the cell.

Anabolism is the synthesis of more complex

compounds in living organisms from simpler
molecules (e.g. glucose to glycogen) and requires
energy.
 Types of metabolic reactions
Metabolic networks appear to be complex and can vary from
organism to organism

However, the reactions can be broadly classified:

- Degradation of nutrients
- Biosynthesis of small molecules (amino acids, nucleotides etc)
- Biosynthesis of large molecules

These reactions take place in the cell simultaneously to form

different end products, which can be valuable for human and
animal consumption
 Coupling of reactions
A thermodynamically unfavorable reaction can
be driven by a favorable reaction when the two
reactions are coupled.

Example:

- The conversion of A into C and D can occur spontaneously

- The intermediate B, common to both reactions, couples the reactions
 ATP: the cells energy currency
Cell metabolism is facilitated by adenosine
triphosphate (ATP)
Part of the free energy derived from the
oxidation of foodstuffs and from light is
transformed into ATP
ATP is an energy-rich molecule because
of its phosphoanhydride bonds
 Energy release
A large amount of free energy is liberated
when ATP is hydrolyzed:

ADP can also be hydrolyzed to release

energy:
 Coupling ATP hydrolysis to
biosynthetic reactions
Consider a chemical reaction that is thermodynamically
unfavorable (common in the cell):

The equilibrium constant and the free energy change are

related:

So, the equilibrium constant of this reaction at 25oC is

related to the free energy change (in kcal per mol) by:

Thus, net conversion of A into B cannot occur when the

molar ratio of B to A is greater than 1.15 x 10 -3!
 Coupling ATP hydrolysis to
biosynthetic reactions
Now consider what happens when the reaction is coupled
to ATP hydrolysis:

The new equilibrium constant is:

The cell always maintains a very high ratio of [ATP] to

[ADP][Pi], typically around 500 M-1. Hence, the molar ratio
of B to A is:

Hence, by coupling ATP hydrolysis with the conversion of A into

B, the equilibrium constant has changed by a factor of 10 8!
 Phosphoryl transfer potential
ATP is not the only compound in the cell that can store and
transfer high energy phosphate bonds.
In fact, some compounds in biological systems have a higher
phosphoryl transfer potential than that of ATP and include
phosphoenolpyruvate (PEP) and creatine phosphate.
Thus, PEP can transfer its phosphoryl group to ADP to form
ATP. Energy stored in ATP is later transferred to lower energy
phosphate compounds such as glucose 6-phosphate.

Creatine phosphate in muscle

serves as a reservoir of high-
potential phosphoryl groups
It is the major source of phosphoryl
groups for ATP regeneration for a
runner during the first few seconds of
a sprint
 Oxidation of carbon fuels
Turnover of ATP is very high:
- In a cell, an ATP molecule is consumed within a minute of
its formation.
- A resting human consumes about 40kg of ATP in a day.
It is important to have mechanisms for regenerating ATP.
The carbon in fuel molecules, such as glucose and fat, is
oxidized to CO2 and the energy released is used to
regenerate ATP from ADP and Pi.
The more reduced a carbon is to begin with, the more
energy will be released during its oxidation.
 Activated carriers - ATP
Activated carriers are molecules that can be split to release
free energy

ATP is an activated carrier of phosphoryl groups because

phosphoryl transfer from ATP releases free energy.

What other activated carriers are there in the cell?

 Activated carriers NAD+
In aerobic organisms, the ultimate electron acceptor is O2. However,
electrons are not transferred directly to O2. Instead, fuel molecules
transfer electrons to special carriers, which are either pyridine
nucleotides or flavins. These carriers then transfer their electrons to O 2.

