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Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute of Bioinformatics Swiss-Prot, Geneva StarOmics course Nov. 19-23
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Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

Dec 25, 2015

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Page 1: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways

Kristian Axelsen, Alan Bridge

Elisabeth Coudert & Anne Morgat

SIB Swiss Institute of BioinformaticsSwiss-Prot, Geneva

StarOmics course Nov. 19-23

Page 2: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

2, StarOmics course,Lausanne, Monday November 19th

http://education.expasy.org/cours/StarOmics2012/

Page 3: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

3, StarOmics course,Lausanne, Monday November 19th 3

Metabolism of living organisms can be apprehended as a network of biochemical reactions, connected by the chemical compounds involved in these reactions and generally catalyzed by enzymes.

Page 4: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

4, StarOmics course,Lausanne, Monday November 19th

Thymidine kinase is a phosphotransferase. It catalyzes the reversible phosphorylation of thymidine (2'-deoxythymidine) to dTMP (2'-deoxythymidine monophosphate) using ATP as phosphoryl donor.

4

Page 5: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

5, StarOmics course,Lausanne, Monday November 19th

Enzyme nomenclature

5

• By the late 1950's it had become evident that the nomenclature of enzymology, in the absence of any guiding authority, in a period when the number of known enzymes was increasing rapidly, was getting out of hand.

• The General Assembly of the International Union of Biochemistry (IUB) decided, during the third International Congress of Biochemistry in Brussels in August, 1955, to set up an International Commission on Enzymes. This step was taken in consultation with the International Union of Pure and Applied Chemistry (IUPAC).

• The International Commission on Enzymes was established in 1956

Page 6: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

6, StarOmics course,Lausanne, Monday November 19th

Enzyme nomenclatureThe Nomenclature Committee of the IUBMB (International Union of Biochemistry and Molecular Biology) is trying to categorise all known enzymes and to formalise their nomenclature.

6

http://www.chem.qmul.ac.uk/iubmb/

Page 7: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

7, StarOmics course,Lausanne, Monday November 19th

1= Oxidoreductases2= Transferases3= Hydrolases4= Lyases5= Isomerases6= Ligases

• The 1st digit = Enzyme class Depends on the type of the catalyzed reaction• The 2nd digit = Subclass Defined by the reaction mechanism• The 3rd digit = Subsubclass Indicates the nature of the molecules involved• The 4th digit = Serial number

Transferase

Transferring phosphorous-containing groups

Phosphotransferases with an alcohol group as acceptor

Thymidine kinase

.

Enzyme Commission number (EC number)

EC 1.2.3.4

EC 2.7.1.21 ATP + thymidine = ADP + thymidine 5'-phosphate

7

Page 8: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

8, StarOmics course,Lausanne, Monday November 19th

NC-IUBMB – enzyme nomenclature• The International Commission on Enzymes was established in 1956• Composed of 10 members; enzymologists and chemists (also 10 members

today)• Today members are also from databases: Brenda (Ida and Dietmar

Schomburg), KEGG (Masaaki Kotera), MetaCyc (Ron Caspi), and SIB (Kristian Axelsen)

• First printed version of the EC list 1961 (712 entries)• ENZYME db: First computer readable version of the EC list, April 1990

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Historical Introduction: http://www.chem.qmul.ac.uk/iubmb/enzyme/history.html

Page 9: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

9, StarOmics course,Lausanne, Monday November 19th

Development of ENZYME nomenclature

Page 10: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

10, StarOmics course,Lausanne, Monday November 19th

StarOmics training agenda

Page 11: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

11, StarOmics course,Lausanne, Monday November 19th

StarOmics training agenda

Page 12: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

12, StarOmics course,Lausanne, Monday November 19th

Major metabolic resources used during this training

• BioCyc / MetaCyc• KEGG• SIB / EBI biocuration effort• Gene Ontology• Swiss project: SystemX.ch / MetaNetX• European project: Microme

Page 13: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

13, StarOmics course,Lausanne, Monday November 19th 14 octobre 2008UJF Grenoble

http://biocyc.org

Page 14: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

14, StarOmics course,Lausanne, Monday November 19th

MetaCyc (http://metacyc.org/) is a database of manually curated non-redundant metabolic pathways supported by experimental evidence.

