Download • How to get rid of the RHP zero? • What are the new tradeoffs?

Control
x
y
•  How to get rid of the RHP zero?
•  What are the new tradeoffs?
Bacterial cell
Autocatalytic feedback
Precursors
Catabolism
Environment
cids
Fatty a
Co-factors
Amin
o Aci
ds
Genes
Carriers
Environment
DNA
replication
Huge
Variety
Trans*
Proteins
Nutrients
Core metabolism
Huge
Variety
Catabolism
Precursors
Nutrients
Taxis and
transport
Same
12
in all
Core metabolism
cells
Acids
o
n
i
m
A
Nucleotides
Fatty ac
ids
Carriers
Same
8
in all
cells
Gly
G1P
G6P
F6P
Reaction
F1-6BP
Err/flow ctrl
Gly3p
Mgmt
ATP
13BPG
3PG
2PG
NADH
Oxa
PEP
Pyr
ACA
TCA
Cit
Gly
G1P
G6P
F6P
F1-6BP
Gly3p
ATP
How does all this
feedback work?
13BPG
3PG
2PG
NADH
Oxa
PEP
Pyr
ACA
TCA
Cit
Gly
G1P
G6P
F6P
F1-6BP
Gly3p
ATP
ATP
13BPG
3PG
2PG
NADH
Oxa
PEP
Pyr
ACA
TCA
Cit
Autocatalytic
x
Control
y
F6P
F1-6BP
Gly3p
13BPG
3PG
ATP
Autocatalytic
x
Control
y
Autocatalytic
Control
[ATP]
1.05
1
h >> 1
0.95
Time response
0.9
Yet
fragile
0.85
h=1
0.8
15
20
e
r
o
Time
(minutes)
m
s
e
r
a
c
e
r
u
t
a
N
.
f
f
o
Note:
e
h
>>1
d
a
r
t
s
i
h
t
t
u
Spectrum
abo
0
5
10
0.8
Robust
Log(Sn/S0)
0.6
0.4
0.2
h=1
0
-0.2
-0.4
-0.6
-0.8
0
2
4
Frequency
6
8
10
output=x
C
+
Plant
Small z is bad.
Small z is bad
(oscillations and crashes)
Small z =
•  small k and/or
•  large q
Efficiency =
•  small k and/or
•  large q
Correctly predicts conditions
with “glycolytic oscillations”
x
rate
y
level
More enzyme
Autocatalytic
x
Control
y
q consumed
produced
Autocatalytic
x
Control
y
Layered control
rate
form/activity
level
Autocatalytic
x
Control
y
Enzyme
complexity
Autocatalytic
x
Control
y
Autocatalytic
x
Control
y
Small z =
•  small k and/or
•  large q
Efficiency =
•  small k and/or
•  large q
Autocatalytic
x
Control
y
•  How to get rid of the RHP zero?
•  What are the new tradeoffs?
Control
x
y
•  How to get rid of the RHP zero?
•  What are the new tradeoffs?
Control
x
y
•  How to get rid of the RHP zero?
•  What are the new tradeoffs?
More control
x
x
y
y
More
complex
enzymes