Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge...

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

2, StarOmics course,Lausanne, Monday November 19th

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

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.


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

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Enzyme nomenclature

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• 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


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.

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


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

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Enzyme Commission number (EC number)

EC 1.2.3.4

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

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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


Development of ENZYME nomenclature


StarOmics training agenda


Major metabolic resources used during this training

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

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

http://biocyc.org


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

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)


GENES (genomic

information)

LIGAND(chemical

information)

PATHWAY/BRITE(System information)

KO


SIB & EBI biocuration effort

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towards sytems biology…


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.


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


• 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


UniProt database growth


http://www.geneontology.org


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


3 categories of GO terms


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


~ 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


Importance of the ‘GO evidence tags’


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)


Histone H4: annotation according to paper content


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

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


Lack of consistency between species


Be careful…


http://www.metanetx.org/

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


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.



• Introduction• Available

resources• Exercises


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

Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge...

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Transcript of Introduction to metabolism: Compounds, Reactions, Enzymes and Pathways Kristian Axelsen, Alan Bridge...