Metabolism is the sum of all chemical reactions within an organism. Metabolic pathways consist of enzyme-catalyzed reactions organized into linear chains or cyclic pathways. Enzymes lower the activation energy of reactions by binding to substrates and altering their structure. Enzyme inhibitors can competitively or non-competitively bind to enzymes and reduce their activity. Metabolic pathways are regulated by end-product inhibition, which stops pathways once their product reaches a certain concentration. Databases can be used to screen chemicals and identify potential new drugs, like anti-malarial treatments. Rates of enzymatic reactions can be calculated from experimental data and plotted on graphs to determine inhibition type.

1. 8.1 Metabolism (AHL)
Essential idea: Metabolic reactions are regulated in response to the
cell’s needs.
https://mediaeatout.files.wordpress.com/2013/11/candidates-eating-obama-sized.jpg

2. Understandings, Applications and Skills
Statement Guidance
8.1 U.1 Metabolic pathways consist of chains and
cycles of enzyme-catalysed reactions.
8.1 U.2 Enzymes lower the activation energy of the
chemical reactions that they catalyse.
8.1 U.3 Enzyme inhibitors can be competitive or
non-competitive.
Enzyme inhibition should be studied
using one specific example for
competitive and non-competitive
inhibition.
8.1 U.4 Metabolic pathways can be controlled by
end-product inhibition.
8.1 A.1 End-product inhibition of the pathway that
converts threonine to isoleucine.
8.1 A.2 Use of databases to identify potential new
anti-malarial drugs.
8.1 S.1 Calculating and plotting rates of reaction
from raw experimental results.
8.1 S.2 Distinguishing different types of inhibition
from graphs at specified substrate
concentration.

3. • Metabolism: the sum total of
all chemical reactions that
occur within an organism.
• Two types of metabolic
pathways
1. Linear Metabolic Pathways:
•Chemical changes in living things
often occurring with a number of
intermediate stages.
•Each stage has its own enzyme.
•Catabolic pathways breakdown
molecules
•Anabolic pathways build up
molecules
8.1 U.1 Metabolic pathways consist of chains and cycles of enzyme-
catalysed reactions.

4. 2. Cyclic Metabolic Pathways:
•The initial substrate is fed into the
cycle.
• Enzyme (a) combines the
regenerated Intermediate 4 to
catalyzes the production of
intermediate 1
• Enzyme (b) converts
intermediate 1 to intermediate 2
• Enzyme (c) converts
intermediate 2 to intermediate
3. The product is formed and
removed.
• Enzyme (d) converts
intermediate 3 to intermediate 4
and the cycle repeats.

5. 8.1 U.2 Enzymes lower the activation energy of the chemical reactions
that they catalyzed.
Activation energy: the initial input of energy that is required to trigger a
chemical reaction.
un-catalyzed reaction
catalyzed reaction
http://www.ib.bioninja.com.au/_Media/exergonic_reaction_med.jpeg
Enzymes benefit organisms by speeding up the rate at which reactions occur,
they make them happen millions of times faster.
The key effect enzymes have upon reactions

6. 8.1 U.2 Enzymes lower the activation energy of the chemical reactions
that they catalyze.
• The substrate binds to the enzymes’ active site and the active site is altered reaching
the transition state (the enzyme-substrate complex).
• Due to the binding the bonds in the substrate molecule are stressed/become less
stable.
• The binding lowers the overall energy level of the transition state.
• The activation energy of the reaction is then becomes reduced.
How do enzymes lower the activation energy of a reaction?
http://en.wikipedia.org/wiki/Image:Induced_fit_diagram.png

7. • Inhibitors are substances that reduce or completely stop the action of
an enzyme
• Inhibition can act on the active site (competitive) or on another
region of the enzyme molecule(non-competitive). The competition in
the former being for the active site of the enzyme.
8.1 U.3 Enzyme inhibitors can be competitive or non-competitive.

8. Competitive Inhibition
•The substrate and inhibitor are chemically
very similar in molecular shape.
•The inhibitor can bind to the active site
•Enzyme-inhibitor complex blocks
substrate from entering the active site.
•This blockage reduces the rate of
reaction.
However..
•If the substrate concentration is increased
it occupies more active sites than the
inhibitor. Therefore the substrate out-
competes the inhibitor for the active
site.
•The rate of reaction will increase again.
8.1 U.3 Enzyme inhibitors can be competitive or non-competitive.

9. Non-Competitive inhibition
•The substrate and the inhibitor are
chemically different in molecular
structure.
•The inhibitor cannot bind to the
active site.
•The inhibitor can bind to another
region of the enzyme molecule.
•The bonding of the inhibitor with
the enzyme causes structural
changes in the enzyme molecule.
•The active site changes shape.
•The substrate cannot bind therefore
the rate of reaction decreases.

