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RNA level/ Transcription rate

Reaction rate. rate. Enzyme form/activity. form/activity. Proteins. level. Enzyme level/ Translation rate. rate. form/activity. form/activity. RNAs. level. RNA level/ Transcription rate. rate. DNAs. Inside every organism. food intake. Robust. Organs Tissues Cells Molecules.

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RNA level/ Transcription rate

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  1. Reaction rate rate Enzyme form/activity form/activity Proteins level Enzyme level/ Translation rate rate form/activity form/activity RNAs level RNA level/ Transcription rate rate DNAs

  2. Inside every organism food intake Robust Organs Tissues Cells Molecules Efficient Evolvable

  3. Catabolism Precursors Carriers Inside every cell Sugars Amino Acids Nucleotides Fatty acids Co-factors

  4. Sugars Biosynthesis Fatty acids Massively autocatalytic Co-factors Precursors Amino Acids Nucleotides Transc. RNA xRNA RNA level/ Transcription rate RNAp Gene DNA level

  5. Precursors Catabolism AA AA Nucl. Transc. RNA xRNA RNAp Gene

  6. Precursors Catabolism AA AA transl. Enzymes Nucl. tRNA Ribosome mRNA ncRNA Transc. RNA xRNA RNAp Gene

  7. Precursors Catabolism AA AA transl. Enzymes Nucl. tRNA Ribosome Autocatalysis everywhere transc. RNA xRNA RNAp

  8. products reactions S P Reaction rate reaction3 Enz1 Enz2 Enzyme form/activity Enzyme level/ Translation rate tRNA trans. Enzymes AA Enz2 RNA form/activity ncRNA mRNA RNA level/ Transcription rate Transc. RNA xRNA Ribosome Gene RNAp

  9. reactions products reaction3 All products feedback everywhere These won’t be drawn in detail Proteins trans. ncRNA Transc.

  10. products reactions S P Reaction rate reaction3 Enz1 Enz2 Enzyme form/activity Enzyme level/ Translation rate tRNA trans. Enzymes AA Enz2 RNA form/activity ncRNA mRNA RNA level/ Transcription rate Transc. RNA xRNA Ribosome Gene RNAp

  11. reactions S P Reaction rate reaction3 Enz1 Enz2 Enzyme form/activity Enzyme level/ Translation rate tRNA trans. Enzymes AA RNA form/activity ncRNA mRNA RNA level/ Transcription rate Transc. RNA xRNA Ribosome Gene RNAp

  12. products reactions S P Reaction rate reaction3 Enz1 Enz2 Enzyme form/activity Running only the top layers Mature red blood cells live 120 days

  13. Diverse Application Diverse applications and genomes Diverse Genome

  14. Eukaryotes Animals Fungi Plants Archaea Bacteria Algae Horizontal gene transfer HGT and Shared Protocols What is locus of early evolution?

  15. Eukaryotes Animals Fungi Plants Archaea Bacteria Algae Horizontal gene transfer HGT and Shared Protocols Gene DNA level Controlled, dynamic

  16. Eukaryotes Animals Fungi Plants Archaea Bacteria Algae products reactions Reaction rate S P HGT and Shared Protocols reaction3 Enz1 Enz2 Enzyme form/activity Enzyme level/ Translation rate trans. Enzymes AA mRNA RNA form/activity Ribosome tRNA ncRNA RNA level/ Transcription rate Transc. RNA xRNA RNAp Gene

  17. Catabolism Precursors Carriers Core metabolism Sugars Amino Acids Nucleotides Fatty acids Co-factors

  18. Same 12 in all cells Taxis and transport Core metabolism Sugars Catabolism Amino Acids Nucleotides Precursors Nutrients Fatty acids • 100 • same in all • organisms Co-factors Carriers Same 8 in all cells Huge Variety

  19. Core metabolism Sugars Catabolism Protocols Amino Acids Precursors Nucleotides Fatty acids Co-factors Carriers Constraints that deconstrain

