Pathways

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Pathways Molecules

• M.A. Ott (CMBI)

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Contents
M.A. Ott
Pathways and Molecules

• Enzymes and Metabolites
• Metabolic Pathways Cholesterol Biosynthesis
• Metabolic Disorders
• BioMeta Database

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Metabolite and Pathway Databases
M.A. Ott
Pathways and Molecules
http//www.genome.ad.jp/kegg/ http//www.brenda.un
i-koeln.de/ http//www.expasy.org/tools/pathways/
http//www.empproject.com/ http//metacyc.org/ htt
p//ecocyc.org/ http//www.ncgr.org/pathdb/ http/
/medicago.vbi.vt.edu/B-Net/ http//www.mol-net.de/
biopath/ http//www.ergo-light.com/ERGO/ http//ww
w.reactome.org/ http//www.chem.qmul.ac.uk/iubmb/e
nzyme/
Kyoto Encyclopedia of Genes and Genomes BRENDA
enzyme database ExPASy biochemical pathway EMP
enzymology and metabolism data MetaCyc metabolic
pathways EcoCyc E. coli genome and
metabolism PathDB biological pathways and
networks B-NET - Biochemical Network BioPath
C_at_ROL database ERGO comprehensive genome
analysis Reactome biological processes IUBMB
enzymes
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Metabolism and Friends
M.A. Ott
Pathways and Molecules

• Metabolism The reactions in organisms
• Anabolism Synthesis of larger biomolecules
  from smaller ones Usually requires
  energy input
• Catabolism Break down of larger molecules
  into smaller ones Usually releases energy

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Enzymes
M.A. Ott
Pathways and Molecules

• Virtually all metabolic reactions require
  enzymatic catalysis
• Rate enhancement factor can be up to 1015
• Enzymes are highly reaction-specific,
  catalyzing only one conversion
• Enzymes are substrate-specific, limiting their
  action to only one compound or to related
  compounds

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The Metabolic Network
M.A. Ott
Pathways and Molecules
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Some Metabolites
M.A. Ott
Pathways and Molecules

• Common metabolitesWater, NADH, ATP,
  Phosphate,
• End products of pathwaysVitamin B12, Urea,
  Penicillin, Ecdysone,
• Intermediates in pathwaysGlucose-6-P,
  Lanosterol, Precorrins, Shikimate,

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Common Metabolites ATP / ADP
M.A. Ott
Pathways and Molecules
Full structures
Shorthand
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Common Metabolites NADH / NAD
M.A. Ott
Pathways and Molecules
Full structures
Shorthand
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Common Metabolites
M.A. Ott
Pathways and Molecules
Water Ammonia Phosphate ATP, ADP NADH,
NAD NADPH, NADP FAD, FADH2 FMN, FMNH2 SAM,
SAH Coenzyme A Glutamate/2-Oxoglutarate
Phosphorylation Reduction/oxidation Reductio
n/oxidation Reduction/oxidation Reduction/oxidati
on Methyl group transfer Acyl group
transfer Amino/ketone group exchange
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Cholesterol Biosynthesis Outline
M.A. Ott
Pathways and Molecules
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Cholesterol Biosynthesis from Squalene
M.A. Ott
Pathways and Molecules
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Metabolic Disorders
M.A. Ott
Pathways and Molecules

• Inability to synthesize compoundsAbsence of
  important compounds
• Inability to degrade compoundsAccumulation of
  undesired waste productsE.g., in phenylketonuria

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Phenylketonuria (Error in Phenylalanine
Catabolism)
M.A. Ott
Pathways and Molecules
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The BioMeta Database
M.A. Ott
Pathways and Molecules
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BioMeta Database Structure
M.A. Ott
Pathways and Molecules
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BioMeta Database Structure
M.A. Ott
Pathways and Molecules
Reaction 1 Mol_1 Mol_2 lt-gt Mol_3
Mol_4 Reaction 2 Mol_2 Mol_3 --gt Mol_5
Mol_6 Reaction 3 2 Mol_6 --gt
Mol_7
R-M Links
Molecules
Reactions
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Sample Database Query
M.A. Ott
Pathways and Molecules

• ec_nr enzyme_name rxn_id rev role
  stoich name
• ---------------------------------------------
  -----------------
• 1.2.3.4 oxalate oxidase MR000247 i s
  1 Oxalic acid
• 1.2.3.4 oxalate oxidase MR000247 i s
  1 O2
• 1.2.3.4 oxalate oxidase MR000247 i p
  1 H2O2
• 1.2.3.4 oxalate oxidase MR000247 i p
  2 CO2

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Molecular Structures and Reactions
M.A. Ott
Pathways and Molecules

• Reactions balancing atoms charges
• adding direction/reversibility
• Molecules adding stereochemical configurations
• canonicalizing tautomeric form

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Alternative Pathways
M.A. Ott
Pathways and Molecules
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BioMeta Database
M.A. Ott
Pathways and Molecules

• Based on freely available data (KEGG Ligand
  database)
• Augmentation, completion and correction of
  small-molecule information - Adding missing
  stereochemistry to structures - Balancing atoms
  and charges in reactions - Establishing the
  reversibility and direction of reactions
• Search for alternative pathways between
  metabolites
• Search for missing enzymes

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BioMeta Things Being Done
M.A. Ott
Pathways and Molecules

• Enhancing compound/reaction structures
• Establishing directionality/reversibility of
  reactions
• Distinguishing cofactors/current/external/
  common metabolites from real metabolites
• Adding more compound data, e.g. pKa (curve)
• Building WWW interface

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BioMeta Things To Do
M.A. Ott
Pathways and Molecules

• Atom-to-atom correspondence (reaction mapping)
• Pathway search generation
• Cellular localization
• Enzyme species relations

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Acknowledgements
M.A. Ott
Pathways and Molecules

• Felix van Diggelen
• Gert Vriend
• CMBI