Nicotinamide adenine dinucleotide is a major electron

carrier in the oxidation of fuel molecules.
The oxidized and reduced forms are abbreviated as NAD+
and NADH respectively.
NAD+ is the electron acceptor in many reactions of the type:

During oxidation of a substrate, NAD+ accepts a hydrogen

ion and two electrons.
 Activated carriers - FAD
Flavin adenine dinucleotide is
the other major electron carrier in
the oxidation of fuel molecules.
The oxidized and reduced forms
are abbreviated as FAD and
FADH2 respectively.
FAD is the electron acceptor in
many reactions of the type:

The structure of FAD consists

During oxidation of a substrate,
FAD takes up two protons and also
accept two electrons.
of a flavin mononucleotide
(FMN) unit (shown in blue) and
an AMP unit (shown in black)
 Activated carriers NADP +

In most biosynthetic reactions, the precursors are more

oxidized than the products.
Hence, reducing power is needed.
For example, in the biosynthesis of fatty acids, a keto
group is reduced to a methylene group:

The electron donor in most reductive biosyntheses is

NADPH, the reduced form of nicotinamide adenine
dinucleotide phosphate (NADP+).
Difference between NAD+ and NADP+
NADP+ differs from NAD+ in that the 2-hydroxyl group of
its adenosine moiety is esterified with phosphate.

In NAD+, R = H;
In NADP+, R = PO32-

Although NADPH carries electrons in the same way as

NADH, NADPH is used almost exclusively for reductive
biosyntheses, whereas NADH is used primarily for the
generation of ATP.
 Activated carriers - CoA
Coenzyme A (CoA), a central molecule in metabolism, is a carrier of acyl groups.
The terminal sulfhydryl group in CoA is the reactive site.

Acyl groups are linked to CoA by thioester bonds.

An acyl group often linked to CoA is the acetyl unit.

Hydrolysis of acetyl CoA releases a large amount of energy:

Acetyl CoA carries an activated acetyl group, just as ATP carries an activated
phosphoryl group.
 Use of activated carriers illustrate
two key aspects of metabolism
In the absence of catalysts, NADH, NADPH, and FADH2 react
slowly with O2, while ATP and acetyl CoA are hydrolyzed
slowly. The kinetic stability of these molecules in the absence
of catalysts is essential for their biological function because it
enables enzymes to control the flow of free energy and
reducing power.

Most interchanges of activated groups in metabolism are

accomplished by a small set of carriers. This is true in all
living organisms a small set of molecules carries out a very
wide range of tasks.
 Food for thought

20
What happens to the chocolate bar after you eat it?
Stages in the Extraction of Energy from Food
Stage I: Large molecules in food are broken down into their
constituents. This stage is strictly preparatory as no useful
energy is captured.
Stage II: The food constituents are
degraded to a few simple molecules
that play central roles in metabolism.
One of these molecules is acetyl CoA.
A little ATP is generated in this stage.

Stage III: ATP is produced from the

complete oxidation of the acetyl unit
of acetyl CoA. The key processes in
this stage include the citric acid cycle
and oxidative phosphorylation, which
generate a lot of ATP.
 What is glycolysis?
Glycolysis, or the Embden-Meyerhof-
Parnas (EMP) pathway, is the sequence
of reactions that metabolizes one
molecule of glucose to two molecules of
pyruvate with the concomitant net
production of two molecules of ATP.
This process does not require oxygen.
Pyruvate can be further processed
- anaerobically (fermented) to lactate
(lactic acid fermentation) or ethanol
(alcoholic fermentation)
- aerobically to CO2, generating much
more ATP than fermentation
Stages of glycolysis

Stage 1: Glucose is trapped and

destabilized

Stage 2: Two interconvertible three-carbon

molecules are generated by cleavage of six-
carbon fructose

Stage 3: ATP is generated

Phosphofructokinase is highly regulated
Metabolic pathways are often tightly regulated in
different ways.

In glycolysis, phosphofructokinase is the most

important control element

High levels of ATP allosterically inhibit the enzyme in

the liver, thus lowering its affinity for fructose 6-
phosphate

Phosphofructokinase is also inhibited by citrate, an

early intermediate in the citric acid cycle

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 Summary of glycolysis
The net reaction in the transformation of glucose to pyruvate:
 Biochemical hub of the cell

Traffic roundabouts function as hubs to facilitate traffic flow.

The citric acid cycle is the biochemical hub of the cell,
oxidizing carbon fuels, usually in the form of acetyl CoA, as
well as serving as a source of precursors for biosynthesis.
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 What is the citric acid cycle?
The citric acid cycle is a series of enzyme-catalyzed chemical reactions
that form a key part of aerobic respiration in cells. This cycle is also called
the Krebs cycle or the tricarboxylic acid cycle (TCA cycle).

From glycolysis, glucose is metabolized to pyruvate to synthesize

ATP.