  20. Catabolism Precursors Carriers Core metabolism Sugars Amino Acids Nucleotides Fatty acids Co-factors

  21. Catabolism Precursors Carriers

  22. Gly G1P G6P F6P F1-6BP Gly3p ATP 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr NADH Cit Catabolism

  23. Gly G1P G6P F6P F1-6BP Gly3p 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr Cit Precursors metabolites

  24. Gly G1P G6P Enzymatically catalyzed reactions F6P F1-6BP Gly3p 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr Cit

  25. Gly G1P G6P Precursors F6P Autocatalytic F1-6BP Gly3p Carriers ATP 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr NADH Cit

  26. Gly G1P G6P Regulatory F6P F1-6BP Gly3p ATP 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr NADH Cit

  27. Gly G1P G6P F6P F1-6BP Gly3p 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr Cit

  28. If we drew the feedback loops the diagram would be unreadable. Gly G1P G6P F6P F1-6BP Gly3p ATP 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr NADH Cit

  29. Internal Products Nutrients Stoichiometry or mass and energy balance Biology is not a graph.

  30. Stoichiometry plus regulation  Matrix of integers  “Simple,” can be known exactly  Amenable to high throughput assays and manipulation  Bowtie architecture  Vector of (complex?) functions  Difficult to determine and manipulate  Effected by stochastics and spatial/mechanical structure  Hourglass architecture  Can be modeled by optimal controller (?!?)

  31. Gly G1P G6P F6P F1-6BP Gly3p ATP 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr NADH Cit S Stoichiometry matrix

  32. Gly G1P G6P F6P F1-6BP Gly3p Regulation of enzyme levels by transcription/translation/degradation 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr Cit level

  33. Gly G1P G6P F6P F1-6BP form/activity Gly3p Allosteric regulation of enzymes ATP 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr NADH Cit

  34. Gly G1P G6P rate F6P form/activity F1-6BP Gly3p level ATP 13BPG 3PG TCA Oxa ACA 2PG PEP Pyr NADH Cit

  35. Gly G1P Fast response G6P rate F6P Layered architecture form/activity F1-6BP Gly3p level ATP 13BPG Slow 3PG TCA Oxa ACA 2PG PEP Pyr NADH Cit

  36. Reaction rate rate Enzyme form/activity form/activity Proteins level Enzyme level/ Translation rate Control of protein levels RNAs DNAs

  37. Reaction rate rate Enzyme form/activity form/activity Proteins level Enzyme level/ Translation rate rate form/activity form/activity RNAs level RNA level/ Transcription rate rate DNAs

  38. Transcription Transc. RNA xRNA RNA level/ Transcription rate RNAp Gene DNA level

  39. product RNA level Enz Controlled, dynamic Transc. RNA xRNA RNA level/ Transcription rate RNAp Gene DNA level

  40. Precursors Enzyme level/ Translation rate AA trans. Enzymes AA Nucl. tRNA mRNA ncRNA Transc. RNA xRNA RNA level/ Transcription rate RNAp Gene DNA level

  41. products reactions Reaction rate S P reaction3 Enz1 Enz2 Enzyme form/activity Enzyme level/ Translation rate trans. Enzymes AA mRNA RNA form/activity Ribosome tRNA ncRNA RNA level/ Transcription rate Transc. RNA xRNA RNAp Gene

  42. What to call the sublayers? Reactionrate Enzymeform/activity rate Enzymelevel/ Translationrate form/activity level RNAform/activity RNAlevel/Transcription rate What is where

  43. Taxis and transport 12 Autocatalytic feedback Polymerization and complex assembly Core metabolism Sugars Fatty acids Precursors Co-factors Catabolism Nutrients Amino Acids Genes Proteins Nucleotides Carriers Trans* 8 100 Huge Variety DNA replication 104 to ∞ in one organisms

  44. Autocatalytic feedback Few polymerases Highly conserved Polymerization and complex assembly Genes Proteins Trans* DNA replication 104 to ∞ in one organisms Huge Variety

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