Transcript Topic 8.1 Metabolism - Cougar science rocks!

Skill: Distinguishing different types of inhibition from
graphs at specified substrate concentration
Red line = competitive inhibition
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when substrate exceeds inhibitor concentration,
max rate can be achieved, but takes much higher
substrate conc to achieve it
Blue line = noncompetitive inhibition
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enzyme doesn’t reach same max rate because
inhibitor prevents some enzymes from reacting
regardless of sub conc
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follow same pattern as with no inhibitor
takes same conc of enzyme to reach max rate, but
max rate is lower than uninhibited enzyme
APP: End-product inhibition of the pathway that converts
threonine to isoleucine
• Amino acid threonine is converted to
isoleucine
• Series of 5 rxns
• As conc. of iso builds up, it binds to
allosteric site of 1st enzyme in chain
(threonine deaminase)
• Iso acts as non-comp inhibitor
NOS: Developments in scientific research follow improvements in computing:
Developments in bioinformatics, such as the interrogation of databases,
have facilitated research into metabolic pathways
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BIOINFORMATICS – multiple research groups can add info to a
database, enabling other groups to query the database
Chemogenomics = bioinformatics technique for researching
metabolic pathways
E.g. scientists developing new drugs test massive libraries of
chemicals individually on a range of related organisms
When a drug binds to a target site, it can alter metabolic activity
For each organism a range of target sites are identified and
range of chemicals which are known to work on those sites are
tested
Chemogenomics = “the chemical universe tested against the
target universe”
App: Use of databases to identify potential new anti-malarial drugs
Malaria = blood-borne disease caused by Plasmodium falciparum, carried by mosquito
3 reasons we need new drugs:
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Increasing resistance
Narrow range of medicines
Global efforts to eradicate malaria
Research:
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P. Falciparum strain 3D7 genome sequenced
310,000 chemicals screened against 3D7 & K1 (resistant) to see if chems inhibite metabolism
Related & unrelated organisms also screened (incl humans)
Results of research:
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ID of 19 new chems that act as inhibitors
15 chems that bind to total of 61 different malarial proteins
Bioinformatics provided for scientists to continue study
Skill: Calculating & plotting rates of rxn from raw
experimental results
How to determine rate of enzyme-controlled rxn?
• Measure rate of disappearance of substrate
• Measure rate of appearance of a product
May require conversion of units to yield a rate unit
which should include s-1
DBQ p378 & 379
NOS: Paradigm shifts:
The chemiosmotic theory produced a paradigm shift in the field of bioenergetics
Peter Mitchell Nobel Prize Banquet Speech:
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…in the experimental sciences, the scientific fraternity must test a
new theory to destruction, if possible. Meanwhile, the originator of a
theory may have a very lonely time, especially if his colleagues find
his views of nature unfamiliar, and difficult to appreciate.
The final outcome cannot be known, either to the originator of a new
theory, or to his colleagues and critics, who are bent on falsifying it.
Thus, the scientific innovator may feel all the more lonely and
uncertain.
On the other hand, faced with a new theory, the members of the
scientific establishment are often more vulnerable than the lonely
innovator. For, if the innovator should happen to be right, the ensuing
upheaval of the established order may be very painful and
uncongenial to those who have long committed themselves to
develop and serve it. Such, I believe, has been the case in the field of
knowledge with which my work has been involved.
Naturally, I have been deeply moved, and not a little astonished, by
the accidents of fortune that have brought me to this point…
• Bioenergetics = study of energy flow
through living organisms
• Peter Mitchell, 1961 – proposed
chemiosmotic hypothesis to explain the
coupling of electron & H+ transport in
mitochondria to ATP synthesis
• Hypothesis was radical departure from
previous hypothesis, accepted only after
many years
• Awarded Nobel Prize for Chemistry in 1978
SKILL: Annotation of a diagram to indicate the adaptations of a
mitochondrion to its function
LET’S DO ACTIVITY P 387!
App: Electron tomography used to produce images of
active mitochondria
• Electron tomography – technique that allows 3D
images of interior of organelles
• beam of electrons is passed through sample at incremental
degrees of rotation around center of target sample,
assembling 3D image
• Leader: Dr. Carmen Mannella – “cristae are not simple
infoldings but are invaginations, defining micro-compartments in the
organelle. The membranes are not only very flexible but also dynamic.”
• Inner membrane is dynamic! = intermembrane space
increases in volume when mito is active in e- transport
NOS: Developments in scientific research follow improvements in apparatus:
Sources of 14C & autoradiography enabled Calvin to elucidate
the pathways of carbon fixation
• Sometimes progress in bio research suddenly becomes possible
because of other discoveries!
• Kamen & Ruben discovered 14C in 1945
• Half-life of 14C makes it ideal for use in tracing pathways of
photosynthesis
Melvin Calvin’s “lollipop apparatus”
1. algae growing in lollipop
2. replaced 12CO2 with 14CO2
3. Took samples of algae at very short time intervals to find what % of C
compounds contained 14C
Calvin used radioactive C as a tracer to see where it goes
during the light-independent rxn, hence figured out the
order of products in the Calvin Cycle!
App: Calvin’s experiment to elucidate the carboxylation of
RuBP
HTTP://IB.BIONINJA.COM.AU/HIGHER-LEVEL/TOPIC-8-METABOLISM-CELL/UNTITLED-2/CALVINCYCLE.HTML
Skill: Annotation of a diagram to indicate the adaptations of a
chloroplast to its function
Structure determines function!
Chloroplasts absorb light.
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Large SA of thylakoid membranes allows for large amount of light-absorption
Leaves in sun have deep grana, allowing more light to be absorbed
Chloroplasts produce ATP by photophosphorylation.
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Small volume inside thylakoids, so proton gradient develops quickly
Chloroplasts carry out the many chem rxns of the Calvin cycle.
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Stroma is compartment in which enzymes needed for Calvin cycle are kept
together with their substrates and products, so this concentration speeds up
cycle
ATP & NADPH needed for Calvin cycle are easily available because the
thylakoids where they are made are distributed throughout the stroma.