However, glycolysis harvests only a small fraction of ATP available

from glucose.

Aerobic processing of glucose, which generates a lot more ATP,

begins with the complete oxidation of glucose derivatives to CO 2 in
the TCA cycle.

The reactions of TCA take place inside mitochondria, in contrast

with those of glycolysis, which take place in the cytosol.
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 Overview of the citric acid cycle
Oxaloacetate (four-carbon compound) condenses with a two-carbon acetyl unit
to form citrate (six-carbon)
An isomer of citrate is decarboxylated to form -ketoglutarate (a five-carbon
compound)
-ketoglutarate is decarboxylated to form succinate (a four-carbon compound)
Oxaloacetate is then regenerated from succinate

Two carbon atoms enter the cycle as an acetyl unit

Acetyl CoA Two carbon atoms leave the cycle in the form of two
molecules of CO2
The function of the cycle is the harvesting of
electrons from carbon fuels:
- Six electrons are transferred to NAD+
- Two electrons are transferred to FAD
The cycle itself does not generate ATP nor require O2
However, NADH and FADH2 are used in an
immediate downstream process called oxidative
phosphorylation to generate a lot of ATP
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 Where does acetyl CoA come from?
Recall that pyruvate is produced by glycolysis in the cytosol
The pyruvate is actively transported into the mitochondria
In the mitochondrial matrix, pyruvate is oxidatively decarboxylated by
the pyruvate dehydrogenase complex to form acetyl CoA:

This irreversible reaction is the link between glycolysis and the citric
acid cycle
Acetyl CoA is also formed from the breakdown of glycogen (the storage
29
form of glucose), fats, and many amino acids
 More details of the TCA cycle
The net reaction of the TCA cycle is:

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Feedback inhibition in the Krebs cycle
Metabolic pathways are often regulated in
different ways.

In the Krebs cycle, the activities of several

enzymes are regulated by feedback inhibition.

Pyruvate dehydrogenase is inhibited by ATP,

NADH, and acetyl CoA, but activated by ADP,
AMP, and NAD+.

Citrate synthase is inhibited by ATP but

activated by ADP and AMP

In general, high ATP/ADP and NADH/NAD+

ratios reduce the processing rate of the TCA
cycle.
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 The TCA cycle is a source
of biosynthetic precursors
As a major metabolic hub of the cell, the TCA cycle also
provides intermediates or carbon skeletons for biosyntheses.

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Overview of oxidative phosphorylation
The NADH and FADH2 formed in glycolysis and the TCA
cycle (and also fatty acid oxidation) are energy-rich
molecules.

When these electrons are used to reduce O2 to H2O, a

large amount of free energy is liberated, which can be
used to generate ATP.

Oxidative phosphorylation is the process in which ATP is

formed as a result of the transfer of electrons from NADH
or FADH2 to O2 by a series of electron carriers.

This process takes place in the mitochondria. 33

Generation of a proton-motive force
Electrons are not transferred directly from NADH/ FADH2 to O2
Instead, electrons are moved through a series of protein
complexes located in the mitochondrial inner membrane
As the electrons are transported, protons are pumped out of
the mitochondrial matrix
The uneven distribution of protons generates a pH gradient
and a transmembrane electrical potential
When protons flow back to the mitochondrial matrix through an
enzyme complex, ATP is synthesized

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Movement of electrons through complexes
Complex I: NADH-Q oxidoreductase
Complex II: Succinate-Q reductase
Complex III: Q-cytochrome C oxidoreductase
Complex IV: Cytochrome c oxidase

Electrons are transferred from NADH to

complex I and then to a highly mobile
hydrophobic carrier called ubiquinone (QH2).

The citric acid cycle enzyme succinate

dehydrogenase is a component of complex II,
which donates electrons from FADH2 to QH2.

Electrons are transferred from QH2 to complex

III, then to cytochrome c (another mobile
carrier), and then to complex IV.

Finally, complex IV transfers the electrons to

O2, the ultimate acceptor, to form H2O.

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Complexes I, III, and IV pumps protons out of
Worlds smallest molecular motor!

