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Function-Process Links and Intermediary Metabolism*

Function-Process Links and Intermediary Metabolism*. We start with the big picture. * or How I Learned to Live with OBO-EDIT2. GO MF. GO BP. GO CC. Gene Product. Life.

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Function-Process Links and Intermediary Metabolism*

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  1. Function-Process Links and Intermediary Metabolism* We start with the big picture.... * or How I Learned to Live with OBO-EDIT2

  2. GO MF GO BP GO CC Gene Product Life.. a potentially self-perpetuating open system of linked organic reactions, catalyzed stepwise and almost isothermally by complex and specific organic catalysts which are themselves produced by the system. Morowitz 1991 Beginnings of Cellular Life

  3. The Point of Coupled Enzyme Reactions • Enzymes exist to catalyze the reactions • The enzyme requirement places the “graph” under genetic control

  4. Isomerizations • Binary Reactions • Condensation and • splitting reactions Types of Biochemical Reactions • oxidation and reduction • eg, alcohol <-> aldehyde • NAD/NADH • addition and removal of water • hydrolysis • condensation • movement of functional groups with or between molecules • phosphorylation, methylation • bond-breaking reactions • carbon-carbon bond breaking

  5. Types of Enzyme Activities

  6. A + B -> C+D D + E -> F + G C + X -> M + N substrate-product linkage of some GO enzyme functions Biochemical Pathways • What IS a Pathway? • a set of reactions that are linked or coupled via product-substrate relationships • beginning and an end Common metabolites can link pathways

  7. Reactants like ATP, water, NAD, etc. entering into many reactions are usually represented as multiple nodes Typical Boehringer Mannheim Metabolic Chart

  8. “The metabolic chart plays a role in biochemistry analogous to that of the periodic table of elements in inorganic chemistry”

  9. Selected Pathways • glycolysis • TCA cycle • purine biosynthesis • pyrimidine biosynthesis • pentose-phosphate shunt • glyoxylate cycle • fatty acid degradation • fatty acid biosynthesis • shikimate biosynthesis • chorismate biosynthesis • Using • Berg, Tymoczko, & Stryer's Biochemistry • Ables, Frey, & Jenks Biochemistry • Conn & Stumpf Outlines of Biochemistry • EC and Wikipedia

  10. Start End Defining the beginning and end

  11. GO:0006096 Glycolysis

  12. GO:0006099

  13. GO:0006097

  14. GO: 0006207

  15. GO:0006098

  16. GO:0000050

  17. Can we automate this or mine existing resources? • Reactome • Metacyte • EC • Kegg

  18. Might be some problems No link to de novo IMP biosynthesis Incomplete dbxrefs?

  19. Too many dbxrefs! manual

  20. Less than helpful • glycolysis has_part ... all of the glycolytic enzyme activities: informative • “carbohydrate metabolism” also has_part ... all of the glycolytic enzyme activities: duh • computationally correct

  21. What is included.. (choosing the starts and stops and side feeds)‏ Included in reactome set

  22. Closing thoughts

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