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3. What happens to the number of modes when I change a metabolite from internal to

external? Why does this happen?

4. What happens to the number of modes if I set all metabolites from external to inter­

nal? Why does this happen?

5. What happens to the number of modes when I change an enzyme from irreversible

to reversible? Why does this happen?

6. What happens to the number of modes if I change all the enzymes from reversible

to irreversible? Why does this happen?

Task 4.7

Perform elementary mode analysis for pyrimidine metabolism. In doing so, compare the

metabolism between humans and S. aureus. Proceed according to Example 4.6 and answer

the following questions:

1. How many modes do I get in humans and S. aureus?

2. Are there differences in pyrimidine metabolism between humans and S. aureus?

3. How do I interpret my found fashions in terms of finding drugs/points of attack

against diseases?

Useful Tools and Web Links

Database Information on metabolism can be found, for example, in the KEGG database

(https://www.genome.jp/kegg/), Roche Biochemical Pathways (https://www.roche.

com/sustainability/what_we_do/for_communities_and_environment/philanthropy/

science_education/pathways.htm) and EcoCyc (https://ecocyc.org/). Since 2020,

KEGG now has a new small grey box “change pathway type” in the upper left

corner, which shows the selection of available enzymes for an organism (green

boxes), missing ones are shown in white

Software A tutorial about Metatool can be found at: https://pinguin.biologie.uni-­jena.de/

bioinformatik/networks/metatool/metatool5.0/metatool5.0.html. Also important

are YANA (https://www.bioinfo.biozentrum.uni-­wuerzburg.de/computing/

yanasquare/), YANAsquare (https://www.bioinfo.biozentrum.uni-­wuerzburg.de/

computing/yanasquare/), COPASI (https://copasi.org/) and CellNetAnalyzer

(https://www2.mpi-­magdeburg.mpg.de/projects/cna/cna.html)

Literature

Ampattu BJ, Hagmann L, Liang C et al (2017) Transcriptomic buffering of cryptic genetic variation

contributes to meningococcal virulence. BMC Genomics 18(1):282

Bergmann FT, Sahle S, Zimmer C (2016) Piecewise parameter estimation for stochastic models

in COPASI.  Bioinformatics 32(10):1586–1588. https://doi.org/10.1093/bioinformatics/btv759

(PubMed PMID: 26787664)

4  Modeling Metabolism and Finding New Antibiotics