Matrix

Inner Membrane

Intermembrane
Space
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ATP Synthase
 Part of the ATP synthase rotates
Intermembrane Each proton enters the cytosolic half-channel, follows a
Space complete rotation of the c ring, and then exits through
the other half-channel into the matrix.
The proton flow around the c ring powers ATP synthesis
The subunit rotates and causes the three subunits to
continually change conformations.
- In the O (open) confirmation, ADP and Pi enter.
- In the L confirmation, the bound ADP and Pi are trapped
and cannot escape.
- In the T (tight) confirmation, ADP and Pi can be
Matrix converted into ATP.
- In the O confirmation again, the ATP is released, before
new ADP and Pi enter for a new cycle.

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Video of ATP synthase

ATP synthase in motion

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ATP yield from the complete oxidation of glucose

1 molecule of glucose 30 molecules of ATP 39

 Gluconeogenesis
So far, we have looked at the breakdown of
glucose. What if we need more glucose?
Typical adult brain consumes about 120g of
glucose everyday. Red blood cells can use only
glucose as fuel.
Gluconeogenesis is the biosynthesis of new
glucose in the cell (endogenous glucose
production).
The major site of gluconeogenesis is the liver, with
a small amount also taking place in the kidney.
Gluconeogenesis is not a reversal of glycolysis!
Glycolysis: glucose pyruvate
Gluconeogenesis: pyruvate glucose
G for glycolysis is -20 kcal mol-1 (-84 kJ mol-1).
Most of the decrease in free energy comes from
three essentially irreversible steps:
 Different steps in gluconeogenesis
In gluconeogenesis, the following new steps replace the three
virtually irreversible reactions of glycolysis:
1) Phosphoenolpyruvate (PEP) is formed from pyrvuate via an intermediate:

2) Fructose 6-phosphate is formed from fructose 1,6-bisphosphate by hydrolysis.

The enzyme fructose 1,6-bisphosphatase catalyzes this exergonic reaction:

3) Glucose is formed from glucose 6-phosphate by hydrolysis, which is

catalyzed by the enzyme glucose 6-phosphatase:
 The cost of gluconeogenesis
If gluconeogenesis is simply a reversal of glycolysis, the overall
reaction would be:

The actual stoichiometry of gluconeogenesis is:

Note that six nucleotide triphosphate molecules are hydrolyzed to

synthesize glucose from pyruvate. However, only two molecules of ATP
are generated in glycolysis.

Thus, the extra cost of gluconeogenesis is four high phosphoryl

transfer potential molecules per molecule of glucose synthesized, in
order to turn an energetically unfavorable process into a favorable one.
Regulation of gluconeogenesis & glycolysis

Gluconeogenesis and
glycolysis are coordinated, so
that only one pathway is active,
while the other is inactive.

When energy charge is high

and biosynthetic intermediates
are abundant, glycolysis is
switched off and
gluconeogenesis is promoted.
 What is photosynthesis?
Photosynthesis is a chemical process through which plants and certain
species of bacteria and algae can produce glucose and oxygen from
carbon dioxide and water, using only light as an energy source.

Photosynthesis is the source of essentially

all the carbon compounds and all the
oxygen that makes aerobic metabolism
possible

More than 1017 kcal (4.2 x 1017 kJ) of free

energy is stored annually by photosynthesis,
which corresponds to the assimiliation of
more than 1010 tons of carbon into
carbohydrate and other organic matter
Photosynthesis is divided into two parts
The basic equation of photosynthesis is deceptively simple! The mechanism of
photosynthesis is complex and requires many proteins and small molecules.

Photosynthesis can be divided into:

(1) light reactions
(2) dark reactions

Light reactions need light to produce

energy molecules (ATP and NADPH). They
are initiated by colored pigments, mainly
green colored chlorophylls.

Dark reactions make use of the energy

molecules (ATP and NADPH). This reaction
cycle is also called Calvin Benison Cycle.
ATP provides the energy, while NADPH
provides the electrons required to fix CO2
into carbohydrates.
Photosynthesis takes place in chloroplasts

