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Chapter 15

Design of metabolism

http://www.chem.uwec.edu/Chem454_S08/MetabolicchartBig.pdf

G, Free Energy, recall:G = ΔG° + RT ln[C]c [D]d

[A]a [B]baA + bB cC + dD

0 = ΔG° + RT ln[C]c [D]d

[A]a [B]b

G° = - RT ln[C]c [D]d

[A]a [B]b

G° = - RT ln Keq

For biochemical reactions, we define a different standard state for the concentration of H+standard state for [H+] = 10-7 M, pH = 7.0this modified standard state is given the symbol G°’

ATP

HHH

O

HO OH

N

N

N

N

NH2

-O-P-O-P-O-P-O-CH2

O

O-

O

O-

O

O-

H

ATP + H2O ADP + Pi + H+

K'eq =[ADP] [Pi] [H+]

[ATP] at pH 7.0 and 25°C

G°' = - (8.31 x 10-3 kJ mol-1) (298 K) ln 2.23 x 105

G°' = -30.5 kJ mol-1 = -7.29 kcal mol-1

the experimental value of K’eq = 2.23 x 105

ATP-Why?ATP + H2O ADP + Pi + H+

resonance

repulsion

BUT,it’s kinetically stable

Other “high energy compounds

"High energy" substance: a thermodynamically unstable substance whose hydrolysis or decomposition can be easily coupled to an unfavorable reaction. The arbitrary cut-off is ~-10kJ/mol. There is no such thing as a "high energy bond" per se.

Coupled ReactionsFree energies are additive; favorable rxns can drive unfavorable;e.g.sequential coupling

A B CK1 K2

K1

=

[ B ]

[ A ]

= 0 . 1

K2

=

[ C ]

[ B ]

= 100

Sequential coupling

acetylCoA Oxaloacetate

Citrate

+ Citryl CoA

CoA-SH+

Simultaneous coupling

A B CK3

+ D+

Example:Glucose to glucose-6-phosphate

glucose Pi glucose-6-phosphateK1

+

ATPK2

ADP Pi+

PEP + H2O Pyuvate+ Pi

ADP + H2OATP +Pi

G°' = -61.9 kJ mol-1

G°' = +30.5 kJ mol-1

Example: calculate G°’ for this reaction involving phosphoenolpyruvate (PEP) and decide whether or not it is spontaneous

use the following information from Table 14.1

Overall Coupling:Glucose to CO2 and H2O

C6H12O6

+

6O2

6CO2 6H2O

-2867

32ADP + 32Pi 32ATP

+

-1891

G°'(kJ mol-1)

C6H1 2O6 6 O2+ 3 2 AP + 3 2 Pi+

+6 CO2 6 H2O

3 2 ATP+

+976

Under aerobic conditions, glucose is oxidized to carbon dioxide and water

the efficiency of the energy conservation under aerobic conditions is approximately 34%

Metabolism concerns how you get from here to there!!

Metabolic strategies-Oxidation(burning of carbon containing compounds)

Substrate level phosphorylations

Ion gradients

Overall Process

Recurring Motifs in Metabolism “Activated” electron and functional group

carriers

Electron Carriers:

NAD+

H:-

Electron Carriers:

FAD

Typical Oxidation Reactions

“Carbon” carriers

Chemical Reaction “themes” in metabolism

Chemical Reaction “themes” in metabolism:Patterns

Factors Affecting Metabolic Rate

• Metabolism operates at a steady state.• Metabolites flow through the steady state

Factors Affecting Metabolic Rate

Factors Affecting Metabolic Rate

• Metabolites flow through the steady state

ATP

Factors Affecting Metabolic Rate

Factors Affecting Metabolic Rate

Factors Affecting Metabolic Flow or flux through pathways

• Amounts of enzymes

• Catalytic activity of enzymes

• Availability of substrates

ATP Balance affects many metabolic pathways

€

EnergyCh arge =[ATP]+ 1

2[ADP]

[ATP]+ [ADP]+ [AMP]

ATP Balance affects many metabolic pathways

CONTROL OF METABOLIC FLUX, J

€

S A BJ J

€

υF

€

υR

P

rate determiningstep

e.g. glucose pyruvate

CONTROL OF METABOLIC FLUX, J

e.g. Substrate Cycling:See glycolysis (F-6-P to F1,6-BP)