Metabolic Network Analysis

Lecture series for master Bioinformatics or Mathematics dr. Sander Hille

shille@math.leidenuniv.nl http://www.math.leidenuniv.nl/~shille
Snellius, Niels Bohrweg 1, room 401
Mathematisch Instituut

Biochemistry

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Various biological networks

Metabolic networks Signaling networks Regulatory networks Their interconnection

Spring semester 2011

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Sander Hille

Spring semester 2011

Metabolic Nw. An. C-I

Biochemistry
One aspect that distinguishes bio(logical) chemistry from general chemistry:

Metabolic networks
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-- example: photosynthesis --

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Cell with chloroplasts

The chemical compounds used by biological systems represent only a tiny fraction of all possible chemical carbon-based compounds with molecular mass in the same range:
estimated: ~ 103 104 out of ~ 1060

Cross section

(Ch.M. Dobson (2004). Chemical space and biology, Nature 432, 824-828)

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Metabolic Nw. An. C-I

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Sander Hille

Spring semester 2011

Metabolic Nw. An. C-I

Metabolic networks
-- example: photosynthesis --

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Metabolic networks
-- example: glycolysis --

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Recall:

Chloroplasts in a moss, Plagiomnium affine (Photo: Kristian Peters) (http://www.biologyclass.net/pathways.html)

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Metabolic Nw. An. C-I

Metabolic networks
-- some characteristics -Almost all reactions are catalysed by enzymes
Flagellum ATP ADP

Signaling networks
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-- E. coli chemotaxis motor control -Chemotactic agent (aspartate)

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Example of an enzyme
Flagellum

Glucose
Hexokinase

G6P
Phosphoglucose isomerase

F6P

Receptor (Tar) Outer membrane

Periplasmic space

Plama membrane Molecular motor

Enzymes

Some reactions do not (hardly) occur in their absence Although chemically:

W A
ATP

R
p

W A
p

ATP

Y Z

Y
p

Control of direction of rotation

Principle of microscopic reversability

Large number of (substrate) molecules (7) Sander Hille
Quarternary structure of ATP-synthase = protein complex

ADP

Intra-cellular diffusion

B
Cytoplasm

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Metabolic Nw. An. C-I

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Sander Hille

Spring semester 2011

Metabolic Nw. An. C-I

Signaling networks
-- some characteristics -Small(er) number of molecules involved Limited number of type of reactions, e.g.: -- protein-protein -- polymerisation -- phospho-transfer
(by enzymes called kinases / phosphatases)
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Regulatory networks
-- the overall control -Implements decission-making on the basis of a perceived environment as realised by the signaling network(s). Acts over the cells DNA
Single molecule interaction Stochastic ( = random ) effects may play a role or may need to be controlled / reduced
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The signaling network creates a perceived environment inside the cell as different levels of signaling molecules (messengers) in possibly different compartments

Involves: Transcription Translation

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Sander Hille

Spring semester 2011

Metabolic Nw. An. C-I

Gene transcription
RNA polymerase - factor

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mRNA translation

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(Basics for prokaryotes eukaryotic transcription much more involved)

DNA

1
Bound transcription factor

2
RNA strand (mRNA)

3
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Regulatory networks
-- sporulation control in B. subtilis -Signal
ATP ADP

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Regulatory networks
-- sporulation control in B. subtilis -Part of signaling network
ATP

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Signal
ADP

KinA

KinA~P Spo0F
Spo0B~P kinA

KinA

KinA~P Spo0F
Spo0B~P

kinA H

Spo0F~P Spo0B

Spo0F~P Spo0B

Spo0A~P

Spo0A Regulatory feedback

spo0A
abrB AbrB

Spo0A~P

Spo0A

- abrB AbrB A

- A

H spo0A

A spo0H

+ A

H spo0F

A spo0H

+ A

H spo0F

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Metabolic Nw. An. C-I

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Metabolic Nw. An. C-I