Biology Reference
In-Depth Information
Chapter 12
Reconstruction of Genome-Scale
Metabolic Networks
Hooman Hefzi,
1
Bernhard O. Palsson
1
and Nathan E. Lewis
1
,
2
1
Bioengineering Department, University of California San Diego, La Jolla, CA, USA,
2
Department of Genetics, Harvard Medical School,
Boston, MA 02115, USA
Chapter Outline
Introduction
229
Stage 5: Data Assembly, Dissemination, and Use
237
Cellular Metabolism
229
Reconstruction Standards
237
Metabolic Reconstructions
230
Applications
237
The Reconstruction Process
230
Metabolic Engineering
237
E. coli Core Metabolism
230
Biological Discovery
239
Stage 1: Creation of a Draft Reconstruction
230
Phenotype Prediction and Evaluation
239
Stage 2: Manual Curation
231
Fundamental Properties of Biological Networks
240
Additional Information and Verification
231
A Context for the Analysis of Large Data Sets
241
Incorporation of Spontaneous and Transport Reactions
232
Multi-Cell and Microbial Community Metabolism
241
The Biomass 'Reaction'
233
Future Directions
242
Stage 3: Converting a Network to
a Mathematical Model
E-Matrix Reconstructions
242
233
O-Matrix Reconstructions
243
Stage 4: Network Evaluation
234
Toward a Whole Cell Model
244
Topological Tests
234
Glossary
244
Thermodynamic Tests
235
Acknowledgments
245
Phenotypic Tests
236
References
245
Quantitative Tests
236
INTRODUCTION
Metabolism and enzymes are the classic topics of discus-
sion in any undergraduate biochemistry course. Such text-
books are full of protein structures and descriptions of the
topology and properties of short pathways. However,
a living cell contains thousands of enzymes that do not act
in isolation. In like manner, pathways in a cell often have
complexity far beyond the simple organization shown in
a textbook. Metabolic reconstructions aim to move beyond
static pictures of protein structures and pathway concepts.
This is done when they are used to model the functions of
all enzymes in a cell, thus allowing us to understand how
these parts and their interactions function together as
a whole to make a living organism.
Cellular Metabolism
Cellular metabolism is organized around a large network
of enzyme-catalyzed and spontaneous chemical reactions.
These reactions involve a set of diverse metabolites, and
all of the reactions function together to produce and
recycle the materials for cell maintenance and growth
(e.g.. amino acids, lipids, ATP), signaling molecules (e.g.,
cAMP and H
2
S), waste products, and molecules that
affect the growth of surrounding organisms (e.g., antibi-
otics, quorum-sensing molecules, hormones, etc.).
Metabolism is important in most cell and organism
phenotypes. For example, it has been implicated as
a contributing factor of human diseases such as diabetes
[1]
and cancer
[2]
, making it an auspicious area for