10. 8.1 S.2 Distinguishing different types of inhibition from graphs at
specified substrate concentration.
https://wikispaces.psu.edu/download/attachments/46924781/image-6.jpg
Rate of reaction is reduced
Features of competitive inhibitors
When the concentration of substrate
begins to exceed the amount of
inhibitor, the maximum rate of the
uninhibited enzyme can be achieved.
However, it takes a much higher
concentration of substrate to achieve
this maximum rate.

11. https://wikispaces.psu.edu/download/attachments/46924781/image-6.jpg
Rate of reaction is reduced
Features of non-competitive inhibitors
It takes approximately the same
concentration of enzyme to reach the
maximum rate, but the maximum
rate is lower than the uninhibited
enzyme.
• The binding of the non-competitive inhibitor prevents
some of the enzymes from being able to react regardless
of substrate concentration.
• Those enzymes that do not bind inhibitors follow the
same pattern as the normal enzyme.
8.1 S.2 Distinguishing different types of inhibition from graphs at
specified substrate concentration.

12. 8.1 A.1 End-product inhibition of the pathway that converts threonine to isoleucine.
http://www.uic.edu/classes/bios/bios100/lecturesf04am/feedback-inh.gif
Isoleucine is an essential amino acid*
• Bacteria synthesize isoleucine from
threonine in a series of five
enzyme-catalysed steps
• As the concentration of isoleucine
increases, some of it binds to the
allosteric site of threonine
deaminase
• Isoleucine acts as a non-
competitive inhibitor to threonine
deaminase
• The pathway is then turned off,
regulating isoleucine production.
• If the concentration of isoleucine
later falls (as a result of its use)
then the allosteric sites of
threonine deaminase are emptied
and the enzymes recommences
the conversion of threonine to
isoleucine takes place.

13. 8.1 A.2 Use of databases to identify potential new anti-malarial drugs.
http://upload.wikimedia.org/wikipedia/commons/0/02/Mosquito_bite4.jpg
• Malaria is a
disease caused by
the pathogen
Plasmodium
falciparum.
• This protozoan uses
mosquitoes as a host
as well as humans
and hence can be
passed on by
mosquito bites

14. • In one study, approx. 300,000
chemicals were screened against
a chloroquine-sensitive 3D7
strain and the chloroquine-
resistant K1 strain of P.
falciparum.
• Other related and unrelated
organisms, including human cell
lines, were also screened.
• (19) new chemicals that inhibit
the enzymes normally targeted
by anti-malarial drugs were
identified
• Additionally (15) chemicals that
bind to malarial proteins were
identified – this can help in the
location of P. falciparum
• These results indicate possible
new directions for drug research.
Increasing drug resistance to anti-malarial drugs has lead to the use of bioinformatics and
chemogenomics to try and identify new drugs.
8.1 A.2 Use of databases to identify potential new anti-malarial drugs.

15. • Sometimes when a chemical binds to a target site, it can significantly alter
metabolic activity.
• Massive libraries of chemicals are tested individually on a range of related
organisms.
• For each organism a range of target sites are identified.
• A range of chemicals which are known to work on those sites are tested.
Bioinformatics is an approach whereby
multiple research groups can add information to a
database enabling other groups to query the
database.
Bioinformatics has facilitated research into metabolic pathways is
referred to as chemogenomics.

16. 8.1 S.1 Calculating and plotting rates of reaction from raw experimental
results.
The rate of reaction can be calculated using the formula:
Rate of reaction (s-1) = 1 / time taken (s)
Time taken in enzyme experiments this is commonly the time to reach a measurable end
point or when a standard event, caused by the enzyme reaction, has come to pass. This is
usually measured by the effects of the accumulation of product, but can as easily be
measured by the disappearance of substrates.
http://www.scienceexperimentsforkids.us/wp-content/uploads/2011/08/hydrogen-experiments-for-kids-3-img.jpg
Use the results from it or data from one of your
enzyme inhibition labs to calculate the rate of
reaction.
Enzyme inhibition can be investigated using these two
outlines by Science & Plants for Schools:
• The effect of end product, phosphate, upon the
enzyme phosphatase
• The inhibition of catechol oxidase by lead

17. 2.6 Structure of DNA and RNA
Essential idea: The structure of DNA allows efficient storage of
genetic information.

18. Understandings, Applications and Skills
Statement Guidance
2.6 U.1 The nucleic acids DNA and RNA are polymers of
nucleotides.
2.6 U.2 DNA differs from RNA in the number of strands
present, the base composition and the type of
pentose.
2.6 U.3 DNA is a double helix made of two antiparallel
strands of nucleotides linked by hydrogen
bonding between complementary base pairs.
2.6 A.1 Crick and Watson’s elucidation of the structure
of DNA using model making.
2.6 S.1 Drawing simple diagrams of the structure of
single nucleotides of DNA and RNA, using circles,
pentagons and rectangles to represent
phosphates, pentose and bases.
In diagrams of DNA structure, the helical
shape does not need to be shown, but the
two strands should be shown antiparallel.
Adenine should be shown paired with
thymine and guanine with cytosine, but the
relative lengths of the purine and pyrimidine
bases do not need to be recalled, nor the
numbers of hydrogen bonds between the
base pairs.