The conversion of light into chemical energy takes place in a

compartment known as the chloroplast.
Within the chloroplast are membranous structures called thylakoids,
which are flattened sacs or discs.
Thus, chloroplasts have three different membranes (outer, inner, and
thylakoid membranes) and three different spaces (intermembrane,
stroma, and thylakoid spaces).
Light reactions take place in the thylakoid.
Dark reactions take place in the stroma.
 Absorption of light energy by chlorophyll
The first event in photosynthesis is the absorption of light by a photoreceptor.
The main photoreceptor in the chloroplasts of green plants is chlorophyll a.
The energy from light excites an electron from its ground energy level to an excited
energy level.
This high-energy electron can have two fates:
(1) The electron simply returns back to the ground state and the absorbed energy is
converted to heat.
(2) If an electron acceptor is nearby, the excited electron can move from the initial
molecule to the acceptor.
- The second process results in the formation of a positive charge on the initial
molecule and a negative charge on the acceptor and is referred to as photoinduced
charge separation.
- The site where the separational change occurs is called the reaction center.
Help from accessory pigments
A light-harvesting system that relies only on chlorophyll a would be
inefficient:
(1) Chlorophyll a molecules absorb light only at specific wavelengths
(2) Even in spectral regions where chlorophyll a absorbs light, many
photons would still be wasted due to the low density of
chlorophyll a molecules in a reaction center.

Accessory pigments (other types of chlorophylls and other classes of

molecules) also help to absorb light and funnel the energy to the
reaction center through a process known as resonance energy
transfer, where energy absorbed by one molecule can be transferred
to nearby molecules with excited states of equal or lower energy.
 Transfer of electrons in the chloroplast
Photosystem II Cytochrome bf Photosystem I
(P680) (no light absorption) (P700)

Electrons are moved between different protein complexes in

the thylakoid membrane
Photosystem II: Excitation of P680, a special pair of
chlorophyll a molecules, leads to electron transfer to an
activated carrier called plastoquinone (Q). The electrons are
replenished by the extraction of electrons from water in the
thylakoid lumen to generate O2.
The plastoquinol (QH2) produced at photosystem II is
reoxidized by the cytochrome bf complex, which transfers the
electrons to plastocyanin. The protons from the oxidation of
QH2 are released into the thylakoid lumen.
Photosystem I: Excitation of P700, another special pair of
chlorophyll a molecules, releases electrons that are used to
reduce NADP+ to NADPH. The electrons are replenished by
the plastocyanin from the cytochrome bf complex.
A proton gradient builds up across the thylakoid membrane.
Comparison of light reactions
and oxidative phosphorylation
Photosynthesis: Light-induced electron transfer
drives protons into the thylakoid lumen. The
excess protons flow out of the lumen through
ATP synthase to generate ATP in the stroma

Oxidative phosphorylation: Electron flow

down the electron transport chain pumps
protons out of the mitochondrial matrix. Excess
protons then flow back into the matrix through
ATP synthase to generate ATP in the matrix.

The ATP synthase of chloroplasts closely

resemble that of mitochondria.
- The subunits of corn chloroplast ATP
synthase are more than 60% identical in amino
acid sequence with those of human ATP
synthase, although the plant and animal lineages
have separated for about a billion years!
 Demonstration that a proton
gradient drives ATP synthesis
In 1966, Andr Jagendorf showed that chloroplasts
synthesize ATP in the dark when an artificial pH gradient
is imposed across the thylakoid membrane.

To create this transient pH gradient, he soaked

chloroplasts in a pH 4 buffer for several hours.

He then rapidly mixed them with a pH 8 buffer

containing ADP and Pi. Hence, the pH of the stroma
suddenly increased to 8, whereas the pH of the
thylakoid space remained at 4.

A burst of ATP synthesis then accompanied the

disappearance of the pH gradient across the thylakoid
membrane.

This also demonstrates that the purpose of the light in

photosynthesis is to generate the requisite pH gradient.
Similarity between photosynthetic
bacteria and plants
Photosynthetic bacteria are a unique species of microorganisms that use the sun
as a source of energy.

Plants use chlorophyll to absorb light energy. Some bacteria contain a similar
compound called bacteriochlorophyll, which allows them to also photosynthesize.

Photosynthesis in green plants is mediated by two kinds of membrane-bound,

light-sensitive complexes, photosystem I and photosystem II. Photosynthetic
bacteria contain a simpler, single type of reaction center. However, the results of
sequence comparisons and structural studies indicate that the bacterial reaction
center is homologous to the more complex plant systems and work in a similar way
to the plant photosystems I and II.

Cyanobacteria, a species of photosynthetic bacteria

 The dark reactions
So far, we have learnt about the light reactions, which transform light energy into
ATP and NADPH.

