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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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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


Rna level transcription rate

Inside every organism

food

intake

Robust

Organs

Tissues

Cells

Molecules

Efficient

Evolvable


Rna level transcription rate

Catabolism

Precursors

Carriers

Inside every cell

Sugars

Amino Acids

Nucleotides

Fatty acids

Co-factors


Rna level transcription rate

Sugars

Biosynthesis

Fatty acids

Massively autocatalytic

Co-factors

Precursors

Amino Acids

Nucleotides

Transc.

RNA

xRNA

RNA level/ Transcription rate

RNAp

Gene

DNA level


Rna level transcription rate

Precursors

Catabolism

AA

AA

Nucl.

Transc.

RNA

xRNA

RNAp

Gene


Rna level transcription rate

Precursors

Catabolism

AA

AA

transl.

Enzymes

Nucl.

tRNA

Ribosome

mRNA

ncRNA

Transc.

RNA

xRNA

RNAp

Gene


Rna level transcription rate

Precursors

Catabolism

AA

AA

transl.

Enzymes

Nucl.

tRNA

Ribosome

Autocatalysis everywhere

transc.

RNA

xRNA

RNAp


Rna level transcription rate

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


Rna level transcription rate

reactions

products

reaction3

All products feedback everywhere

These won’t be drawn in detail

Proteins

trans.

ncRNA

Transc.


Rna level transcription rate

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


Rna level transcription rate

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


Rna level transcription rate

products

reactions

S

P

Reaction rate

reaction3

Enz1

Enz2

Enzyme form/activity

Running only the top layers

Mature red blood cells live 120 days


Rna level transcription rate

Diverse

Application

Diverse applications and genomes

Diverse

Genome


Rna level transcription rate

Eukaryotes

Animals

Fungi

Plants

Archaea

Bacteria

Algae

Horizontal gene transfer

HGT and

Shared Protocols

What is locus of early evolution?


Rna level transcription rate

Eukaryotes

Animals

Fungi

Plants

Archaea

Bacteria

Algae

Horizontal gene transfer

HGT and

Shared Protocols

Gene

DNA level

Controlled,

dynamic


Rna level transcription rate

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


Rna level transcription rate

Catabolism

Precursors

Carriers

Core metabolism

Sugars

Amino Acids

Nucleotides

Fatty acids

Co-factors


Rna level transcription rate

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


Rna level transcription rate

Core metabolism

Sugars

Catabolism

Protocols

Amino Acids

Precursors

Nucleotides

Fatty acids

Co-factors

Carriers

Constraints that deconstrain


Rna level transcription rate

Catabolism

Precursors

Carriers

Core metabolism

Sugars

Amino Acids

Nucleotides

Fatty acids

Co-factors


Rna level transcription rate

Catabolism

Precursors

Carriers


Rna level transcription rate

Gly

G1P

G6P

F6P

F1-6BP

Gly3p

ATP

13BPG

3PG

TCA

Oxa

ACA

2PG

PEP

Pyr

NADH

Cit

Catabolism


Rna level transcription rate

Gly

G1P

G6P

F6P

F1-6BP

Gly3p

13BPG

3PG

TCA

Oxa

ACA

2PG

PEP

Pyr

Cit

Precursors

metabolites


Rna level transcription rate

Gly

G1P

G6P

Enzymatically catalyzed reactions

F6P

F1-6BP

Gly3p

13BPG

3PG

TCA

Oxa

ACA

2PG

PEP

Pyr

Cit


Rna level transcription rate

Gly

G1P

G6P

Precursors

F6P

Autocatalytic

F1-6BP

Gly3p

Carriers

ATP

13BPG

3PG

TCA

Oxa

ACA

2PG

PEP

Pyr

NADH

Cit


Rna level transcription rate

Gly

G1P

G6P

Regulatory

F6P

F1-6BP

Gly3p

ATP

13BPG

3PG

TCA

Oxa

ACA

2PG

PEP

Pyr

NADH

Cit


Rna level transcription rate

Gly

G1P

G6P

F6P

F1-6BP

Gly3p

13BPG

3PG

TCA

Oxa

ACA

2PG

PEP

Pyr

Cit


Rna level transcription rate

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


Stoichiometry or mass and energy balance

Internal

Products

Nutrients

Stoichiometry or mass and energy balance

Biology is not a graph.


Stoichiometry plus regulation

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 (?!?)


Rna level transcription rate

Gly

G1P

G6P

F6P

F1-6BP

Gly3p

ATP

13BPG

3PG

TCA

Oxa

ACA

2PG

PEP

Pyr

NADH

Cit

S

Stoichiometry matrix


Rna level transcription rate

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


Rna level transcription rate

Gly

G1P

G6P

F6P

F1-6BP

form/activity

Gly3p

Allosteric regulation of enzymes

ATP

13BPG

3PG

TCA

Oxa

ACA

2PG

PEP

Pyr

NADH

Cit


Rna level transcription rate

Gly

G1P

G6P

rate

F6P

form/activity

F1-6BP

Gly3p

level

ATP

13BPG

3PG

TCA

Oxa

ACA

2PG

PEP

Pyr

NADH

Cit


Rna level transcription rate

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


Rna level transcription rate

Reaction rate

rate

Enzyme form/activity

form/activity

Proteins

level

Enzyme level/

Translation rate

Control

of

protein

levels

RNAs

DNAs


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


Rna level transcription rate

Transcription

Transc.

RNA

xRNA

RNA level/ Transcription rate

RNAp

Gene

DNA level


Rna level transcription rate

product

RNA level

Enz

Controlled,

dynamic

Transc.

RNA

xRNA

RNA level/ Transcription rate

RNAp

Gene

DNA level


Rna level transcription rate

Precursors

Enzyme level/

Translation rate

AA

trans.

Enzymes

AA

Nucl.

tRNA

mRNA

ncRNA

Transc.

RNA

xRNA

RNA level/ Transcription rate

RNAp

Gene

DNA level


Rna level transcription rate

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


Rna level transcription rate

What to call the sublayers?

Reactionrate

Enzymeform/activity

rate

Enzymelevel/

Translationrate

form/activity

level

RNAform/activity

RNAlevel/Transcription rate

What is where


Rna level transcription rate

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


Rna level transcription rate

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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