MetaCyc stores pathways involved in primary and secondary metabolism. This includes chemical compounds, reactions, proteins, protein complexes, and genes associated to these pathways

Stats of MetaCyc V16.1

MetaCyc

Page 15: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

15, StarOmics course,Lausanne, Monday November 19th 14 octobre 2008UJF Grenoble

http://www.genome.jp/kegg/

KEGG: Kyoto Encyclopedia of Genes and Genomes

• KEGG is an integrated database resource for the computational representation of biological systems from the integration of genomic and chemical information into molecular wiring diagrams of interaction, reaction and relation networks (systems information)

Page 16: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

16, StarOmics course,Lausanne, Monday November 19th

GENES (genomic

information)

LIGAND(chemical

information)

PATHWAY/BRITE(System information)

KO

Page 17: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

17, StarOmics course,Lausanne, Monday November 19th

SIB & EBI biocuration effort

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towards sytems biology…

Page 18: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

18, StarOmics course,Lausanne, Monday November 19th

UniProt: the Universal Protein resource

Since 2002 a merger and collaboration of three databases:

The mission of UniProt is to provide the scientific community with a comprehensive, high-quality and freely accessible resource of protein sequence and functional information.

Page 19: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

19, StarOmics course,Lausanne, Monday November 19th

http://www.uniprot.org/http://www.uniprot.org/

UniProt is updated and distributed every 4 weeks

It can be accessed online for searches or download at

Page 20: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

20, StarOmics course,Lausanne, Monday November 19th

• To support biological research by providing a freely accessible, stable, comprehensive, fully classified, richly and accurately annotated protein sequence knowledgebase, with extensive cross-references and querying interfaces.

• UniProt is comprised of four major components

UniProt mission

Page 21: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

21, StarOmics course,Lausanne, Monday November 19th

UniProt database growth

Page 22: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

22, StarOmics course,Lausanne, Monday November 19th

http://www.geneontology.org

Page 23: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

23, StarOmics course,Lausanne, Monday November 19th

http://www.ebi.ac.uk/GOA/

Page 24: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

24, StarOmics course,Lausanne, Monday November 19th

3 categories of GO terms

Page 25: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

25, StarOmics course,Lausanne, Monday November 19th

http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009507&session_id=9452amigo1349170795

Page 26: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

26, StarOmics course,Lausanne, Monday November 19th

~ 35’000 GO terms~12’000’000 gene products are linked to GO terms: but how ?

>96% of all annotations are inferred without direct manual curation !

Orthology, Paralogy and OntologiesChristoph DessimozThursday Nov. 22th

Page 27: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

27, StarOmics course,Lausanne, Monday November 19th

Importance of the ‘GO evidence tags’

Page 28: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

28, StarOmics course,Lausanne, Monday November 19th

GO annotation - manual‘GO annotators’ read publication and infer GO terms to the corresponding genes according to the information found in the paper.

Done by more than 30 external model organism and multi-species database curators including UniProtKB/Swiss-Prot, dictyBase, EcoCyc, FlyBase, Gramene, Human Protein Atlas, IntAct, LifeDB, MGI, PomBase, Reactome, RGD, TAIR, SGD, WormBase and ZFIN.

Link to the corresponding paper…(PubMed ID)

Page 29: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

29, StarOmics course,Lausanne, Monday November 19th

Histone H4: annotation according to paper content

Page 30: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

30, StarOmics course,Lausanne, Monday November 19th

Histone H4: annotation according to paper content : biological mistakes !

!!! Large scale derived data (‘proteome’)

Page 31: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

31, StarOmics course,Lausanne, Monday November 19th

Lack of consistency between species

Page 32: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

32, StarOmics course,Lausanne, Monday November 19th

Be careful…

Page 33: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

33, StarOmics course,Lausanne, Monday November 19th 33

http://www.metanetx.org/

• RTD project of SystemsX.ch– J. Stelling, – I. Xenarios, – W. Gruissem, – U. Sauer, – V. Hatzimanikatis– D. Kossmann– M. Pagni

Page 34: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

34, StarOmics course,Lausanne, Monday November 19th 34

A Knowledge-Based Bioinformatics Frameworkfor Microbial Pathway Genomics

www.microme.eu

Microme is an EU Framework Programme 7 Collaborative Project.

Microme is a resource for bacterial metabolism, whose aim is to support the large scale inference of metabolic flux directly from genome sequence.

Page 35: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

35, StarOmics course,Lausanne, Monday November 19th

StarOmics training agenda

• Introduction• Available

resources• Exercises

Page 36: Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge Elisabeth Coudert & Anne Morgat SIB Swiss Institute.

36, StarOmics course,Lausanne, Monday November 19th

http://education.expasy.org/cours/StarOmics2012/