Recall that NADH and NADPH differ at a single side chain in the adenosine moiety.
NADH is oxidized by the respiratory chain to generate ATP, whereas NADPH serves
as a reductant in biosynthetic processes.

In NAD+, R = H;
In NADP+, R = PO32-

Photosynthesis proceeds in two parts: the light reactions and the dark reactions,
which constitute the Calvin cycle.

The dark reactions do not depend directly on the presence of light.

 Overview of the Calvin cycle
The Calvin cycle comprises three stages:
Stage 1 (carbon fixation) - CO2 is incorporated into a five-carbon sugar named
ribulose 1,5-bisphosphate (RuBP). The enzyme that catalyzes this first step is
RuBP carboxylase or rubisco. It is the most abundant protein in chloroplasts and
probably the most abundant protein on Earth. The product of the reaction is an
unstable six-carbon intermediate, which splits immediately to form two molecules
of 3-phosphoglycerate.
Stage 2 (reduction) - ATP and NADPH from the light reactions are used to
convert 3-phosphoglycerate to glyceraldehyde 3-phosphate, the three-carbon
carbohydrate precursor to glucose and other sugars.
Stage 3 (regeneration) - more ATP is used to convert some of the
glyceraldehyde 3-phosphate back to RuBP, thereby completing the cycle.

The light reactions sustain the

Calvin cycle by regenerating
the ATP and NADPH.

(enters gluconeogenesis pathway)

Comparison with glycolysis

Some steps in the Calvin cycle are essentially the

reversal of reactions in the glycolytic pathway.

For example:
3-phosphoglycerate glyceraldehyde 3-phosphate
*
-The same 1,3-bisphosphoglycerate intermediate is
generated with the consumption of ATP.
- The enzyme glyceraldehyde 3-phosphate
dehydrogenase in chloroplasts is specific for
NADPH rather than NADH. *
More details on the Calvin cycle

(enters gluconeogenesis pathway)

 Regulation of the Calvin cycle
The rate-limiting step in the Calvin cycle is the carboxylation of ribulose 1,5-bisphosphate
to form two molecules of 3-phosphoglycerate.

The enzyme rubisco is more active at an alkaline pH and a high Mg 2+ ion concentration.

Recall that in the presence of light, there is a net influx of protons into the thylakoid
space. This causes the pH in the stroma to increase.

In addition, the concentration of magnesium rises in the stroma because Mg 2+ ions from
the thylakoid space are released into the stroma to compensate for the influx of protons.

Hence, the activity of rubisco increases markedly on illumination!

The concentration changes of protons and magnesium help to couple the Calvin cycle to
the light reactions.
 Requirements for NADPH
NADPH is widely used in all living organisms for (1) reductive biosynthesis
and (2) protection against the toxicity of reactive oxygen species.

The major source of NADPH in animals and other non-photosynthetic

organisms is the pentose phosphate pathway. It provides a means by which
glucose can be oxidized to generate NADPH.

Like glycolysis and gluconeogenesis, the Calvin cycle and the pentose
phosphate pathway can be simply thought of as being mirror images of each
other. The Calvin cycle uses NADPH to reduce CO2 to generate hexoses,
whereas the pentose phosphate pathway breaks down glucose into CO2 to
generate NADPH.
The pentose phosphate pathway
This pathway occurs in the cytosol and
consists of two phases:
- An oxidative phase
- A non-oxidative phase

In the oxidative phase, NADPH is generated

when glucose 6-phosphate is oxidized to ribose
5-phosphate. This five-carbon sugar and its
derivatives are components of DNA and RNA
as well as ATP, NADH, FAD, and CoA.

In the non-oxidative phase, the pathway

catalyzes the interconversion of three-, four-,
five-, six-, and seven-carbon sugars. The
various carbon skeletons are important
precursors for the synthesis of cellular
compounds. For example, erythose 4-
phosphate can be used to synthesize aromatic
amino acids.
 Summary of metabolism
Activated carriers - ATP
- NAD+
- FAD
- NADP+
- CoA

Metabolic pathways - Glycolysis

- The TCA cycle
- Oxidative phosphorylation
- Gluconeogenesis
- Light reactions of photosynthesis
- Calvin cycle
- The pentose phosphate pathway