19. 2.6 U.1 The nucleic acids DNA and RNA are polymers of nucleotides.
A nucleotide: a single unit of a nucleic acid
There are two types of nucleic acid: DNA and RNA.
Nucleic acids are very large
molecules that are constructed by
linking together nucleotides to
form a polymer.

20. covalent bond
covalent bond
A nucleotide: a single unit of a nucleic acid
• five carbon atoms = a pentose
sugar
• If the sugar is Deoxyribose the
polymer is Deoxyribose Nucleic
Acid (DNA)
• If the sugar Ribose the polymer is
Ribose Nucleic Acid (RNA)
• acidic
• negatively
charged
• contains nitrogen
• has one or two rings
in it’s structure

21. 2.6 U.1 The nucleic acids DNA and RNA are polymers of nucleotides.

23. 2.6 U.1 The nucleic acids DNA and RNA are polymers of nucleotides.
• Nucleotides a linked into a
single by condensation
reaction
• Bonds are formed between the
phosphate of one nucleotide
and the pentose sugar of the
next.
• The phosphate group (attached
to the 5'-C of the sugar) joins
with the hydroxyl (OH) group
attached to the 3'-C of the
sugar
• Successive condensation
reactions between nucleotides
results in the formation of a
long single strand

24. RNA DNA
Bases
Adenine (A)
Guanine (G)
Uracil (U)
Cytosine (C)
Adenine (A)
Guanine (G)
Thymine (T)
Cytosine (C)
Sugar
Ribose Deoxyribose
Number of strands
Single stranded, and often,
but not always, linear in
shape
Two anti-parallel,
complementary strands
form a double helix
2.6 U.2 DNA differs from RNA in the number of strands present, the
base composition and the type of pentose.
http://commons.wikimedia.org/wiki/File:RiboseAndDeoxy.gif

25. 2.6 U.3 DNA is a double helix made of two antiparallel strands of nucleotides linked by
hydrogen bonding between complementary base pairs.
• DNA is double stranded and shaped
like a ladder, with the sides of the
ladder made out of repeating
phosphate and deoxyribose sugar
molecules covalently bonded
together. The two strands are
antiparallel to each other.
• The rungs of the ladder contain two
nitrogenous bases (one from each
strand) that are bonded together by
hydrogen bonds.
• The nitrogenous bases match up
according the Chargaff’s Rules in
which adenine always bonds to
thymine, and guanine always bonds
with cytosine. These bonds are
hydrogen bonds.

26. 2.6 S.1 Drawing simple diagrams of the structure of single nucleotides of
DNA and RNA, using circles, pentagons and rectangles to represent
phosphates, pentoses and bases.
Use this simple, but very
effective You Tube video to
learn how to draw the
nucleotides making up a
short section of a DNA
molecule.
To make sure you have
learn this skill you need to
practice it repeatedly.
http://youtu.be/kTH13oI8BSI

27. 2.6 A.1 Crick and Watson’s elucidation of the structure of DNA using
model making.
http://scarc.library.oregonstate.edu/coll/nonspcoll/catalog
ue/picture-dnamodel-900w.jpg
While others worked using an experimental basis Watson and
Crick used stick-and-ball models to test their ideas on the
possible structure of DNA. Building models allowed them to
visualize the molecule and to quickly see how well it fitted the
available evidence.
It was not all easy going however. Their first model, a triple helix,
was rejected for several reasons:
• The ratio of Adenine to Thymine was not 1:1 (as discovered
by Chargaff)
• It required too much magnesium (identified by Franklin)
From their setbacks they realized:
• DNA must be a double helix.
• The relationship between the bases and base pairing
• The strands must be anti-parallel to allow base pairing to
happen
Because of the visual nature of their work the second and the
correct model quickly suggested:
• Possible mechanisms for replication
• Information was encoded in triplets of bases

28. http://www.nobelprize.org/educational/medicine/dna_double_helix/readmore.html
http://youtu.be/sf0YXnAFBs8
Find out more about the discovery of DNA:
Watson and Crick gained Nobel prizes for
their discovery. It should be remembered
that their success was based on the
evidence they gained from the work of
others. In particular the work of Rosalind
Franklin and Maurice Wilkins, who were
using X-ray diffraction was critical to their
success.
2.6 A.1 Crick and Watson’s elucidation of the structure of DNA using
model making.

29. Bibliography / Acknowledgments
Jason de Nys